I. CATALYTIC ASYMMETRIC BROMO-SPIROLACTONIZATION II. DESIGN AND DEVELOPMENT OF ORGANIC DYES FOR TRANSPARENT LUMINESCENT SOLAR CONCENTRATOR (TLSC) III. DISCOVERY OF A NOVEL CYANINE DEGRADATION PATHWAY By Mehdi Moemeni A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of Chemistry—Doctor of Philosophy 2022 ABSTRACT In Chapter I, a novel enantioselective method has been developed that leads to the formation of a variety of substituted spirolactones. This process furnishes the desired spirolactones in excellent yields and high enantioselectivities. Different categories of acidic and basic chiral catalysts were screened and the lead hit for achieving minimal enantioselectivity was obtained with a cinchona alkaloid derivatized at its C9-OH as a carbamate. With these results, we pursued the synthesis of a library of new catalyst families, in particular urea, thio-urea, carbamate and thio-carbamate systems and investigated them as asymmetric catalysts for the bromo spirolactonization reaction of oxo-alkenyl carboxylic acid substrates. In Chapter II, a variety of near-infrared dyes with high quantum yield and large Stokes shift were synthesized for fabrication of transparent luminescent solar concentrators (TLSC) devices, leading to high power conversion efficiencies. Based on a combined experimental and computational study, a simple strategy for optimizing the Stokes shift in fluorescing cyanines was proposed. As a result, a significant Stokes shift enhancement in cyanine dyes was achieved as a result of C4′-substitution with amines. In Chapter III, we discovered a non-photoactivated, oxygen-free, thermal degradation of cyanine dyes. Reaction optimization led to the developing of a new method for converting cyanines to truncated symmetric and asymmetric derivatives with high efficiency. We later used deuterium label tracing studies and deuterium exchange studies in addition to other supporting experiments to propose a mechanism for these transformations. Dedicated to my parents, my family and Rahele for their endless love and support iii ACKNOWLEDGMENTS First, I would like to express my sincere gratitude and appreciation to my Ph.D. advisor, professor Babak Borhan for his understanding, endless support, motivation and kind guidance. I am really grateful to him for welcoming me to his research group and helping me through my projects while giving me the freedom to come up with new ideas and enjoy my chemistry. He is an amazing friend and accepted his students as his family and invited us for Thanksgiving, Christmas and New Year. We had great times in summer group camping, soccer games, fireworks on the 4th of July, and birthday cakes parties for everyone. Thanks for advising me both in my research and as well as on my career. I am greatly thankful to my committee member, Professor James Jackson, Professor Xuefei Huang and Professor James Geiger, for their time, patience, support and guidance during my PhD program. I would like to thank all my lab members, for their amazing friendship, help and support. I especially want to express my appreciation and gratitude to Dr. Chrysoula Vasileiou, for her endless help. The past members of Borhan group, especially Dr. Wei Sheng, Dr. Hadi Gholami, Dr. Bardia Soltanzadeh, Dr. Jun Zhang, Dr. Setare Tahmasebi Nick, Dr. Daniel Steigerwald and Dr. Debarshi Chakraborty for teaching me their skills and sharing their valuable knowledge and experience. I am very grateful to the current and former members of Borhan group that I have had the chance to work with them, especially Aria Vahdani, for working with me and helping me with multiple projects. I would also like to thank my amazing collaborators: Professor Richard Lunt, Professor Gary Blanchard, Professor James Jackson, Professor Marcos Dantus, iv Professor Benjamin Levine, Professor Piotr Piecuch, Dr. Chenchen Yang, Dr. Jurick Lahiri, Dr. Briana Capistran, Dr. Ilias Magoulas, Dr. Stephen Yuwono, Dr. Matthew Bates, Chris Herrera, Fangchun Liang and Andrew Wendel. I would like to extend my sincere gratitude to the MSU facility’s leads, Dr. Daniel Holmes (NMR), Dr. Richard Staples (Crystallography) and Dr. Tony Schilmiller (Mass Spectrometry). I want to deeply thank my family, especially my parents for their endless love, patience, support and encouragement. They spent countless times helping me during my education, and I will be forever grateful. Finally, I want to thank the most important person in my life, Rahele my beloved wife. It is impossible to use words to describe how thankful I am to her. During these years in graduate school, I had many ups and downs, and she always was there to support me and cheer me up. She has been my driving force to wake up every morning from the first day I met her, and I couldn’t want anything more than to work with her in the same lab and share all moments together. I definitely would not be standing here if it was not because of her love and encouragement. I dedicate this milestone to my best friend, Rahele. v TABLE OF CONTENTS LIST OF TABLES………………………………………………………………….…………. vii LIST OF FIGURES……………………………………………………………………….…… ix LIST OF SYMBOLS AND ABBREVIATIONS……………………………..…………...… xiv Chapter I: Catalytic Asymmetric Bromo-Spirolactonization ...................................... 1 I-1 Introduction; structural features of the spirolactone moiety ......................................... 2 I-2 Chemical synthesis of spirolactones (previous approaches) ...................................... 3 I-3 Development of halenium initiated spirolactonization ................................................. 5 I-4 Development of asymmetric bromospirolactonization ............................................... 12 I-5 Future work ............................................................................................................... 34 I-6 Experimental section ................................................................................................. 39 REFERENCES ............................................................................................................... 95 Chapter II: Design and Development of Organic Dyes for Transparent Luminescent Solar Concentrators (TLSCs) ............................................................. 100 II-1 Introduction of transparent luminescent solar concentrators (TLSCs) ................... 101 II-2 Important parameters for investigating TLSC devices ........................................... 102 II-3 Development of organic dyes for use with TLSC devices ...................................... 104 II-4 Future work ............................................................................................................ 137 II-5 Experimental section .............................................................................................. 140 REFERENCES ............................................................................................................. 194 Chapter III: Discovery of a Novel Cyanine Degradation Pathway .......................... 199 III-1 Introduction to cyanine fluorescent dyes ............................................................... 200 III-2 Photo-degradation pathways of cyanine dyes ...................................................... 201 III-3 Discovery and development of a non-photoactivated, oxygen-free degradation of cyanine dyes. ............................................................................................................... 205 III-4 Experimental section ............................................................................................. 231 REFERENCES ............................................................................................................. 251 vi LIST OF TABLES Table I-1. Reaction optimization for improving the diastereoselectivity of spirolactonization ............................................................................................................ 14 Table I-2. Asymmetric bromospirolatonization with basic catalysts ............................... 18 Table I-3. Reaction optimization for cat. I-51; temperature, solvent and Br source were altered ............................................................................................................................ 19 Table I-4. Study of the effects of different carbonyl linkers on asymmetric bromospirolatonization ................................................................................................... 22 Table I-5. Reaction optimization for cat. I-54; temperature, solvent and Br source were altered ............................................................................................................................ 23 Table I-6. Catalyst optimization; study of electronic effect on the carbamate aryl group .............................................................................................................................. 25 Table I-7. Catalyst optimization; electronic and steric effect on aryl carbamate and quinoline ......................................................................................................................... 26 Table I-8. Study of thiourea, urea and carbamate catalysts .......................................... 28 Table I-9. Grubbs cross metathesis results ................................................................... 31 Table I-10. Substrate scope study of uncatalyzed bromospirolactonizations ................ 32 Table I-11. Substrate scope study of catalytic asymmetric bromospirolactonizations ... 34 Table II-1. Strategy toward large Stokes shift cyanine dyes ........................................ 107 Table II-2. Spectroscopic data of amine substituted heptamethine cyanines .............. 111 Table II-3. Spectroscopic data of dye II-13 in different solvents .................................. 113 Table II-4. Spectroscopic data of amine substituted ICG based cyanine dyes ............ 115 Table II-5. Structure and spectroscopic data of amine substituted benzothiazole based cyanines ....................................................................................................................... 116 Table II-6. Important geometric parameters that determine the electronic character (bis- dipolar vs. cyanine-like) of the five structures in the parallel conformationa ................. 123 Table II-7. Spectroscopic properties and TLSC photovoltaic parameters of COi8DFIC ..................................................................................................................... 131 vii Table II-8. Spectroscopic properties and TLSC photovoltaic parameters of COi8DFIC ..................................................................................................................... 136 Table II- 9. Absolute energies of optimized geometries on the DFT level of theory. (CAM- B3LYP/6-31G*) ............................................................................................................. 168 Table II-10. Important geometric parameters for CAM-B3LYP/6-31G* structuresa..... 169 Table III-1. Reaction optimization with secondary amine ............................................. 209 Table III-2. Reaction optimization with tertiary amine .................................................. 211 viii LIST OF FIGURES Figure I-1. Spirolactone moiety embedded in the structure of natural products. ............. 2 Figure I-2. Spirolactonization via photo-oxidation of hydroxyalkyl furans ........................ 3 Figure I-3. Spirolactonization via palladium catalized CO insersion ................................ 4 Figure I-4. Rodriguez’s approach to access the enantioselective spirolactones ............. 5 Figure I-5. Yeung’s approach to access the enantioselective spirolactones ................... 5 Figure I-6. Glossary of our published enantioselective chlorocyclization methodologies .................................................................................................................. 6 Figure I-7. Two possible TS (classic vs NAAA) for chlorolactonizations ......................... 7 Figure I-8. Strategies towards diastereoselective bromospiroketalization. ...................... 8 Figure I-9. Bromocyclization of I-38 yields the macrocyclic bromoether as the major product ............................................................................................................................. 9 Figure I-10. Substrate I-40-THP furnished the desired bromospiroketal I-37 as a single isomer ............................................................................................................................. 10 Figure I-11. Diastereoselective dibromospiroketalization .............................................. 11 Figure I-12. Enantioselective bromo spiroketalization with vaulted biaryl catalysts ...... 12 Figure I-13. Strategy towards diastereoselective bromospirolactonization ................... 13 Figure I-14. Bromospirolactonization results; X-ray crystal structure of I-46a and I-46b ........................................................................................................................ 13 Figure I-15. Diastereselectivity study in the presence of acid ....................................... 15 Figure I-16. Asymmetric bromospirolactonization with acidic catalysts; TS in dashed box .................................................................................................................................. 16 Figure I-17. Generalized structures for basic catalysts based on the cinchona alkaloid structure.......................................................................................................................... 19 Figure I-18. General synthesis of basic catalysts .......................................................... 21 Figure I-19. Synthetic methods for making substrates .................................................. 30 Figure I-20. X-ray crystal structure of I-99a ................................................................... 33 ix Figure I-21. Development of di-bromo and di-halospirolactonization ............................ 35 Figure I-22. Proposed total syntheses of obtusallenes VI ............................................. 37 Figure I-23. X-ray structure of I-46a (different views) .................................................... 81 Figure I-24. X-ray structure of I-46b (different views) .................................................... 85 Figure I-25. X-ray structure of I-100 (different views) .................................................... 89 Figure I-26. X-ray structure of I-99a (different views) .................................................... 94 Figure II-1. A. TLSC model that both UV and NIR light could absorb while visible light passing through. B. Spectra of chromophore; S stand for Stokes shift, W is the width of emission peak (Permission to reproduce this figure is kindly provided by Prof. Lunt and Dr. Yang) ...................................................................................................................... 101 Figure II-2 A. Examples of J-V curves for two different solar cells. B. External quantum efficiency spectra of a silicon and GaAs PV cells (Permission to reproduce this figure is kindly provided by Prof. Lunt and Dr. Yang). ................................................................ 104 Figure II-3. LSC system as a function of calculated Stokes shift (Permission to reproduce this figure is kindly provided by Prof. Lunt and Dr. Yang) ............................................ 105 Figure II-4. Correlation of Stokes shift and self-quenching .......................................... 106 Figure II-5. Bis-dipole structure of substituted cyanines .............................................. 108 Figure II-6. Synthesis of heptamethine cyanine dyes .................................................. 109 Figure II-7. Synthesis of first series of amine substituted heptamethine cyanine dyes .............................................................................................................................. 110 Figure II-8. Normalized absorption and fluorescence emission spectra (measured in DCM) for dyes II-10 (top left) and II-12 (top right), and dyes II-14 (bottom left) and II-15 (bottom right). ............................................................................................................... 112 Figure II-9. Structure of second series of amine substituted heptamethine cyanine dyes .............................................................................................................................. 114 Figure II-10. Generalized cyanine-like and bis-dipolar structures of cyanine dyes ..... 118 Figure II-11. Scatter plot of the experimental spectral energy maxima as a function of the DFT-computed theoretical excitation energies. Absorption and emission energies are shown by blue and red dots, respectively. The lowest energy conformer is chosen for II- 9 – II-14 and II-16, while for II-15, both the parallel (II-15∥) and perpendicular (II-15⟂) conformers are shown. ................................................................................................. 120 x Figure II-12. Scatter plot of the experimental spectral energy maxima as a function of the DFT-optimized bond length alternation coordinate (in angstrom). Absorption and emission energies are shown by blue and red dots, respectively. ............................... 121 Figure II-13. Broad absorbing spectra leads to harvesting higher photon numbers .... 125 Figure II-14. Structures of D-A-D dyes; DRCN7T and COi8DFIC ............................... 127 Figure II-15. Synthesis steps of COi8DFIC .................................................................. 128 Figure II-16. Data for COi8DFIC; a. Normalized absorption and emission spectra of in chlorobenzene solution, b. Normalized absorption and emission spectra of in polymer matrix, c. Current density versus voltage (J–V) characteristics of TLSCs with different concentrations, d. Average EQELSC(λ) spectra of TLSCs with different concentrations, e. Photographs of all the TLSC devices. (Permission to utilize the Spartan helmet logo is kindly provided by MSU.) ............................................................................................. 130 Figure II-17. Schematic of the working principle of the dual-band selective harvesting TLSC. ........................................................................................................................... 133 Figure II-18. Molecular structure, normalized absorption and emission spectra of Cs2Mo6I8(CF3CF2COO)6 nanocluster ........................................................................... 134 Figure II-19. Molecular structure, normalized absorption and emission spectra of BODIPY ........................................................................................................................ 135 Figure II-20. a. J–V characteristics of TLSCs, b. Average EQELSC(λ) spectra of TLSCs........................................................................................................................... 135 Figure II-21. a. Amine C2-substituted cyanines, b. asymmetric cyclized aminated cyanine ......................................................................................................................... 137 Figure II-22. Proposed head groups to redshift the Cy5 core and, proposed new Cy5 structures ...................................................................................................................... 138 Figure II-23. General structure of D–A–D NIR I/II fluorophores ................................... 139 Figure II-24. Scatter plot of the experimental spectral energy maxima as a function of the DFT-optimized bond length alternation coordinate (in angstrom). Absorption and emission energies are shown by blue and red dots, respectively. ............................... 167 Figure III-1. Structure of famous cyanine dyes ............................................................ 200 Figure III-2. Cyanine photolysis products .................................................................... 201 Figure III-3. Mechanism and degradation products of cyanine photooxidation ........... 202 xi Figure III-4. Photoblueing results from two carbon truncation ..................................... 203 Figure III-5. Photodegradation mechanism (by Schnermann and co-workers) ........... 204 Figure III-6. Photodegradation mechanism (by Lee and co-workers) .......................... 205 Figure III-7. A. Amination at C4′ for tuning the Stokes shift, B. Amination at C3′ resulted in corresponding Cy5 and As-Cy5 derivatives ............................................................. 206 Figure III-8. General synthesis of heptamethine cyanines .......................................... 207 Figure III-9. Study the conversions on Cy7 to investigate the generality of this reaction ......................................................................................................................... 208 Figure III-10. Identified compounds from cyanine truncation with secondary amine ... 210 Figure III-11. Conversion of Cy7.5 in the presence of tertiary amine (DIPEA) ............ 213 Figure III-12. Conversion of di-substituted cyanine ..................................................... 213 Figure III-13. Normalized absorption and emission of all cyanine’s degradation fragments...................................................................................................................... 214 Figure III-14. A. Synthesis of Cy7-D5, B. Conversion of deuterated Cy7 with secondary amine ............................................................................................................................ 218 Figure III-15. A. Deuterium exchange in D2O, B. Deuterium exchange in D2O and DIPEA ........................................................................................................................... 219 Figure III-16. Proposed mechanism of cyanine conversion with secondary amines ... 221 Figure III-17. Conversion of deutrated Cy7 with tertiary amine (DIPEA) ..................... 221 Figure III-18. Recombinative chain shortening ............................................................ 222 Figure III-19. Proposed mechanism of cyanine conversion with tertiary amines ......... 224 Figure III-20. Proposed mechanism of Cy7 conversion to Cy3 ................................... 225 Figure III-21. Cy7 reaction with; A. neutralized head group, B. charged head group ............................................................................................................................ 225 Figure III-22. Cy5 conversion reactions failed in different conditions .......................... 226 Figure III-23. Optimized cyanine conversion reactions ................................................ 227 Figure III-24. top: Normalized absorptions (in DCM), bottom: Normalized emissions (in DCM) ............................................................................................................................ 228 xii Figure III-25. Cyanine structures for stability study ..................................................... 229 xiii LIST OF SYMBOLS AND ABBREVIATIONS lem emission wavelength lmax absorption wavelength < less than > larger than Å angstrom ACN acetonitrile Ar aryl As-Cy asymmetric cyanine AVT average visible transmittance Bn benzyl BODIPY boron-dipyrromethene CaH2 calcium hydride CDCl3 deuterated chloroform CHCl3 chloroform cm-1 wavenumber Cy cyanine d doublet DBDMH 1,3-dibromo-5,5-dimethylhydantoin DCDMH 1,3-dichloro-5,5-dimethylhydantoin DCM dichloromethane DFT density functional theory xiv DIBAL-H diisobutylaluminium hydride DMF dimethylformamide DMSO dimethyl sulfoxide ee enantiomeric excess EQE(λ) external quantum efficiency spectrum equiv. equivalent er diastereomeric ratio ESI electrospray Ionization Et3N triethylamine EtOH ethanol FF fill factor of a solar cell g gram h hour Hal A halenium affinity HCl hydrochloric acid HPLC high pressure liquid chromatography HRMS high resolution mass spectrometry Hz hertz i-Pr isopropyl IQE internal quantum efficiency IR infrared ISC short-circuit current xv J current density J NMR coupling constant J-V current density-voltage characteristic KOH potassium hydroxide M molar m multiple MeOH methanol mg milligram MgSO4 magnesium sulfate min minute mmol millimole N.R. No Reaction Na2SO4 sodium sulfate NAAA nucleophile assisted alkene activation NaH sodium hydride NaOH sodium hydroxide NBS N-bromosuccinimide nBuLi n-butyllithium NC nanocluster NCS N-chlorosuccinimide NIR near-infrared nm nanometer xvi NMR nuclear magnetic resonance PCE power conversion efficiency PV photovoltaic q quartet QY quantum yield r.t. room temperature SS Stokes shift t triplet TFA trifluoroacetic acid THF tetrahydrofuran TLC thin layer chromatography TLSC transparent luminescent solar concentrator UV ultraviolet UV-Vis ultraviolet-visible δ chemical shift ε molar absorption coefficient xvii Chapter I: Catalytic Asymmetric Bromo-Spirolactonization 1 I-1 Introduction; structural features of the spirolactone moiety The spirolactone moiety is a key skeletal unit of a number of biologically active natural products. Examples vary from the simple Massarinolin A and its analogs1 with antibacterial activity against drug-resistant strains to the structurally complex compounds Lancifodilactone G2 and Phainanoid F3 that show anti-HIV and immunosuppressive activity, respectively. Most spirolactone motifs found in natural products contain [5,5], [5,6], [6,5] and [6,6] rings with different biological properties (Figure I-1). The spirolactones considered here are a subset of the spiroketal family with an ester functional group in one of the spiro rings. O O O O HO O O O O H H O Abiespirones a I-2 Terreolide E I-3 O ROS scavenger mushroom toxin [5,5] [6,6] O O O ( )n ( )m Spirolactones I-1 OH Pseudolarolide H I-4 Soladulcoside A I-5 OH antimicrobial anti-tumor [6,5] [5,6] OH O O O H H O H O H O O O O H O H OH H O H OH O OH HO OH Figure I-1. Spirolactone moiety embedded in the structure of natural products Spirolactones’ biological applications and structural designs have attracted a large number of synthetic discoveries over the past few decades. In this vein, several approaches for the synthesis of racemic spirolactones have been reported.4-9 However, 2 stereoselective approaches for the synthesis of these motifs is still under development. Inspired by our success in asymmetric halofunctionalization of olefins, we aimed to develop a novel catalytic asymmetric method to furnish enantioselectively halogenated spirolactones. I-2 Chemical synthesis of spirolactones (previous approaches) Oxaspirolactones were synthesized for the first time in 1979 by Mitsunobu and co- workers.10 The photo-oxidation of hydroxyalkyl furans by Rose Bengal and oxygen, followed by attack with hydroxyl, resulted in the formation of the corresponding spirolactone. (Figure I-2). hv, O2 HO Rose Bengal R O O O O R I-6 I-9 1O 2 [4+2] dehydration HO Intramolecular O ring opening R O O OOH R O I-7 I-8 O Figure I-2. Spirolactonization via photo-oxidation of hydroxyalkyl furans Since then, different groups have reported the racemic reactions for synthesis of oxaspirolactone through different mechanisms such as retro-aldol rearrangement, Wittig olefination, acid catalyzed spirolactonization, etc.4, 7, 9, 11, 12 One of the most recent approaches to access these motifs is the palladium-catalyzed cascade carbonylative cyclization, which was reported by Dai and co-workers.5 The mechanism goes through a 3 palladium C-C cleavage, followed by ketal formation and CO insertion which finally undergoes the lactonization to form the oxaspirolactone structure (Figure I-3). O O O Pd(II) cat., CO (g) HO ( )n OH oxidant ( )n I-10 I-14 C-C [O] Pd(II) Pd(0) cleavage lactonization O Pd(II) O O Pd(II) O O Pd HO O ( )n ( )n ( )n I-11 ketal formation I-12 CO insertion I-13 Figure I-3. Spirolactonization via palladium catalized CO insersion In terms of enantioselective approaches, there are only two examples, both of which have significant substrate bias. The first one was reported in 2013 by Rodriguez and co-workers. There an aminated spirolactone was formed by an asymmetric [3+2] reaction in the presence of BINOL-based chiral phosphoric acid and gold catalysts13 (Figure I-4). Primary aryl amines are obligatory starting material for this reaction. The second approach, published in 2020 by Yeung and co-workers, synthesized a phenyl substituted spirolactone through an asymmetric domino halocyclization of olefinic keto- acids. An electron-rich amino-thiourea catalyzed this transformation with high enantioselectivity14 (Figure I-5). All of the substrates studied in this work have the (vinylbenzoyl)benzoic acid core, which would result only in 5,5- bis-phenyl substituted spirolactones. 4 OH HO O (JohnPhos)AuMe O O O H2NAr R XH I-16 O NHAr I-15 I-17 16 examplex I-20 O O 82-99% Yield P up to 98:2% er O OH up to 7:1 dr cycloisomerization asymmetric R and condensation [3+2] HO O R = 9-anthracenyl O I-21 NAr I-18 I-19 Figure I-4. Rodriguez’s approach to access the enantioselective spirolactones X O COOH X H O Cat. (10 mol%) O N O CHCl3/Hexane (1:2) O -78 ºC O I-22 I-23 I-25 O O 37 examples with different X S up to 93% Yield > 99.5:0.5% er N N > 99:1 dr H H I-24 N O R R electron-rich amino-thiourea catalyst Figure I-5. Yeung’s approach to access the enantioselective spirolactones I-3 Development of halenium initiated spirolactonization Our strategy toward the synthesis of spirolactones originated from our group’s efforts towards the halofunctionalization of olefins. A summary of our asymmetric halofunctionalization methods is shown in Figure I-6. In 2010, our group reported the first asymmetric chlorofunctionalization of olefins15. The Sharpless ligand (DHQD)2PHAL was discovered to be the preferred catalyst for the enantioselective chlorocyclization of 4-aryl- 4-pentenoic acids in the presence of 1,3-dichloro-5,5-diphenylhydantoin (DCDPH) as the terminal chlorenium source. The generality of this condition to promote enantioselective 5 halocyclization of other substrates was then evaluated. This effort showed that unsaturated amides could be chlorocyclized using similar reaction conditions to give access to chiral halogenated oxazoline products.16 Intriguingly, implementation of an unsaturated carbamate led to the development of a solvent-dependent enantiodivergent reaction whereby either enantiomer of the product could be accessed using the same catalyst by simply changing the reaction solvent.17 R/Ar O O Cl I-28 CO2H R2 O Ar/R I-27 Ar R1 N Ar I-29 H O N O R2 N N R1 I-30 O O Cl N N Cl Cl H H N N O O O R O R N Ar Ar R = Ph: DCDPH H N N R = Me: DCDMH Ar I-31 (DHQD)2PHAL (I-26) O N Cl H I-32 N O Ar n-PrOH R/Ar CHCl3-Hex O I-33 O O O NH O NH Cl R/Ar I-34 I-35 R/Ar Cl Figure I-6. Glossary of our published enantioselective chlorocyclization methodologies The study of the mechanism of chlorolactonizations of olefins prompted the development of new concepts to be able define the transition state structures for this chemistry. The halenium affinity scale (HalA) was developed to introduce a thermodynamic measure that quantifies the donor/acceptor interaction with the halenium 6 that is being transferred.18 The HalA values of numerous molecules were reported, and their patterns were experimentally verified through NMR studies, supporting the concept of HalA-guided predictive reactivity. Examination of the HalA of olefins and halogenation species showed that the classical stepwise reaction mechanism of electrophilic addition to alkenes would not lead to formation of the observed products. This resulted in the discovery of the role of nucleophiles in halofunctionalization reactions. We found a direct and strong correlation between the strength of the nucleophile and rate of halofunctionalization, which led to the proposal of the Nucleophile Assisted Alkene Activation (NAAA) concept.19 HalA(Cl) 173.6 kcal/mol O Cl N N Cl 1.9 Å O O O HO2C 4.2 Å Ph Cl HalA(Cl) 167.4 kcal/mol TS1-Classic HalA(Cl) 173.6 kcal/mol O Cl N N Cl O O O O δ+ O H Ph Cl δ– HalA(Cl) 173.3 kcal/mol TS2-NAAA Figure I-7. Two possible TS (classic vs NAAA) for chlorolactonizations 7 As shown in Figure I-7, the calculation of the transition state does not lead to a Cl+ transfer in the classical transition state picture (TS1) since the HalA of the double bond is 167.4 kcal/mol: around 6 kcal/mol less that of than our halogen donor DCDMH. The HalA values indicate that the halogen would prefer to remain on DCDMH, rather than to transfer to the nucleophile. However, in the NAAA figure, the carboxylic acid adds in a concerted manner with the halenium to the olefin, leading to an increase of the olefin’s HalA, enabling it to compete with the halogen donor (TS2). The interaction of the carboxylic acid group leads to an increase of HalA (173.3 kcal/mol), approaching the HalA of DCDMH anion (173.6 kcal/mol). The NAAA concept has guided us in reaction design and more recently we reported, a diastereoselective halenium initiated bromo- and dibromospiroketalization method20. A plethora of structurally diverse bioactive natural products reveals the spiroketal moiety. Not surprisingly, their biochemical properties have attracted a great deal of synthetic exploration over the past few decades. In this vein, several elegant strategies towards stereoselective construction of spiroketal cores have been reported. In contrast to approaches that focus on controlling the stereoselectivity in the ketalization - Aδ ‡ R2 O TS-1 A-Br Br Br (Br+ source) Ph O R1 O R1 δ+ O R2 O PG-O ( )n ( )n PG (n = 0,1) (n = 0,1) I-36 I-37 Figure I-8. Strategies towards diastereoselective bromospiroketalization event21-23 our work was based on exploiting the thermodynamics associated with the transition state (TS) in halofunctionalization of olefin I-36 (see TS-1, Figure I-8). Owing to 8 the weak nucleophilicity of the templated ketone, interception of the halenium atom by the activated olefin in I-36 will transpire putatively via a late transition state. In the proposed asynchronous concerted addition (Ade3), it is anticipated that stereospecificity will be defined by the templating group (-OPG), engaged in enhancing the nucleophilic character of the ketone in the incipient oxocarbenium. Initial HalA(Br) guided optimizations revealed 3-bromo-1-chloro-5,5-dimethylhydantoin (BCDMH) as an ideal bromenium source generated in situ by combining equimolar amounts of DBDMH and DCDMH. O DCDMH, DBDMH Br Ph O Br Ph (1 equiv each) Ph O O O I-38 HO toluene, 4 h, I-37 I-39 rt, 89% (1:3) -AH -AH δ- ‡ δ- ‡ Ph O A δ+ A H O H I-38a Br Br (A–Br) Ph O Ph O minor O δ+ O H TS-1 TS-2 Ph O O O O I-38b OH Br N N Br Cl N N Cl Cl N N Br major disproportionation O O O mixture of hemiketals DBDMH DCDMH Figure I-9. Bromocyclization of I-38 yields the macrocyclic bromoether as the major product Substrate I-38, which exists in equilibrium with the corresponding hemiketals, reveals either an alkene proximal ether moiety in I-38a or the hydroxyl moiety in I-38b, poised for pre-polarization of the alkene (Figure I-9). Surprisingly, bromofunctionalization 9 of I-38 furnished the macrocyclic bromoether I-39 as a major product (>98:2 dr), indicating a conformational preference of the hemiketal intermediate, kinetically biased towards I- 38a. As anticipated from the HalA(Br) values, substrate I-40-THP furnished the desired bromospiroketal I-37 as a single isomer (Figure I-10). The generality of this transformation was evaluated with a variety of substrates, and good to excellent yields and drs were obtained. O Br DCDMH, DBDMH Ph O Ph >99% yield, I-37 O >98:2 dr toluene, 3 h, rt THPO EtOH (10.0 equiv) I-40 -AH (A–Br) -EtOTHP δ- A ‡ δ- Br Ph O Ph O δ+ δ+ O O THP THP TS nucleophile assisted asynchronous concerted pre-polarization cyclization Figure I-10. Substrate I-40-THP furnished the desired bromospiroketal I-37 as a single isomer To access the dibromo- spiroketal scaffold of natural products, we initially exploited the stereoelectronics associated with the six- membered oxocarbenium ion, using a variety of keto- alkenols. As it shown in Figure I-11, when ethanol was omitted from the reaction mixture to avoid the early trans-ketalization of tetrahydropyranyl from intermediate-(I), the templated oxocarbenium underwent rapid conversion to enol ether (II) via deprotonation at the β-carbon (C3). A pseudo- axial capture of another bromenium 10 ion by the nucleophilic olefin in (II) did eventually yield the dibromo-spiroketal. Unexpectedly, inclusion of water from conc. HCl facilitates the removal of THP group. HCl was necessary to effect the desired transformation. With the oxocarbenium intermediate embedded in a six- membered ring, dibromospiroketals were obtained in good yields and diastereoselectivities. Br R2 O NBS (2.5 equiv) 12 M HCl Br R1 O R1 OTHP >88% yield, I-41 CHCl3, 2 h, rt R 2 O >98:2 dr I-42 (A-Br) -AH δ- -EtOTHP A ‡ A A Br Br Br H R1 O 5 3 5 Br Br -H Br R1 O R 2 δ+ O R1 O O 3 THP R1 R2 O R2 O THP THP R2 TS (I) (II) (III) concerted cyclization pseudo-axial attack Figure I-11. Diastereoselective dibromospiroketalization Our group’s attempts to develop an enantioselective version of the bromospiroketalization failed with (DHQD)2PHAL (cinchona alkaloid dimers). This motivated us to evaluate a new Brønsted acid/Lewis base catalytic system. To this aim, we investigated the Vanol- Imidodiphosphoramide type catalysts. The initial data showed the dihedral angle (the angle between the substituents at the 7,7’-positions on each VANOL ligands of the catalyst), plays a critical role in enantioinduction (dashed box in Figure I-12). This angle depends on the nature of the 7,7’-substituents, and further studies indicated that an adamantyl group at these positions induced the highest enantioselectivity in the asymmetric bromospiroketalization reaction (Figure I-12). In this 11 recent work, the generality of this enantioselective transformation was evaluated for different substrates, and good to excellent yields and enantiomeric ratios (er) were obtained. O Cat. (10 mol%) Br DBDMH (1.2 equiv.) Ph O Ph PhCH3, -50 °C O I-37 THPO 30 h, 87% I-40 93:7 er >98:2 dr R Tf Tf R dihedral angle HN N Ad θ Ad P P O N O O O Ad R R Ph Ad PhPh Ph I-42-Cat. R = adamantyl Figure I-12. Enantioselective bromo spiroketalization with vaulted biaryl catalysts I-4 Development of asymmetric bromospirolactonization We sought to further extend our methodology by replacing THP protected alcohols with carboxylic acids. We planned to take advantage of halofunctionalization of olefins, with the intention of generating the valuable spirolactone moiety which, as previously mentioned, is a key skeletal moiety found in a number of biologically active natural products. Based on our previous studies, we envisioned that unsaturated substrate I-48 would undergo bromofunctionalization followed by nucleophilic attack of the ketone, resulting in the formation of the oxacarbenium. Upon generation of the oxacarbenium, subsequent trapping by the carboxylic acid would furnish the spirolactone (Figure I-13). 12 A R2 O A-Br Br O Br (Br+ source) R1 R1 O OH δ+ R1 R2 O R2 O O H I-43 O I-44 O Figure I-13. Strategy towards diastereoselective bromospirolactonization As illustrated in Figure I-14, our initial study for the uncatalyzed reaction exhibited excellent yields (up to 92%) and moderate diastereoselectivity (2.5:1) for 6,5-bromo spirolactones. O Br NBS (1.1 equiv.) Ph O Br OH Ph O O Ph O + O PhMe, 1 h, rt. O 92%, 2.5:1 dr I-46a O I-45 I-46b I-46a I-46b Figure I-14. Bromospirolactonization results; X-ray crystal structure of I-46a and I-46b The reaction showed similar results with different bromine sources (NBS, DBDMH, DBDPH, and BCDMH). The relative stereochemistry of halogenated spirolactone products was established by X-ray crystal structure. The directed diastereoselectivity stems from the direction of attacking acid relative to the ketone. Attempts toward improving the diastereoselectivity are listed in Table I-1. The effects of temperature, solvent and various halogen sources were examined. 13 Table I-1. Reaction optimization for improving the diastereoselectivity of spirolactonization O X Ph O X X source (1 equiv) Ph O O OH + Ph O O Solvent (0.05 M) O a b I-45 Temp.; 20-60 min O Entry Halenium Source Solvent Temperature dra (a:b) 1b BCDMH Toluene r.t. 1.5:1 2b BCDMH Toluene 0 °C 1.6:1 3 NBS Toluene r.t. 2.5:1 4c NBS Toluene 0 °C 1.3:1 5 NBS Toluene 50 °C 4:1 6 NBS EtOH r.t. 1.2:1 7 NBS CHCl3 r.t. 1:1.2 8 NBS CHCl3/EtOH r.t. 1.8:1 9c DCDMH Toluene r.t. 1:1 10c DCDMH CHCl3 r.t. 1.6:1 [a] drs were estimated by 1H NMR (500 MHz) analysis. [b] BCDMH generated in situ by combining 1 equivalent of each DBDMH and DCDMH, [c] reaction did not complete in 1 hour. The results indicate that the halenium source does not affect the dr ratio, while higher temperatures (50 °C), increase the diastereoselectivity to 4:1 (entry 5). We then focused on the reversible ring opening of the oxaspirolactone motif under acidic conditions. As shown in Figure I-15a, running the bromospirolactonization reaction under the same conditions with a catalytic amount of HCl (12N), led to complete 14 diastereoselective conversion. We envisioned that acid would play a role after the formation of products, and to confirm our hypothesis, a 1:1 mixture of the two diastereomers were treated with a catalytic amount of acid in toluene. After one hour, the 1H NMR showed a single diastereomer (a) in the reaction, which reaffirmed the complete conversion of b to a under acidic condition (Figure I-15). In the presence of acid, the oxygen atom opens the lactone ring, resulting in the oxacarbonium intermediate. Subsequently, the nucleophilic carboxylic acid could then attack from either axial or equatorial direction, with the axial product favored as anticipated due to the anomeric stabilization. (Figure I-15b). a. acid mediated bromospirolactonization O NBS (1.1 equiv.) Br HCl (0.02 N in PhMe) Ph O OH Ph O PhMe, 1 h, rt. I-45 O I-46a O b. proposed mechanism Br HCl Br Ph O Br Ph O Ph O O (0.02 N in PhMe) O O O a b a O O H H Br Br Ph O O Ph O OH HO O Figure I-15. Diastereselectivity study in the presence of acid We started our investigation of the stereoselective bromospirolactonization reaction with acidic catalysts, since they were previously shown to induce excellent 15 enantioselectivity in the case of bromospiroketalization. The reactions carried out with different acid catalysts, are shown in Figure I-16. The reaction with aryl-substituted (S)- VANOL phosphoric acid catalyst I-47, showed no enantiomeric excess (50:50% er) and a 2.5:1 diastereomeric ratio. Studying the reaction with the adamantyl substituted vaulted biaryl catalyst I-42, previously shown to be successful for the enantioselective bromo- spiroketalization reaction, led to improvement of the diastereoselectivity to >10:1, but no enantiomeric excess was observed in this reaction. Also, the rate of the reaction for phosphoric acid catalysts did not differ compared to the uncatalyzed reaction, while the vaulted biaryl catalyst provided a slight improvement in the reaction rate. O NBS (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O PhMe (0.05 M) I-45 O 0 °C; 6 h I-46a O I-46b R2 R Tf Tf R δ- A ‡ HN N Br O O R1 P Ph O P O P R1 N O O OH O O δ+ O H R2 R R O Ph PhPh Ph I-48 I-47 I-42 R1=phenyl R = adamantyl In the presence of basic catalyst, R2=4-tBu-C6H4 >10:1 dr nucleophile-assisted alkene 2.5:1 dr 50:50 er activation (NAAA) is effective 50:50 er Figure I-16. Asymmetric bromospirolactonization with acidic catalysts; TS in dashed box Perhaps, the weak nucleophilicity of the carboxylic acid group, especially under acidic conditions, does not promote the formation of the proposed intermediate (see I-48, Figure I-16). NAAA activation of the olefin would seemingly be more effective in the 16 presence of basic catalyst. Based on these results, we began to investigate a series of basic catalysts. From this investigation we found an interesting result from our previous cinchona alkaloid dimers. As shown in Table I-2, the studies were performed at – 40 °C, since background reactions are effectively suppressed at this temperature. Although (DHQD)2PHAL did not induce chirality in the reaction, it did highly accelerate the rate of the reaction relative to the uncatalyzed version. It led to good yield (82%) with 2:1 diastereomeric ratio and 55:45 enantiomeric ratio. Optimization of the reaction with (DHQD)2PHAL with different temperatures and a variety of solvents resulted in good yield (73-84%) and almost analogous dr (2:1), but no significant improvement in er was observed. To narrow down which component of (DHQD)2PHAL is catalyzing the reaction we truncated the structure it into its constituent components, and ran the reaction with only DHQD as the catalyst. The reaction proceeded with comparable rate and yield. At this point, we realized the need to introduce a handle to our catalyst to induce facial selectivity. Inspired by previous halolactonizations,24 we designed and synthesized a thiocarbamate cinchona derivative catalyst I-51. Applying this catalyst in the same conditions led to 69:31 er, providing a promising start for further structural optimizations (see Table I-2, entry 4). 17 Table I-2. Asymmetric bromospirolatonization with basic catalysts O Br source (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O Solvent (0.03 M) I-45 O Temp.; 24 h I-46a O I-46b Entry Cat. Br Source Solvent Temp. Yield (%) dra (a:b) erb (%) 1 - NBS PhMe:CHCl3 (2:1) -40 °C N.R. - - 2 I-49 NBS PhMe:CHCl3 (2:1) -40 °C 82 2:1 55:45 3 I-50 NBS PhMe:CHCl3 (2:1) -40 °C 70 1.2:1 50:50 4 I-51 NBS PhMe:CHCl3 (2:1) -40 °C 88 1.5:1 69:31 [a] drs were estimated by 1H NMR (500 MHz) analysis. [b] ers were almost the same for two diastereomers. N N N O N H O O HO N O H H H H N N O O O O S O N N N N I-49 I-50 I-51 (DHQD)2PHAL (DHQD) A structural advantage of this catalyst is that there are many potential points of optimization that could lead to an increase in the enantioselectivity of the reaction. The general structure I-52 highlights the domains for further studies. We could investigate steric and electronic perturbations, as well as the nature of the carbonyl linker between the aryl group and the alkaloid (carbamate/thiocarbamate, urea/thiourea). The influence of different substitutions on the quinoline ring could be probed, as well as modulation of the basicity of the quiniclidine nitrogen atom. 18 R5 N –or– N R H R4 N Y H –or– H R3 R1 X R6 R = Alk, Bn X R2 –or– N I-52 X/Y = O/N, S/O, O/O, S/N X R1-6 = H, X, OR, Alk, CF3 Figure I-17. Generalized structures for basic catalysts based on the cinchona alkaloid structure Before optimizing the catalyst structure, we intended to study different conditions that may affect the enantiomeric ratio. As shown in Table I-3, we altered temperature (Table I-3, entry 2), solvent and bromine source, however, none of them improved the er to more than 69:31%. Table I-3. Reaction optimization for cat. I-51; temperature, solvent and Br source were altered O Br (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O Solvent (0.03 M) I-45 O Temp.; 20 h I-46a O I-46b Entry Cat. Br Source Solvent Temp. era (%) 1 I-51 NBS PhMe:CHCl3 (2:1) 0 °C 66:34 2 I-51 NBS PhMe:CHCl3 (2:1) -40 °C 69:31 3 I-51 NBS PhMe -40 °C 52.5:47.5 19 Table I-3 (cont’d) 4 I-51 NBS PhMe:CHCl3 (2:1) -50 °C 65:35 5 I-51 NBS CHCl3 -40 °C 60:40 6 I-51 DBDMH PhMe:CHCl3 (2:1) -40 °C 66.5:33.5 7 I-51 NBP PhMe:CHCl3 (2:1) -40 °C 66.5:33.5 Isolated yields are between 68-93%; drs were estimated by 1H NMR (500 MHz) analysis and were between (1.5:1 to 2:1); NBP is N-bromophthalimide. [a] ers were almost the same for two diastereomers. The data demonstrated that -40 °C, NBS as bromine source, and a 2:1 mixture of PhMe:CHCl3 gave the optimal enantiomeric outcome. Based on these initial results, we realized the need to alter the catalyst structure to further increase enantioselectivity. Our general strategy for synthesizing the catalysts are summarized in Figure I-18. Proper cinchona alkaloid derivatives was synthesized and reacted with functionalized isocyanate or isothiocyanate. 20 N HO 1. MsCl, NEt3 1. BBr3 H PhCH2Br Ph3P, DIAD, DPPA 2. tartaric acid, H2O 2. i-PrBr, Cs2CO3 3. Ph3P, DIAD, DPPA (overall 51%) 71% O 61% (overall 21%) N Cl N N Ph N N HO HO H 2N H 2N H H H H Oi-Pr O O O N N N N R5 N –or– N R R5 (CCl3)2CO R5 H R4 NH2 Et3N R4 N R4 N Y H C NaH H or X R = Bn R1 X R6 R3 R1 CS2, K2CO3 R3 R1 R3 R2 TCT, NaOH R2 R2 N X= O, S X/Y = O/N, S/N, O/O, S/O R1-6 = H, X, OR, Alk, CF3 Figure I-18. General synthesis of basic catalysts Our first attempt was focused on the carbonyl linker between the aryl group and the alkaloid. In addition, we synthesized the carbamate, urea, and thiourea version of thiocarbamate catalyst I-51. As illustrated in Table I-4, running the reaction in the presence of urea catalyst I-52 and thiourea catalyst I-53 dropped the enantiomeric ratio to 55:45% and 50:50%, respectively while carbamate catalyst I-54 increased it drastically to 85:15%. 21 Table I-4. Study of the effects of different carbonyl linkers on asymmetric bromospirolatonization O Br (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O Solvent (0.03 M) I-45 O Temp.; 20 h I-46a O I-46b Entry Cat. Br Source Solvent Temp. dra (a:b) erb (%) 1 I-51 NBS PhMe:CHCl3 (2:1) -40 °C 1.5:1 69:31 2 I-52 NBS PhMe:CHCl3 (2:1) -40 °C 1.1:1 55:45 3 I-53 NBS PhMe:CHCl3 (2:1) -40 °C 1:1.1 50:50 4 I-54 NBS PhMe:CHCl3 (2:1) -40 °C 1.7:1 85:15 Isolated yields were between 72-94%. [a] drs were estimated by 1H NMR (500 MHz) analysis. [b] ers were almost the same for two diastereomers. O H H N O H H N O H N N N N N N O H H H O O O O S O O O O N N N I-52 I-53 I-54 Catalyst I-54 has the potential to be an ideal candidate for asymmetric bromospirolactonization; and as such, we sought to understand the different conditions that may influence the enantiomeric ratio. As shown in Table I-5, we altered temperature, solvent, and bromine source. Also, we studied the effect of different additives such as benzoic acid and 4-nitrobenzenesulfonamide (NsNH2). 22 Table I-5. Reaction optimization for cat. I-54; temperature, solvent and Br source were altered O Br (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O Solvent (0.03 M) I-45 O Temp.; 20 h I-46a O I-46b Entry Cat. Br Source Solvent Temp. Time (h) era (%) 1 I-54 NBS PhMe:CHCl3 (2:1) 0 °C 12 68:32 2 I-54 NBS PhMe:CHCl3 (2:1) -20 °C 20 74.5:25.5 3 I-54 NBS PhMe:CHCl3 (2:1) -30 °C 20 80:20 4 I-54 NBS PhMe:CHCl3 (2:1) -40 °C 20 85:15 5 I-54 NBS PhMe:CHCl3 (2:1) -50 °C 24 73:27 6d I-54 NBS PhMe:CHCl3 (2:1) -40 °C 20 73:27 7 I-54 NBS PhMe:CHCl3 (2:1) - 70 °C 28 61.5:38.5 8 I-54 NBS PhMe:CHCl3 (1:1) - 40 °C 20 82:18 9 I-54 NBS PhCl - 40 °C 20 73.5:26.5 10 I-54 NBS ACN - 40 °C 20 56:44 11 I-54 NBS Toluene - 40 °C 20 62.5:37.5 12 I-54 NBS CHCl3 - 40 °C 16 80:20 13e I-54 NBS PhMe:CHCl3 (2:1) -40 °C 20 78:22 14f I-54 NBS PhMe:CHCl3 (2:1) -40 °C 20 77:23 15 I-54 DBDMH PhMe:CHCl3 (2:1) -40 °C 20 65.5:35.5 23 Table I-5 (cont’d) 16 I-54 NBA PhMe:CHCl3 (2:1) -40 °C 20 76:24 17 I-54 NBP PhMe:CHCl3 (2:1) -40 °C 20 73:27 [a] ers were almost the same for two diastereomers. [b] drs were estimated by 1H NMR (500 MHz) analysis and were between 1.1:1 to 2:1[c] Isolated yields were between 66-94%. [d] Chloroform included 0.75% EtOH [e] Benzoic acid (1 equiv) was added as an additive. [f] NsNH2 (1 equiv) was added as an additive.[g] NBA is N-bromoacetamide. Between several evaluated bromine sources, NBS gave the best results, with an optimal temperature of -40°C. Higher temperatures reduced the er due to increasing rate of the background reactions. Lower temperature led to a decrease in er as well, which may suggest that the catalyst conformation is altered or catalyst is aggregated. Nonetheless, the 2:1 mixture of solvents (PhMe:CHCl3) was optimal. At this point, we focused on the electronic and steric effects of the carbamate aryl group. First, we investigated the impact of electron-withdrawing groups (EWG) such as CF3 on the phenyl ring (catalysts I-55 and I-56, Table I-6), however these catalysts resulted in significantly lower enantiomeric ratio compared to the electron-rich dimethoxy aryl catalyst I-54. Based on this observation, we kept the methoxy group at the ortho position and introduced a methyl group at the meta position, which based on Hammett values, is slightly electron- donating (catalysts I-57 and I-58, Table I-6). We also varied the meta-methyl group with methoxy, which is a weak EDG at this position (catalyst I-59). The other catalyst was made from 2-methyl-4-methoxy isocyanate: the methoxy and methyl at these positions act as a strong and weak EDG, respectively (catalyst I-60). 24 Table I-6. Catalyst optimization; study of electronic effect on the carbamate aryl group O Br (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O Solvent (0.03 M) I-45 O Temp.; 20 h I-46a O I-46b Entry Cat. Br Source Solvent Temp. dra (a:b) erb (%) 1 I-55 NBS PhMe:CHCl3 (2:1) -40 °C 1.7:1 62.5:37.5 2 I-56 NBS PhMe:CHCl3 (2:1) -40 °C 1.1:1 58:42 3 I-57 NBS PhMe:CHCl3 (2:1) -40 °C 1.8:1 64:36 4 I-58 NBS PhMe:CHCl3 (2:1) -40 °C 1:1.2 60:40 5c I-59 NBS PhMe:CHCl3 (2:1) -40 °C 1.1:1 52.5:47.5 6 I-60 NBS PhMe:CHCl3 (2:1) -40 °C 1.5:1 70:30 Isolated yields were between 72-94%. [a] drs were estimated by 1H NMR (500 MHz) analysis. [b] ers were almost the same for two diastereomers. [c] yield was less than 30%. H N H N O H N CF3 N O CF3 N O N O H H H O O S O O O CF3 CF3 N N N I-55 I-56 I-57 O H N O H N H N N O N O N O H H H S O O O O O O O N N N I-58 I-59 I-60 All these changes decreased the enantiomeric ratio compared to the 2,4- dimethoxy catalyst I-54. As tabulated in Table I-7, we then investigated trimethoxy- 25 substituted synthesized ([2,3,4-],[2,4,6-] and [3,4,5-] trimethoxy catalysts) catalyst I-61, I- 62 and I-63 respectively. The steric effect of functional groups was examined by means of introduction of bulky isopropyl relative to the methyl group, generating the 2,4- diisopropyl derivative (catalyst I-64). The influence of substitutions on the quinoline ring was additionally probed. To do this, we envisioned substituting the methoxy group with hydrogen to see if an EDG is obligatory for a functional catalyst (catalyst I-65). Previously, the steric effect of this functional group on the quinoline showed a large impact on the enantiomeric ratio for other reactions.25 As such, we switched the methyl group with a bulky isobutyl to test the steric effect. Table I-7. Catalyst optimization; electronic and steric effect on aryl carbamate and quinoline O Br (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O Solvent (0.03 M) I-45 O Temp.; 20 h I-46a O I-46b Entry Cat. Br Source Solvent Temp. dra (a:b) erb (%) 1c I-61 NBS PhMe:CHCl3 (2:1) -40 °C 2.2:1 52.5:47.5 2c I-62 NBS PhMe:CHCl3 (2:1) -40 °C 1.2:1 62:38 3c I-63 NBS PhMe:CHCl3 (2:1) -40 °C 1.6:1 56.5:43.5 4 I-64 NBS PhMe:CHCl3 (2:1) -40 °C 2:1 80.5:19.5 5 I-65 NBS PhMe:CHCl3 (2:1) -40 °C 2:1 79:21 6 I-66 NBS PhMe:CHCl3 (2:1) -40 °C 1.8:1 77.5:22.5 Isolated yields were between 63-84%. [a] drs were estimated by 1H NMR (500 MHz) analysis. [b] ers were almost the same for two diastereomers. [c] yield was less than 30%. 26 Table I-7 (cont’d) O H N O H N H N O N O N O O N O H H H O O O O O O O O O O O N N N I-61 I-62 I-63 O N O H N O H N H N O N O N O H H H O O O O O H O O O N N N I-64 I-65 I-66 The trimethoxy substituted catalysts I-61, I-62 and I-63 did not lead to enantiomeric ratios higher than the 2,4-dimethoxy substituted catalyst I-54. The data showed that the sterics of the alkoxy group do not have an effect on enantiomeric excess of the reaction. Studies conducted on the quinoline moiety revealed that the functional group at C6 position does play a critical role in the enantiomeric excess of the reaction. Also, replacing the methoxy with hydrogen decreased the er. However, the sterics of that functional group did not affect the reaction to any appreciable extent. In the next step, the pseudo-enantiomer of catalyst I-54 was synthesized (catalyst I-67) and was examined in the enantioselective bromospirolactonization reaction, which led to opposite enantioinduction with a slightly lower er (Table I-8). Subsequently, we studied the amide derivative of cinchona alkaloid (catalyst I-68) which was utilized in prior asymmetric halofunctionalizations. Also, we tested catalyst I-67 which was recently reported for the domino halocyclization reaction14 (Table I-8, entry 3) The urea and carbamate derivative of this catalyst was also synthesized (I-68 and I-69) and examined 27 for asymmetric bromospirolactonization. These series of catalysts showed moderate to good yield (58-89%) and up to 1.5:1 dr but, none of these catalysts was able to improve the er compared to catalyst I-54. Table I-8. Study of thiourea, urea and carbamate catalysts O Br (1.2 equiv) Br Cat. (15 mol%) Ph O Br OH Ph O O Ph O + O Solvent (0.03 M) I-45 O Temp.; 20 h I-46a O I-46b Entry Cat. Br Source Solvent Temp. dra (a:b) erb (%) 1 I-67 NBS PhMe:CHCl3 (2:1) -40 °C 1.5:1 75:25 2 I-68 NBS PhMe:CHCl3 (2:1) -40 °C 1:1 52.5:47.5 3 I-69 NBS PhMe:CHCl3 (2:1) -40 °C 1.1:1 57:43 4 I-70 NBS PhMe:CHCl3 (2:1) -40 °C 1.1:1 52:48 5 I-71 NBS PhMe:CHCl3 (2:1) -40 °C 1:1 50:50 Isolated yields were between 58-89%. [a] drs were estimated by 1H NMR (500 MHz) analysis. [b] ers were almost the same for two diastereomers. O O N N H H N O N H H O O O O O O N N I-67 I-68 O O O S O O N N N N O N H H H H H N O N O N O I-69 I-70 I-71 28 The upshot of these studies is that catalyst I-54 remached the best of the group. While we were actively seeking to optimize this catalyst and other parameters of the reaction condition to improve the enantiomeric ratio, we aimed to examine the generality of this method. In order to do this, we sought to synthesize a library of appropriate substrates. As shown in Figure I-19 (method A), Our first method for generating the phenyl substrate I-45 proceeded by generating the phosphonium ylide I-73 from 3- bromopropanol, which underwent a Wittig reaction with benzaldehyde to generate homoallylic alcohol I-74. After bromination of alcohol in the presence of PBr3, we attempted to react with succinic anhydride via its corresponding Grignard. This method has two major drawbacks for making the substrate library; the first being that the final step is low yielding, and the yield tended to fluctuate. Secondly, the overall lack of atom and stepwise economy meant a laborious process to complete all 4 steps for each substrate. To mitigate this issue, we designed and develop a divergent method to make the starting materials. As shown in Figure I-19 (method B), compound I-80 was synthesized following the reported procedure.26 The allyl bromide reacted with methyl acetoacetate in a basic condition to generate the keto ester I-77, which was converted to di-ester I-79 in the presence of sodium hydride. Decarboxylation with potassium hydroxide led to the formation of a keto ester substrate with a terminal alkene I-80 (we run large scale reactions for these 3 steps). Lastly, every substrate was stitched together with the terminal olefin, via a Grubbs cross metathesis reaction. The substrates that were successfully synthesized are listed in Table I-9. 29 Method A: PPh3 (1.2 equiv) Benzaldehyde (0.8 equiv) Br OH Br Ph3P OH Toluene LiHMDS (2.5 equiv) I-72 reflux, 96% I-73 THF, -20 ºC to r.t., 74% 1) Mg turning (4 equiv.) PBr3 (0.33 equiv.) I2 (cat.), THF, 40 ºC OH Br Ph Ph Et2O 2) Succinic anhydride (0.5 equiv.) I-74 0 ºC to r.t., 48% I-75 CuI (7.5 mol%) THF, -20 ºC to r.t., 43% O OH Ph I-45 O Method B: Br (1.2 equiv) I-78 (1 equiv) O O NaH (1.5 equiv) O O NaH (1.5 equiv) O n-BuLi (1.1 equiv) O THF, 0 ºC to r.t. THF, 0 ºC, 100% I-77 65% I-76 O O O KOH (5 equiv) R (3 equiv) O OH O EtOH, reflux, 61% Grubbs-II (15 mol%) I-80 O DCM, reflux I-79 O O O OH Br R O I-81 O I-78 Figure I-19. Synthetic methods for making substrates 30 Table I-9. Grubbs cross metathesis results O O R (3 equiv) OH OH Grubbs-II (15 mol%) R I-80 O DCM, reflux I-81 O Entry R Product Yield (%) Entry R Product Yield (%) 1 Ph I-45 71 7 4-CH3CO2-C6H4 I-87 57 2 4-CH3O-C6H4 I-82 61 8 b-naphthyl I-88 61 3 3-NO3-C6H4 I-83 33 9 4-CH3CO-C6H4 I-89 49 4 4-CF3-C6H4 I-84 42 10 t-Bu I-90 54 5 4-CH3-C6H4 I-85 72 11 Cy I-91 38 6 4-F-C6H4 I-86 55 12 C4 H4 S I-92 59 As summarized in Table I-10, the generality of the uncatalyzed bromospirolactonization reaction was investigated. The keto-acids presented in Table I- 10 were subjected to halenium atom initiated cascade spirolactonization under optimized conditions. The crystal structure of product I-45 was used to establish the relative stereochemistry in the halogenated spirolactone products. The reactions proceeded in moderate to high yield for different functional groups and different ring sizes. The rate was slower for the 4-chloro phenyl substrate and led to lower yield (Table I-10, entry 5) compared to phenyl substrate (Table I-10, entry 1). One hypothesis is that the electron withdrawing effect of chlorine at the para position decreases the nucleophilicity of the double bond toward abstracting the halogen. As shown in Table I-10 (entry 8), the [6,6]- 31 Table I-10. Substrate scope study of uncatalyzed bromospirolactonizations R3 R2 O Br Br NBS (1.1 equiv.) R1 O n OH R1 n Ph O O O PhMe, R2 O R3 O 1 to 24 h, rt. product of entry 7 O Entry R1 R2 R3 n Product Yield (%) dra 1 Ph H H 1 I-45 92 2.5:1 2 4-CH3O-C6H4 H H 1 I-93 89 1:1.2 3 4-CH3-C6H4 H H 1 I-94 90 1:1.5 4 4-F-C6H4 H H 1 I-95 81 1:1.85 5 4-Cl-C6H4 H H 1 I-96 40 1:1.1 6 C4 H4 S H H 1 I-97 58 1:1 7 H H Ph 1 I-98 84 1:1 8 Ph H H 2 I-99 79 10:1 [a] drs were estimated by 1H NMR (500 MHz) analysis. spirolactone core was obtained via diastereoselective bromospirolactonization (10:1 dr). The crystal structure of the major diastereomer of I-99 product was obtained and showed the carboxylic acid reside in the axial position as anticipated due to anomeric stabilization (Figure I-20). The corresponding [5,5]-spirolactone I-98 was formed in good yield by installing the phenyl group at the R3 position (Table I-10, entry 7). The transition state of [5,5]-spirolactonization does not enjoy the same level of stability from the anomeric effect, thus leading to reduced dr. 32 Br Ph O O I-99a O Figure I-20. X-ray crystal structure of I-99a The generality of the asymmetric catalytic bromospirolactonization is reported in Table I-11. The enantioselective reaction of the above keto-acid substrates were exploited with catalyst I-54 under optimized condition. The reactions proceeded in moderate to excellent yield for different functional groups and ring sizes. The distereoselectivity ranged from 1:1 to 1.9:1 and did not vary significantly between substrates. Modulating the electronic profile or the size of the substituents, had a significant effect on the enantiomeric ratio of the reactions. In case of electron rich 4- methoxy substrate (Table I-11, entry 2), the enantiomeric ratio dropped drastically to 57.5:42.5% relative to the phenyl substituted 85:15% (entry 1). Presumably, strong electron donating group at para position would increase the nucleophilicity of the olefin and not requiring the activation for bromenium capture. In this system, the oxacarbenium template dominated by NAAA would be absent. The enantiomeric ratio of the 4-fluoro- phenyl substrate was the same as for phenyl, since fluoro is slightly electron withdrawing at para position (entry 4) and, 4-chloro and 4-methyl reactions resulted in a slightly lower er (entry 3 and 4). This reaction was not compatible with different ring sizes and as shown in Table I-11, the er dropped dramatically for [5,5] and [6,6] substrates (entries 6 and 7). 33 Table I-11. Substrate scope study of catalytic asymmetric bromospirolactonizations R3 R2 O NBS (1.2 equiv.) Br Br Cat. (15 mol%) R1 O n OH R1 n Ph O O O PhMe:CHCl3 (2:1) R2 O R3 O 20 to 48 h, -40 ºC product of entry 6 O Entry R1 R2 R3 n Product Yield (%) dra erb 1 Ph H H 1 I-45 94 1.7:1 85:15 2 4-CH3O-C6H4 H H 1 I-93 58 1.5:1 57.5:42.5 3 4-CH3-C6H4 H H 1 I-94 89 1.9:1 76:24 4 4-F-C6H4 H H 1 I-95 78 1.7:1 84:16 5 4-Cl-C6H4 H H 1 I-96 69 1.7:1 75:25 6 H H Ph 1 I-98 81 1:1 60:40 7 Ph H H 2 I-99 83 1.5:1 57.5:42.5 a] drs were estimated by 1H NMR (500 MHz) analysis. [b] ers were almost the same for two diastereomers. I-5 Future work I-5-1 Development of di-bromospirolactonization During reaction optimization studies on mono-bromospirolactonization, we found that an excess amount of a more reactive bromine source (toward halofunctionalization) led to a second bromination of the oxane ring. As shown in Figure I-21a, excess of 3-bromo- 1-chloro-5,5-dimethylhydantoin (BCDMH); generated in situ by combining equimolar amounts of DBDMH and DCDMH was able to furnish the di-bromospirolactonization product. The relative stereochemistry of di-brominated spirolactone product was confirmed by an X-ray crystal structure. This reaction is currently under further 34 development and optimization. Also, in the case that a second bromine is substituted after generation of the mono-bromospirolactone, there is a great potential to develop di- halogenated spirolactones with different halogens (Figure I-21b). Lastly, we could study the first enantioselective di-bromospirolactone using the carbamate derivatives of cinchona alkaloid catalyst I-54. a. di-bromospirolactonization result and X-ray crystal structure DCDMH, DBDMH O (1.5 equiv each) Ph Br O O Br OH Ph O PhMe, 3 h, rt. O 28%, >99 dr I-45 I-100 b. proposed di-halospirolactonization O Br Br OH NBS Ph O O X Ph O OX Ph O O O I-45 I-46 I-101 Figure I-21. Development of di-bromo and di-halospirolactonization I-5-2 Toward the total synthesis of Obtusallenes V and VI After developing the mono and di-bromospirolactonization reaction, we intended to extend our chemistry by applying this method to access Obtusallene VI, a dihalogenated C15-macrocyclic ether. This macrocycle was isolated in 2000 from a red seaweed, Laurencia obtuse.27, 28 Since its isolation, its synthesis has not been reported and remains an elusive synthetic target. The synthesis of obtusallene VI will be pursued by first making 35 keto-acid I-80 as described above, which will undergo a cross metathesis29 with the known protected alcohol I-10230 to afford I-103. This intermediate is then set up for the key bromo spirolactonization reaction to generate compound I-104 (Figure I-22). As shown in Table I-11, we demonstrated the synthesis of the 5,5-spirolactone and the transformation of I-103 to I-104 would be carried out under the same conditions. Currently, this step is under investigative screening with different catalysts. We propose the use of the Comins reagent which was used to make the vinyl triflate of a similar compound previously31 followed by a Negishi cross-coupling with the Reformatsky derived zincated ethyl ester should presumably lead to I-105.32-34 The conjugated ester I- 106 would be generated via b-chlorination of the vinyl ether in the presence of a mild chlorenium source and subsequent deprotonation.35-37 The olefin I-106 should be reduced by hydrogen atom transfer methods due to the susceptibility of the alkyl bromide and allylic chloride to reduction.38-40 Putatively, the reduction will occur syn to the chlorine, since in an energy minimized structure of I-106, the alternate face is sterically hindered. This is presumed to be mediated by interactions with the spiro oxygen atom. Reducing the ethyl ester to the aldehyde and subsequent Julia-Kocienski olefination results in enyne I-110,41 which, after deprotection of the alcohol will undergo an intramolecular bromoetherification,42 generating natural product I-111. It should however be noted that although the stereochemistry of the C4 ether bond originates from the olefin face- selectivity (calculation showed DE >2.2 kcal/mol for the Z-110 rotomer that leads to the undesired face selectivity), the stereochemistry for the allenyl bromide is unpredictable. 36 Alternatively, the E-olefin of I-110 can be synthesized with I-109,41 and tested for the bromoetherification that leads to obtusallene VI. OTBS O OTBS O Brønsted or I-102 Lewis basic catalyst OH HG-II OH NBS I-80 O I-103 O (1 equiv) H 1. Comins reagent H Br O O Br O O CO2Et NCS O 2. BrZn CO2Et MeCN Me OTBS Me OTBS Pd0 I-104 I-105 H2 Cl Cl H H Br O O diimide Br O O coordination to reduction CO2Et oxygen can bulk CO2Et Me OTBS Me OTBS the bottom face I-106 I-107 DFT-Miminized structure of I-106 Cl 7 Cl 1. DIBAL, –78 ºC H 2. J-K olefination, I-108 H Br O Br O O 4 O C C 1 3. TBAF O H OH H 13 Me Br Z-I-110 Br Me I-111 obtusallene VI Cl O O TMS S S Ph3P E-olefin Tf N N of I-110 N I-108, with I-109, with Tf NaHMDS n-BuLi Comins reagent Figure I-22. Proposed total synthesis of obtusallenes VI 37 In summary, we have developed a bromospirolactonization method based on the application of halenium affinity (HalA) as a guiding tool in conjunction with Nucleophile Assisted Alkene Activation (NAAA). A series of acid/base catalysts were studied to develop a catalytic asymmetric bromospirolactonization reaction, and ultimately led to the conlcusion that carbamate and thiocarbamate derivatives of cinchona alkaloid-based catalysts are able to induce chirality in the reaction. Further optimization revealed that a 2,4-methoxy functionalized carbamate would lead to the highest enantiomeric ratio. While further catalyst optimization is ongoing in our lab, we have tested and demonstrated the generality of the reaction. 38 I-6 Experimental section I-6-1 General remarks: Molecular sieves (4Å) were dried at 160 °C under 0.25 mtorr vacuum prior to use. Unless otherwise mentioned, solvents were purified as follows. CHCl3 (amylene stabilized) was purchased from Sigma Aldrich and incubated over 4 Å MS for 48 h prior to use. Toluene and CH2Cl2 were dried over CaH2 whereas THF and Et2O were dried over sodium (dryness was monitored by colorization of benzophenone ketyl radical); they were freshly distilled prior to use. NMR spectra were obtained using a 500 MHz or 600 MHz Varian NMR spectrometer and referenced using the residual 1H peak from the deuterated solvent. Waters 2795 (Alliance HT) instrument was used for HRMS (ESI) analysis with polyethylene glycol (PEG-400-600) as a reference. Column chromatography was performed using Silicycle 60 Å, 35-75 µm silica gel. Pre-coated 0.25 mm thick silica gel 60 F254 plates were used for analytical TLC and visualized using UV light, iodine, potassium permanganate stain, p-anisaldehyde stain or phosphomolybdic acid in EtOH stain. Halofunctionalization reactions were performed in the absence of light. N- bromosuccinimide (NBS), N-chlorosuccinimide (NCS), 1,3-dichloro-5,5- dimethylhydantoin (DCDMH), and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) were re- crystallized prior to use. All other commercially available reagents and solvents were used as received unless otherwise mentioned. 39 I-6-2 General procedure for racemic bromo spirolactonization of keto-acids R3 R2 O Br n Br (1.1 equiv.) R1 O m OH R1 n m Solvent (0.03 M) R2 O R3 O Temp.; time O The keto-acid substrate (0.1 mmol) and N-bromosuccinimide, NBS (0.11 mmol) were suspended in dry toluene (3 mL) in a 25 mL round bottom with a magnetic stir bar under a nitrogen balloon. The reaction mixture was stirred at room temperature and followed by TLC. Upon completion, the reaction mixture was diluted with hexanes (3 mL) and quenched by addition of sodium thiosulfate (3 ml of a 10% aqueous solution). The organic layer was separated, and the aqueous layer was extracted with hexanes (3 x 3 mL). The combined organic layers were dried with anhydrous Na2SO4 and concentrated under reduced pressure at room temperature to give the crude product. Crude 1H NMR was used to determine the diastereoselectivity of the reaction. The crude product was then purified by column chromatography (silica, ethyl acetate/hexanes = 1:10 ) leading to the pure bromo spirolactone products. I-6-3 General procedure for catalytic asymmetric bromo spirolactonization of keto- acids R3 Br (1.2 equiv.) R2 O Br n Cat. (15 mol%) R1 O OH m R1 n m Solvent (0.03 M) R2 O R3 O Temp.; time O The N-bromosuccinimide, NBS (0.12 mmol) and catalyst (15 mol %) placed in a test tube with a magnetic stir bar and capped with a rubber septum under an argon balloon 40 in the dark (the reaction covered with aluminum foil). The reaction tube cooled to – 40 °C and a mixture of dry toluene (2 mL) and dry chloroform (1 mL) was added via syringe. After 20 minutes, the keto-acid substrate (0.1 mmol) was added in one portion. The reaction stirred at this temperature and followed by TLC. Upon completion, the reaction mixture was diluted with hexanes (3 mL) and quenched by addition of sodium thiosulfate (3 ml of a 10% aqueous solution). The organic layer was separated, and the aqueous layer was extracted with hexanes (3 x 3 mL). The combined organic layers were dried with anhydrous Na2SO4 and concentrated under reduced pressure at room temperature to give the crude product. Crude 1H NMR was used to determine the diastereoselectivity of the reaction. The crude product was then purified by column chromatography (silica, ethyl acetate/hexanes 10%) leading to the pure bromo spirolactone products. I-6-3-1 Analytical data Br Ph O O I-46a O The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1.7:1) and isolated as a white solid (29 mg, 94% yield, 85:15 er). 1H NMR (500 MHz, Chloroform-d) δ 7.39 – 7.34 (m, 5H), 4.92 (d, J = 10.5 Hz, 1H), 4.03 (ddd, J = 11.9, 10.5, 4.6 Hz, 1H), 2.75 (dt, J = 17.8, 10.6, Hz, 1H), 2.62 – 2.45 (m, 3H), 2.33 – 2.27 (m, 1H), 2.16 – 2.04 (m, 3H). 41 13C NMR (126 MHz, Chloroform-d) δ 175.96, 138.27, 128.86, 128.28, 127.85, 107.06, 79.25, 49.88, 41.75, 35.68, 33.95, 31.72, 27.93. HPLC analysis: Chiralpak IA, 99:1 hexane/i-PrOH, flow rate = 1 mL/min, λ = 215 nm, retention time = 22.3 min (major), 26.2 min (minor). HRMS: TOF MS AP+ (C14H16BrO3): Calc. [M + H]+: 311.0285, Found [M + H]+: 311.0287. Br Ph O O O I-46b 1H NMR (500 MHz, Chloroform-d) δ 7.47 – 7.33 (m, 5H), 4.68 (d, J = 9.8 Hz, 1H), 4.10 (td, J = 10.2, 4.6 Hz, 1H), 2.79 – 2.48 (m, 4H), 2.38 – 2.07 (m, 4H). 13C NMR (126 MHz, Chloroform-d) δ 175.09, 138.00, 128.94, 128.37, 127.67, 107.33, 81.68, 49.70, 34.73, 31.49, 29.60, 27.70. HRMS: TOF MS AP+ (C14H16BrO3): Calc. [M + H]+: 311.0285, Found [M + H]+: 311.0287. Br 4-OCH3-C6H4 O O I-93a O The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1.5:1) and isolated as a white solid (20 mg, 58% yield, 57.5:42.5 er). 42 1H NMR (500 MHz, Chloroform-d) δ 7.31 (d, J = 8.2 Hz, 2H), 6.92 (d, J = 8.1 Hz, 2H), 4.91 (d, J = 10.6 Hz, 1H), 4.05 (td, J = 10.6, 4.7 Hz, 1H), 3.83 (s, 3H), 2.83 – 2.72 (m, 1H) 2.64 – 2.46 (m, 3H), 2.31 (t, J = 11.5 Hz, 1H), 2.19 – 2.06 (m, 3H). 13C NMR (126 MHz, Chloroform-d) δ 175.96, 159.88, 130.55, 129.01, 113.68, 107.12, 78.86, 55.27, 50.19, 35.71, 33.96, 31.77, 27.94. HPLC analysis: Chiralpak IA, 98:2 hexane/i-PrOH, flow rate = 1 mL/min, λ = 215 nm, retention time = 31.5 min (major), 39.3 min (minor). HRMS: TOF MS AP+ (C15H18BrO4): Calc. [M + H]+: 341.0390, Found [M + H]+: 341.0392. Br 4-OCH3-C6H4 O O O I-93b 1H NMR (500 MHz, Chloroform-d) δ 7.35 (d, J = 8.53 Hz, 2H), 6.92 (d, J = 8.82 Hz, 2H), 4.64 (d, J = 9.9 Hz, 1H), 4.09 (td, J = 10.2, 4.6 Hz, 1H), 3.83 (s, 3H), 2.80 – 2.51 (m, 4H), 2.34 – 2.05 (m, 4H). 13C NMR (126 MHz, CDCl3) δ 175.08, 159.95, 130.28, 128.87, 113.75, 107.36, 81.33, 55.29, 50.10, 34.82, 31.55, 29.59, 27.72. HRMS: TOF MS AP+ (C15H18BrO4): Calc. [M + H]+: 341.0390, Found [M + H]+: 341.0390. Br 4-CH3-C6H4 O O O I-94a 43 The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1.9:1) and isolated as a white solid (29 mg, 89% yield, 76:24 er). 1H NMR (500 MHz, Chloroform-d) δ 7.29 – 7.26 (m, 2H), 7.19 (d, J = 7.9 Hz, 2H), 4.90 (d, J = 10.5 Hz, 1H), 4.06 (ddd, J = 12.0, 10.5, 4.7 Hz, 1H), 2.76 (ddd, J = 17.9, 10.7, 9.6 Hz, 1H), 2.62 – 2.45 (m, 3H), 2.37 (s, 3H), 2.30 (ddd, J = 13.3, 9.5, 2.2 Hz, 1H), 2.16 – 2.06 (m, 3H). 13C NMR (126 MHz, Chloroform-d) δ 176.02, 138.74, 135.36, 129.03, 127.73, 107.10, 79.07, 49.95, 35.68, 33.95, 31.74, 27.93, 21.29. HPLC analysis: Chiralpak IA, 98:2 hexane/i-PrOH, flow rate = 1 mL/min, λ = 215 nm, retention time = 14.4 min (major), 18.2 min (minor). HRMS: TOF MS AP+ (C15H18BrO3): Calc. [M + H]+: 325.0441, Found [M + H]+: 325.0439. Br 4-CH3-C6H4 O O O I-94b 1H NMR (600 MHz, Chloroform-d) δ 7.32 (d, J = 7.9 Hz, 2H), 7.20 (d, J = 7.9 Hz, 2H), 4.65 (d, J = 9.8 Hz, 1H), 4.11 (ddd, J = 10.7, 9.8, 4.6 Hz, 1H), 2.78 – 2.66 (m, 2H), 2.65 – 2.59 (m, 1H), 2.65 – 2.60 (m, 1H), 2.38 (s, 3H), 2.32 – 2.21 (m, 2H), 2.15 – 2.07 (m, 2H). 44 13C NMR (151 MHz, Chloroform-d) δ 175.09, 138.82, 135.10, 129.09, 127.56, 107.33, 81.56, 49.83, 34.76, 31.52, 29.62, 27.71, 21.25. Br 4-F-C6H4 O O O I-95a The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1.7:1) and isolated as a white solid (25 mg, 78% yield, 84:16 er). 1H NMR (500 MHz, Chloroform-d) δ 7.43 – 7.36 (m, 2H), 7.06 (t, J = 8.7 Hz, 2H), 4.65 (d, J = 9.9 Hz, 1H), 4.02 (td, J = 10.6, 4.5 Hz, 1H), 2.79 – 2.50 (m, 4H), 2.34 – 2.05 (m, 4H). 13C NMR (126 MHz, Chloroform-d) δ 175.01, 162.89 (d, J = 247.6 Hz), 133.94 (d, J = 3.5 Hz), 129.43 (d, J = 8.7 Hz), 115.33 (d, J = 21.6 Hz), 107.32, 81.00, 49.83, 34.78, 31.47, 29.55, 27.67. 19F NMR (470 MHz, Chloroform-d) δ -112.82 – -112.90 (m). HPLC analysis: Chiralpak IA, 98:2 hexane/i-PrOH, flow rate = 1 mL/min, λ = 215 nm, retention time = 21.6 min (major), 24.0 min (minor). HRMS: TOF MS AP+ (C14H15BrFO3): Calc. [M + H]+: 329.0190, Found [M + H]+: 329.0194. Br 4-F-C6H4 O O O I-95b 45 1H NMR (500 MHz, Chloroform-d) δ 7.40 – 7.34 (m, 2H), 7.07 (t, J = 8.4 Hz, 2H), 4.94 (d, J = 10.5 Hz, 1H), 3.99 (td, J = 11.3, 4.5 Hz, 1H), 2.84 – 2.46 (m, 4H), 2.38 – 2.02 (m, 4H), 13C NMR (201 MHz, Chloroform-d) δ 175.89, 162.84 (d, J = 248.08 Hz), 134.21, 129.56 (d, J = 8.3 Hz), 115.24 (d, J = 21.5 Hz), 107.03, 78.56, 50.02, 35.64, 33.93, 31.67, 27.90. 19F NMR (470 MHz, Chloroform-d) δ -112.68 – -112.76 (m, 1F). HRMS: TOF MS AP+ (C14H15BrFO3): Calc. [M + H]+: 329.0190, Found [M + H]+: 329.0191. Br 4-Cl-C6H4 O O O I-96a The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1.7:1) and isolated as a white solid (24 mg, 69% yield, 75:25 er). 1H NMR (500 MHz, Chloroform-d) δ 7.30 – 7.21 (m, 4H), 4.86 – 4.80 (d, J = 10.58, 1H), 3.89 (td, J = 11.6, 5.2 Hz, 1H), 2.71 – 2.61 (m, 1H), 2.53 – 2.37 (m, 3H), 2.22 (t, J = 11.9 Hz, 1H), 2.12 –1.97 (m, 3H). 13C NMR (126 MHz, Chloroform-d) δ 175.77, 136.81, 134.63, 129.21, 128.50, 106.94, 78.59, 49.70, 35.61, 33.92, 31.64, 27.85. HPLC analysis: Chiralpak IA, 98:2 hexane/i-PrOH, flow rate = 1 mL/min, λ = 215 nm, retention time = 14.3 min (major), 18.0 min (minor). 46 HRMS: TOF MS AP+ (C14H15BrClO3): Calc. [M + H]+: 344.9895, Found [M + H]+: 344.9895. Br 4-Cl-C6H4 O O O I-96b 1H NMR (500 MHz, Chloroform-d) δ 7.40 – 7.35 (m, 4H), 4.67 (d, J = 9.8, 1H), 4.04 (td, J = 10.0, 5.2 Hz, 1H), 2.80 – 2.52 (m, 4H), 2.36 – 2.07 (m, 4H). 13C NMR (126 MHz, Chloroform-d) δ 174.90, 136.56, 134.73, 129.04, 128.57, 107.27, 80.99, 49.50, 34.66, 31.39, 29.64, 27.64. HRMS: TOF MS AP+ (C14H15BrClO3): Calc. [M + H]+: 344.9895, Found [M + H]+: 344.9897. Br Ph O O O I-98a&b The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1:1) and isolated as a white solid (25 mg, 81% yield, 60:40 er). Diastereomer a: 1H NMR (500 MHz, Chloroform-d) δ 7.37 – 7.30 (m, 4H), 7.29 – 7.26 (m, 1H), 3.61 (d, J = 11.1 Hz, 1H), 3.55 (d, J = 11.1 Hz, 1H), 2.93 (dt, J = 17.6, 10.1 Hz, 1H), 2.71 – 2.28 (m, 7H). 47 13C NMR (126 MHz, Chloroform-d) δ 175.69, 143.80, 128.41, 127.77, 125.06, 116.76, 88.58, 42.56, 37.30, 35.32, 31.79, 29.07. HPLC analysis: Chiralpak IA, 98:2 hexane/i-PrOH, flow rate = 1 mL/min, λ = 215 nm, retention time = 17.7 min (major), 22.7 min (minor). HRMS: TOF MS AP+ (C15H18BrO3): Calc. [M + H]+: 311.0285, Found [M + H]+: 311.0285. Diastereomer b: 1H NMR (500 MHz, Chloroform-d) δ 7.41 – 7.35 (m, 4H), 7.34 – 7.29 (m, 1H), 3.77 (d, J = 10.7 Hz, 1H), 3.72 (d, J = 10.7 Hz, 1H), 2.93 (dt, J = 17.4, 9.6 Hz, 1H), 2.66 – 2.30 (m, 6H), 2.00 (td, J = 12.9, 8.0 Hz, 1H). 13C NMR (126 MHz, cdcl3) δ 175.47, 142.31, 128.29, 127.80, 125.39, 115.86, 88.68, 41.68, 36.39, 35.75, 31.71, 28.96. HRMS: TOF MS AP+ (C15H18BrO3): Calc. [M + H]+: 311.0285, Found [M + H]+: 311.0288. Br Ph O O I-99a O The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1.5:1) and isolated as a white solid (27 mg, 83% yield, 57.5:42.5 er). 48 1H NMR (500 MHz, Chloroform-d) δ 7.38 – 7.34 (m, 5H), 4.97 (d, J = 10.4 Hz, 1H), 3.99 (ddd, J = 12.2, 10.4, 4.4 Hz, 1H), 2.74 – 2.64 (m, 1H), 2.62 – 2.54 (m, 1H), 2.47 – 2.36 (m, 2H), 2.12 – 1.91 (m, 4H), 1.84 – 1.76 (m, 1H), 1.76 – 1.67 (m, 1H). 13C NMR (126 MHz, Chloroform-d) δ 170.77, 138.49, 128.68, 128.17, 127.88, 102.61, 78.08, 50.47, 36.78, 32.66, 30.26, 29.33, 15.26. HPLC analysis: Chiralpak AD-H, 98:2 hexane/i-PrOH, flow rate = 1 mL/min, λ = 215 nm, retention time = 15.2 min (minor), 17.3 min (major). HRMS: TOF MS AP+ (C15H19BrO3): Calc. [M - H]+: 323.0281, Found [M + H]+: 323.0280. Br C 4H 4S O O O I-97a The title compound was prepared according to the general procedure I-6-2 at 0.1 mmol scale. Product was formed as a mixture of diastereomers a and b (1:1) and isolated as a white solid (18 mg, 58% yield). 1H NMR (500 MHz, Chloroform-d) δ 7.24 (d, J = 5.0 Hz, 1H), 7.05 (d, J = 3.5 Hz, 1H), 6.92 (dd, J = 5.3, 4.0 Hz, 1H), 5.15 (d, J = 10.5 Hz, 1H), 3.96 (td, J = 11.2, 4.6 Hz, 1H), 2.79 – 2.64 (m, 1H), 2.53 – 2.37 (m, 3H), 2.29 – 2.20 (m, 1H), 2.11 – 1.91 (m, 3H). 13C NMR (126 MHz, Chloroform-d) δ 175.78, 141.36, 127.58, 126.41, 125.71, 106.95, 75.06, 50.54, 35.44, 33.85, 31.70, 27.88. 49 HRMS: TOF MS AP+ (C12H14BrO3S): Calc. [M + H]+: 316.9849, Found [M + H]+: 316.9847. Br C 4H 4S O O O I-97b 1H NMR (500 MHz, Chloroform-d) δ 7.32 (d, J = 5.5 Hz, 1H), 7.08 (d, J = 3.5 Hz, 1H), 7.02 – 6.95 (m, 1H), 5.08 (d, J = 8.0 Hz, 1H), 4.33 – 4.26 (m, 1H), 2.83 – 2.70 (m, 1H), 2.66 – 2.50 (m, 3H), 2.25 – 2.10 (m, 4H). 13C NMR (126 MHz, Chloroform-d) δ 175.04, 141.52, 126.40, 126.32, 126.01, 107.11, 49.66, 33.27, 30.90, 29.99, 27.79. Br Ph O O Br O I-100 The title compound was prepared according to the general procedure I-6-2 at 0.1 mmol scale, except using DCDMH, DBDMH (1 equiv. each) as bromine source. Product was formed as a single diastereomer and isolated as a white solid (11 mg, 28% yield). 1H NMR (500 MHz, Chloroform-d) δ 7.46 – 7.37 (m, 5H), 4.97 (d, J = 10.7 Hz, 1H), 4.50 (ddd, J = 11.9, 10.7, 4.3 Hz, 1H), 4.25 (t, J = 3.1 Hz, 1H), 3.12 – 3.03 (m, 1H), 2.88 – 2.71 (m, 2H), 2.59 – 2.43 (m, 2H), 2.29 – 2.19 (m, 1H). 13C NMR (126 MHz, Chloroform-d) δ 175.26, 137.57, 129.13, 128.39, 127.92, 106.29, 79.33, 51.52, 45.77, 39.72, 34.43, 29.71, 28.23. 50 HRMS: TOF MS AP+ (C12H14BrO3S): Calc. [M + H]+: 388.9390, Found [M + H]+: 388.9391. I-6-4 Synthesis of keto-acid substrates I-45, I-82 to I-92 The ketone substrates were synthesized according to the following general scheme: O Br (1.2 equiv) Br O O O NaH (1.5 equiv) O O I-78 (1 equiv) O n-BuLi (1.1 equiv) O NaH (1.5 equiv) THF, 0 ºC I-77 THF, 0 ºC to r.t. I-76 O O O KOH (5 equiv) R (3 equiv) O OH O EtOH, reflux Grubbs-II (15 mol%) I-80 O DCM, reflux I-79 O O OH R I-81 O I-6-4-1 Synthesis of keto-ester I-77 Br (1.2 equiv) O O NaH (1.5 equiv) O O O n-BuLi (1.1 equiv) O THF, 0 ºC, 100% I-77 I-76 Following the reported procedure26, methyl acetoacetate (4.45 mL, 41.3 mmol) was added dropwise under nitrogen to a suspension of NaH (60% on mineral oil, 2.48 g, 62 mmol) in dry THF (100 mL) at 0 °C. The resulting mixture was stirred for 30 min at this temperature and n-BuLi (18.17 mL, 2.50 M, 45.43 mmol) was added dropwise. The 51 mixture was stirred for another 30 min and allyl bromide (4.28 mL, 49.56 mmol) was added. The reaction stirred for 45 minutes before cautiously, quenched by 2 M HCl (30 mL). The reaction was extracted with diethyl ether (3 x 75 mL). The combined organic layers were washed with saturated NaHCO3 and NaCl. The combined organic extracts dried with anhydrous Na2SO4 and concentrated under reduced pressure at room temperature to give the product I-77 as an orange liquid (6.45 g, 100%). 1H NMR (500 MHz, Chloroform-d) δ 5.79 (ddt, J = 16.9, 10.2, 6.5 Hz, 1H), 5.10 – 4.95 (m, 2H), 3.73 (s, 3H), 3.46 (s, 2H), 2.65 (t, J = 7.3 Hz, 2H), 2.38 – 2.31 (m, 2H). 13C NMR (126 MHz, Chloroform-d) δ 201.87, 167.57, 136.49, 115.61, 52.37, 49.06, 42.06, 27.38. I-6-4-2 Synthesis of di-ester I-79 O Br O I-78 (1 equiv) O O O O NaH (1.5 equiv) O O THF, 0 ºC to r.t. O I-77 65% I-79 O Following the reported procedure26, NaH (60% on mineral oil, 2.48 g, 62 mmol) was added portionwise to a solution of compound I-77 (6.45 g, 41.3 mmol) at 0 °C. The resulting mixture was stirred for 30 min at this temperature and methyl bromoacetate I-78 (3.94 mL, 41.3 mmol) was added dropwise. The reaction was warmed up to the room temperature and stirred for 2 hours before cautiously, quenched by 1 M HCl (50 mL). The reaction was extracted with diethyl ether (3 x 100 mL). The combined organic layers dried 52 with anhydrous Na2SO4 and concentrated under reduced pressure at room temperature. The crude product was then purified by column chromatography (silica, ethyl acetate/hexanes 10% to 30%) leading to the pure product I-79 as a yellow liquid (6.12 g, 65%). 1H NMR (500 MHz, Chloroform-d) δ 5.69 (ddt, J = 16.8, 10.2, 6.5 Hz, 1H), 4.97 – 4.84 (m, 2H), 3.91 (dd, J = 8.4, 6.1 Hz, 1H), 3.64 (s, 3H), 3.56 (s, 3H), 2.88 (dd, J = 17.6, 8.3 Hz, 1H), 2.79 – 2.69 (m, 2H), 2.68 – 2.61 (m, 1H), 2.29 – 2.19 (m, 2H). 13C NMR (126 MHz, Chloroform-d) δ 202.94, 171.64, 168.67, 136.60, 115.22, 53.59, 52.58, 51.87, 41.72, 31.99, 27.22. I-6-4-3 Synthesis of acid I-80 O O O KOH (5 equiv) O OH O EtOH, reflux, 61% I-80 O I-79 O Following the reported procedure26, To a solution of compound I-79 (3.65 g, 16 mmol) in ethanol (75 mL) was added potassium hydroxide ( 4.48 g, 80 mmol) and heated at reflux for 4 hours. The reaction was cooled and concentrated under reduced pressure. Then water (50 mL) was added to the solution and acidified to PH 1 by 2 M HCl. The reaction stirred for 10 minutes and extracted with diethyl ether (3 x 50 mL). The combined organic layers dried with anhydrous Na2SO4 and concentrated under reduced pressure at room temperature. The crude product was then purified by column chromatography 53 (silica, ethyl acetate/hexanes 20% to 40%, acetic acid 0.5% was added to solvent mixture) leading to the pure product I-80 as a yellow solid (1.52 g, 61%). 1H NMR (500 MHz, Chloroform-d) δ 10.44 (br s, 1H), 5.80 (ddt, J = 16.8, 10.2, 6.5 Hz, 1H), 5.10 – 4.89 (m, 2H), 2.75 – 2.61 (m, 4H), 2.56 (t, J = 7.4 Hz, 2H), 2.37 – 2.32 (m, 2H). 13C NMR (126 MHz, Chloroform-d) δ 208.06, 178.90, 136.87, 115.38, 41.69, 36.83, 27.74, 27.66. HRMS: TOF MS ES+ (C8H11O3): Calc. [M - H]- : 155.0708, Found [M - H]- : 155.0711. I-6-4-4 General procedure for Grubbs cross metathesis O O R (3 equiv) OH OH Grubbs-II (15 mol%) R I-80 O DCM, reflux I-81 O Following the reported procedure,43 to a solution of keto-acid I-80 (2 mmol) and vinyl derivatives (6 mmol) in DCM (20 mL) was added Grubbs-II (15 mol%) and heated at reflux overnight under argon. The completion of the reaction monitored by TLC and then, solvent was evaporated under reduced pressure at room temperature. The crude product was then purified by column chromatography (silica, ethyl acetate/hexanes 20% to 30%) leading to the pure derivatives of keto-acid products. 54 I-6-4-5 Analytical data O OH O I-45 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (329 mg, 71% yield) 1H NMR (500 MHz, Chloroform-d) δ 7.36 – 7.26 (m, 4H), 7.23 – 7.19 (m, 1H), 6.42 (dt, J = 15.9, 1.6 Hz, 1H), 6.20 (dt, J = 15.8, 6.9 Hz, 1H), 2.78 – 2.73 (m, 2H), 2.69 – 2.63 (m, 4H), 2.54 – 2.49 (m, 2H). 13C NMR (126 MHz, Chloroform-d) δ 207.94, 178.59, 137.36, 130.86, 128.66, 128.52, 127.12, 126.03, 42.18, 36.92, 27.78, 27.06. HRMS: TOF MS ES+ (C14H15O3): Calc. [M - H]- : 231.1021, Found [M - H]- : 231.1025. O OH O O I-82 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (320 mg, 61% yield) 55 1H NMR (500 MHz, Chloroform-d) δ 7.25 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 6.34 (d, J = 15.8 Hz, 1H), 6.04 (dt, J = 15.8, 6.9 Hz, 1H), 3.79 (s, 3H), 2.76 – 2.70 (m, J, 2H), 2.66 – 2.60 (m, 4H), 2.51 – 2.44 (m, 2H). 13C NMR (126 MHz, cdcl3) δ 208.12, 178.70, 158.82, 130.19, 127.13, 126.45, 113.92, 55.28, 42.34, 36.91, 27.76, 27.07. HRMS: TOF MS ES+ (C15H17O4): Calc. [M - H]- : 261.1127, Found [M - H]- : 261.1130. O OH O CF3 I-84 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (252 mg, 42% yield) 1H NMR (500 MHz, Chloroform-d) δ 10.65 (br s, 1H) 7.53 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 6.43 (d, J = 15.7 Hz, 1H), 6.29 (dt, J = 15.8, 6.7 Hz, 1H), 2.78 – 2.70 (M, 2H), 2.70 – 2.62 (m, 4H), 2.57 – 2.48 (m, 2H). 13C NMR (126 MHz, Chloroform-d) δ 207.75, 178.91, 140.87, 131.55, 129.65, 128.82 (q, J = 32.3 Hz), 126.17, 125.42 (q, J = 3.8 Hz), 41.76, 36.86, 27.75, 26.96. 19F NMR (470 MHz, Chloroform-d) δ -62.42 (s, 3F). HRMS: TOF MS ES+ (C15H14F3O3): Calc. [M - H]- : 299.0895, Found [M - H]- : 299.0899. 56 O OH O I-85 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (354 mg, 72% yield) 1H NMR (500 MHz, Chloroform-d) δ 10.90 (br s, 1H), 7.24 (d, J = 7.9 Hz, 2H), 7.11 (d, J = 7.8 Hz, 2H), 6.38 (d, J = 15.8 Hz, 1H), 6.14 (dt, J = 15.8, 6.8 Hz, 1H), 2.74 (t, J = 6.4 Hz, 2H), 2.68 – 2.59 (m, 4H), 2.49 (q, J = 7.5 Hz, 2H), 2.33 (s, 3H). 13C NMR (126 MHz, Chloroform-d) δ 208.17, 178.71, 136.84, 134.60, 130.66, 129.22, 127.64, 125.94, 42.24, 36.95, 27.86, 27.09, 21.17. HRMS: TOF MS ES+ (C15H17O3): Calc. [M - H]- : 245.1178, Found [M - H]- : 245.1176. O OH O F I-86 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (275 mg, 55% yield) 1H NMR (500 MHz, Chloroform-d) δ 10.16 (br s, 1H), 7.28 (dd, J = 8.5, 5.5 Hz, 2H), 6.97 (t, J = 8.6 Hz, 2H), 6.36 (d, J = 15.8 Hz, 1H), 6.10 (dt, J = 15.8, 6.8 Hz, 1H), 2.74 (t, J = 6.2 Hz, 2H), 2.68 – 2.60 (m, 4H), 2.49 (q, J = 7.1 Hz, 2H). 57 13C NMR (126 MHz, Chloroform-d) δ 207.93, 178.79, 162.01 (d, J = 246.0 Hz), 133.52 (d, J = 3.3 Hz), 129.68, 128.39 (d, J = 2.3 Hz), 127.47 (d, J = 7.9 Hz), 115.34 (d, J = 21.5 Hz), 42.10, 36.89, 27.75, 26.96. 19F NMR (470 MHz, Chloroform-d) δ -115.35 (m, 1F). HRMS: TOF MS ES+ (C14H14FO3): Calc. [M - H]- : 249.0894, Found [M - H]- : 249.0902. O OH O O O I-87 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (330 mg, 57% yield) 1H NMR (500 MHz, Chloroform-d) δ 7.32 (d, J = 8.5 Hz, 2H), 7.01 (d, J = 8.5 Hz, 2H), 6.39 (d, J = 15.8 Hz, 1H), 6.14 (dt, J = 15.8, 6.9 Hz, 1H), 2.79 – 2.73 (m, 2H), 2.69 – 2.61 (m, 4H), 2.50 (q, J = 7.0 Hz, 2H), 2.29 (s, 3H). 13C NMR (126 MHz, Chloroform-d) δ 209.46, 175.05, 169.79, 149.78, 135.38, 129.39, 128.99, 126.47, 126.47, 121.32, 41.44, 36.61, 27.26, 26.69, 19.50. HRMS: TOF MS ES+ (C16H17O5): Calc. [M - H]- : 289.1076, Found [M - H]- : 289.1072. O OH O I-88 58 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (344 mg, 61% yield) 1H NMR (500 MHz, Chloroform-d) δ 7.78 (t, 3H), 7.68 (s, 1H), 7.56 (dd, J = 8.5, 1.8 Hz, 1H), 7.49 – 7.39 (m, 2H), 6.58 (d, J = 15.9 Hz, 1H), 6.33 (dt, J = 15.9, 6.8 Hz, 1H), 2.80 (t, J = 6.4 Hz, 2H), 2.74 – 2.65 (m, 4H), 2.58 (q, J = 7.2 Hz, 2H). 13C NMR (126 MHz, cdcl3) δ 207.92, 178.18, 134.82, 133.64, 132.76, 130.98, 129.11, 128.11, 127.89, 127.63, 126.18, 125.66, 125.62, 123.48, 42.19, 36.94, 27.68, 27.16. O OH O I-90 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (229 mg, 54% yield) 1H NMR (500 MHz, Chloroform-d) δ 5.46 (dt, J = 15.6, 1.4 Hz, 1H), 5.28 (dt, J = 15.5, 6.6 Hz, 1H), 2.73 – 2.68 (m, 2H), 2.66 – 2.60 (m, 2H), 2.50 (t, J = 7.5 Hz, 3H), 2.33 – 2.23 (m, 3H), 0.96 (s, 12H). 13C NMR (126 MHz, Chloroform-d) δ 208.50, 176.21, 142.76, 122.59, 42.75, 36.99, 32.80, 29.64, 27.37, 26.89. HRMS: TOF MS ES+ (C12H19O3): Calc. [M - H]- : 211.1334, Found [M - H]- : 211.1330. 59 O OH O I-91 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (180 mg, 38% yield) 1H NMR (500 MHz, Chloroform-d) δ 5.44 – 5.28 (m, 2H), 2.73 (t, J = 6.9Hz, 2H), 2.7 – 2.62 (m, 2H), 2.51 (t, J = 7.6 Hz, 2H), 2.31 – 2.24 (m, 2H), 1.92 – 1.84 (m, 1H), 1.71 – 1.63 (m, 4H), 1.29 – 0.98 (m, 6H). HRMS: TOF MS ES+ (C14H21O3): Calc. [M - H]- : 237.1490, Found [M - H]- : 237.1491. O OH S O I-92 The title compound was prepared according to the general procedure at 2 mmol scale. Product was isolated as a white solid (180 mg, 59% yield) 1H NMR (500 MHz, Chloroform-d) δ 11.34 (s, 1H), 7.08 (d, J = 5.3 Hz, 1H), 6.94 – 6.90 (m, 1H), 6.87 (t, J = 2.7 Hz, 1H), 6.52 (d, J = 15.7 Hz, 1H), 6.05 – 6.97 (m, 1H), 2.72 (t, J = 6.4 Hz, 2H), 2.65 – 2.57 (m, 4H), 2.45 (q, J = 7.0 Hz, 2H). 13C NMR (126 MHz, Chloroform-d) δ 207.93, 178.66, 142.51, 128.58, 127.27, 124.73, 124.10, 123.48, 41.97, 36.93, 27.86, 26.81. 60 HRMS: TOF MS ES+ (C12H13O3S): Calc. [M - H]- : 237.0585, Found [M - H]- : 237.0591. O O OH I-112 The title compound was prepared according to the procedure I-6-4-3 at 2 mmol scale. Product was isolated as a white solid (261 mg, 53% yield) 1H NMR (500 MHz, Chloroform-d) δ 10.80 (s, 1H), 7.37 – 7.26 (m, 4H), 7.24 – 7.18 (m, 1H), 6.41 (dt, J = 15.8, 1.6 Hz, 1H), 6.19 (dt, J = 15.8, 6.8 Hz, 1H), 2.60 (t, J = 7.5 Hz, 2H), 2.57 – 2.46 (m, 4H), 2.41 (t, J = 7.2 Hz, 2H), 1.93 (p, J = 7.2 Hz, 2H). 13C NMR (126 MHz, Chloroform-d) δ 209.40, 179.52, 137.36, 130.82, 128.76, 128.53, 127.14, 126.02, 42.29, 41.48, 33.00, 27.10, 18.50. HRMS: TOF MS ES+ (C15H17O3): Calc. [M - H]- : 245.1178, Found [M - H]- : 245.1174. O OH O I-113 The title compound was prepared according to the procedure I-6-4-3 at 2 mmol scale. Product was isolated as a white solid (218 mg, 47% yield) 1H NMR (500 MHz, Chloroform-d) δ 11.12 (s, 1H), 7.42 – 7.25 (m, 5H), 5.30 (s, 1H), 5.07 (d, J = 1.6 Hz, 1H), 2.81 (t, J = 7.85 Hz, 2H), 2.72 – 2.58 (m, 6H). 61 13C NMR (126 MHz, Chloroform-d) δ 208.02, 178.73, 146.99, 140.49, 128.44, 127.64, 126.10, 112.92, 41.36, 36.93, 29.18, 27.74. HRMS: TOF MS ES+ (C14H15O3): Calc. [M - H]- : 231.1021, Found [M - H]- : 231.1017. I-6-5 Synthesis of the amine derivative of dihydroquinidine I-114 N N N HO Ph3P (1.2 equiv.) H DIAD (1.2 equiv.) N3 Ph3P (1.8 equiv.) H 2N H H O O O DPPA (1.2 equiv.) H2O, THF DCM N N N I-50 I-114 Following the reported procedure,44 to a solution of dihydroquinidine, DHQD (6g, 18.4 mmol) in DCM (36 mL) was added Ph3P (5.79 g, 22.05 mmol). The reaction mixture was stirred at room temperature for 30 minutes under nitrogen balloon. The solution cooled to 0 °C and the diisopropyl azodicarboxylate, DIAD (4.33 mL, 22.05 mmol) was added dropwise and kept the solution temperature below 5 °C. After 5 minutes, a solution of diphenyl phosphoryl azide, DPPA (4.75 mL, 22.05 mmol) in DCM (8 mL) was added dropwise while the solution temperature kept around 0 °C. The mixture was warmed up to 20 °C and stirred for 2 hours to form the azide derivative intermediate. Next, H2O (8.1 mL) and a solution of Ph3P (8.7 g, 33.12 mmol) in DCM (8 mL) was added and the reaction stirred overnight at room temperature. The reaction quenched by 3N HCl to pH 2.2 and the product was in upper aqueous layer which washed with DCM. After discarding the organic layer, 28% aqueous ammonia was added to the aqueous layer to adjust pH to above 10. The solution was extracted with DCM (3 x 20 mL). The combined organic layers 62 dried with anhydrous Na2SO4 and concentrated under reduced pressure at room temperature. The crude product was then purified by column chromatography (silica, ethyl acetate/methanol/ammonium hydroxide 50:49.5:0.5%) leading to the pure product I-114 as a yellow oil (3.65 g, 61%). 1H NMR (500 MHz, Methanol-d4) δ 8.69 (d, J = 4.7 Hz, 1H), 7.97 (d, J = 9.2 Hz, 1H), 7.69 – 7.61 (m, 2H), 7.46 (dd, J = 9.2, 2.7 Hz, 1H), 4.86 – 4.78 (d, 10.1 Hz,1H), 4.01 (s, 3H), 3.35 (s, 1H), 3.14 – 2.95 (m, 4H), 2.87 – 2.78 (m, 1H), 1.55 – 1.38 (m, 6H), 1.06 – 0.98 (m, 1H), 0.90 (t, J = 7.1, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.39, 148.22, 147.00, 143.63, 131.63, 130.11, 128.90, 122.23, 101.04, 62.65, 54.77, 48.98, 48.61, 48.45, 37.04, 26.56, 25.80, 25.50, 24.31, 10.77. I-6-6 General procedure for the synthesis of cinchona alkaloid derivatives N R5 R5 N H Y R4 N R4 N Y H C NaH (2 equiv.) H X R6 R1 R3 DCM, r.t. R3 R1 X R6 R2 R2 N N X= O, S Y= OH, NH2 Following the reported procedure,24 NaH (60% on mineral oil, 80 mg, 2 mmol) was added to a solution of cinchona derivative (1 mmol) and isocyanate/isothiocyanate derivative (1 mmol) in THF (5 mL). The reaction was stirred at room temperature for overnight and the completion of the reaction monitored by TLC. After quenching the reaction with water (10 mL), the solution was extracted with DCM (3 x 20 mL). The 63 combined organic layers washed with NaCl, dried with anhydrous Na2SO4 and concentrated under reduced pressure at room temperature. The crude product was then purified by column chromatography (silica, methanol/DCM 10%) leading to the pure catalyst products as white solids. O H N N O H O S O N I-51 The compound existed as a mixture of rotamers. 1H NMR (500 MHz, DMSO-d6) δ 10.56 – 10.47 (m, 1H), 8. 78 – 8.67 (m, 1H), 7.99 – 7.90 (m, 1H), 7.57 – 7.06 (m, 5H), 6.63 – 6.45 (m, 2H), 3.82 – 3.47 (m, 9H), 3.19 – 3.10 (m, 1H), 2.78 – 2.60 (m, 2H), 2.53 – 2.43 (m, 2H), 1.70 – 1.36 (m, 5H), 1.31 – 1.21 (m, 3H), 0.90 – 0.79 (m, 3H). 13C NMR (126 MHz, DMSO-d6) δ 190.23, 188.36, 160.00, 159.62, 157.60, 157.41, 155.21, 148.00, 147.87, 144.96, 144.56, 144.51, 131.69, 131.65, 129.38, 128.39, 127.62, 127.27, 121.90, 121.72, 120.46, 120.24, 120.09, 118.99, 104.81, 102.96, 99.51, 99.32, 79.77, 79.66, 77.77, 60.07, 59.78, 56.08, 55.98, 55.83, 55.78, 55.66, 55.56, 50.65, 50.59, 49.39, 49.36, 37.47, 37.36, 27.35, 27.10, 26.08, 25.85, 25.54, 25.29, 23.81, 23.66, 12.43, 12.42. HRMS: TOF MS ES+ (C29H36N3O4S): Calc. [M + H]+: 522.2427, Found [M + H]+: 522.2421. 64 O H H N N N H O O O N I-52 1H NMR (500 MHz, Methanol-d4) δ 8.61 (d, J = 4.7 Hz, 1H), 7.92 (d, J = 9.2 Hz, 1H), 7.81 (d, J = 2.7 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 4.7 Hz, 1H), 7.34 (dd, J = 9.3, 2.6 Hz, 1H), 6.39 (d, J = 2.6 Hz, 1H), 6.30 (dd, J = 8.9, 2.6 Hz, 1H), 5.59 (br s, 1H), 3.96 (s, 3H), 3.64 (s, 3H), 3.60 (s, 3H), 3.11 – 3.00 (m, 1H), 2.91 – 12.71 (m, 4H), 1.46 – 1.15 (m, 7H), 1.05 – 0.95 (m, 1H), 0.87 (t, J = 9.6 Hz, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.21, 156.35, 155.67, 149.76, 147.69, 147.00, 143.71, 130.11, 128.73, 122.35, 121.81, 120.22, 119.28, 103.58, 101.61, 98.14, 59.89, 54.95, 54.80, 54.54, 48.91, 48.85, 37.04, 26.69, 25.73, 24.88, 19.83, 11.04. HRMS: TOF MS ES+ (C29H37N4O4): Calc. [M + H]+: 505.2815, Found [M + H]+: 505.2812. O H H N N N H O S O N I-53 1H NMR (500 MHz, Methanol-d4) δ 8.58 (d, J = 4.7 Hz, 1H), 8.02 (br s, 1H), 7.91 (d, J = 9.2 Hz, 1H), 7.44 (d, J = 4.7 Hz, 1H), 7.39 (dd, J = 9.2, 2.6 Hz, 2H), 6.49 (d, J = 2.6 Hz, 1H), 6.45 (dd, J = 8.7, 2.6 Hz, 1H), 6.21 (br s, 1H), 3.97 (s, 3H), 3.75 (s, 3H), 3.54 (s, 3H), 65 3.18 (ddd, J = 10.6, 9.7, 9.3 Hz, 1H), 2.95 (d, J = 8.4 Hz, 2H), 2.84 (m, 2H), 1.54 – 1.32 (m, 6H), 1.13 (dd, J = 12.5, 8.2 Hz, 1H), 0.89 (t, J = 7.2 Hz, 3H). 13C NMR (126 MHz, Methanol-d4) δ 181.20, 159.37, 158.01, 154.24, 147.33, 146.83, 143.63, 129.75, 128.81, 127.47, 122.38, 119.80, 119.35, 103.97, 102.60, 98.50, 59.88, 54.98, 54.61, 54.58, 49.27, 48.60, 37.16, 26.68, 25.82, 24.74, 10.93. HRMS: TOF MS ES+ (C29H37N4O3S): Calc. [M + H]+: 521.2578, Found [M + H]+: 521.2586. O H N N O H O O O N I-54 1H NMR (500 MHz, Methanol-d4) δ 8.65 (d, J = 4.6 Hz, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.63 – 7.42 (m, 3H), 7.38 (dd, J = 9.3, 2.6 Hz, 1H), 6.68 – 6.27 (m, 3H), 3.94 (s, 3H), 3.75 (s, 3H), 3.66 (s, 3H), 3.20 (br s, 1H), 2.89 – 2.59 (m, 4H), 2.07 – 1.90 (m, 1H), 1.59 – 1.24 (m, 7H), 0.93 – 0.82 (m, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.41, 157.28, 153.58, 151.33, 146.79, 145.02, 143.65, 130.20, 126.96, 122.34, 121.91, 119.79, 118.56, 103.72, 101.11, 98.39, 73.17, 58.78, 55.09, 54.87, 54.55, 50.34, 49.37, 36.87, 26.32, 25.87, 25.03, 21.74, 11.09. HRMS: TOF MS ES+ (C29H36N3O5): Calc. [M + H]+: 506.2655, Found [M + H]+: 506.2652. 66 H N CF3 N O H O O CF3 N I-55 1H NMR (500 MHz, Methanol-d4) δ 8.65 (d, J = 4.6 Hz, 1H), 8.06 (s, 2H), 7.91 (d, J = 9.2 Hz, 1H), 7.57 (d, J = 4.7 Hz, 1H), 7.54 (d, J = 2.7 Hz, 1H), 7.49 (s, 1H), 7.35 (dd, J = 9.2, 2.6 Hz, 1H), 6.75 (d, J = 5.4 Hz, 1H), 3.98 (s, 3H), 3.37 – 3.27 (m, 1H), 2.93 – 2.63 (m, 4H), 2.06 – 1.99 (m, 1H), 1.69 – 1.63 (m, 1H), 1.56 – 1.36 (m, 6H), 0.85 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.53, 152.81, 146.72, 144.38, 143.65, 140.80, 131.86 (q, J = 33.2 Hz), 130.17, 126.91, 123.14 (q, J = 272, Hz), 122.38, 118.50, 117.87, 115.45, 101.03, 73.57, 58.88, 55.07, 50.33, 49.30, 36.72, 26.05, 25.66, 24.77, 21.79, 10.87. 19F NMR (470 MHz, Methanol-d4) δ -64.48 (s, 6F). HRMS: TOF MS ES+ (C29H30F6N3O3): Calc. [M + H]+: 582.219, Found [M + H]+: 582.2197. H N CF3 N O H S O CF3 N I-56 67 1H NMR (500 MHz, Methanol-d4) δ 8.67 (d, J = 4.7 Hz, 1H), 8.33 (br s, 2H), 7.91 (d, J = 9.2 Hz, 1H), 7.74 – 7.51 (m, 3H), 7.48 (d, J = 6.4 Hz, 1H), 7.35 (dd, J = 9.2, 2.6 Hz, 1H), 5.09 (br s, 2H), 3.95 (s, 3H), 3.44 (ddd, J = 9.2, 8.5, 7.0 Hz, 1H), 2.91 – 2.57 (m, 4H), 2.14 – 1.94 (m, 1H), 1.72 – 1.30 (m, 7H), 0.91 – 0.70 (m, 3H). 13C NMR (126 MHz, Methanol-d4) δ 187.19, 158.42, 146.73, 144.18, 143.76, 140.51, 131.68, 130.11, 127.25, 123.15, 122.40, 122.15, 119.10, 117.81, 101.56, 77.18, 59.49, 55.06, 50.45, 49.13, 36.80, 26.17, 25.64, 24.96, 22.50, 10.87. 19F NMR (470 MHz, Methanol-d4) δ -64.30 (s, 6F). HRMS: TOF MS ES+ (C29H30F6N3O2S): Calc. [M + H]+: 598.1963, Found [M + H]+: 598.1964. O H N N O H O O N I-57 1H NMR (500 MHz, Methanol-d4) δ 8.63 (d, J = 4.7 Hz, 1H), 7.93 (d, J = 9.2 Hz, 1H), 7.60 (br s, 1H), 7.54 (d, J = 4.7 Hz, 1H), 7.50 (d, J = 2.7 Hz, 1H), 7.37 (dd, J = 9.2, 2.7 Hz, 1H), 6.73 (s, 2H), 6.61 (d, J = 5.4 Hz, 1H), 3.94 (s, 3H), 3.74 (s, 3H), 3.16 (td, J = 8.9, 5.3 Hz, 1H), 2.84 – 2.56 (m, 4H), 2.13 (s, 3H), 1.98 – 1.90 (m, 1H), 1.60 – 1.54 (m, 1H), 1.49 – 1.24 (m, 6H), 0.89 – 0.81 (m, 3H). 68 13C NMR (126 MHz, Methanol-d4) δ 158.43, 153.01, 147.23, 146.79, 144.96, 143.65, 130.19, 129.71, 127.00, 126.37, 124.03, 122.33, 120.46, 118.59, 110.17, 101.08, 73.40, 58.77, 55.05, 54.92, 50.32, 49.35, 36.87, 26.37, 25.86, 25.02, 21.86, 19.67, 11.03. HRMS: TOF MS ES+ (C29H36N3O4): Calc. [M + H]+: 490.2706, Found [M + H]+: 490.2694. O H N N O H S O N I-58 The compound existed as a mixture of rotamers. 1H NMR (500 MHz, Methanol-d4) δ 8.74 – 8.60 (m, 1H), 7.99 – 7.90 (m, 1H), 7.71 – 7.29 (m, 4H), 7.10 – 6.73 (m, 2H), 4.04 – 3.49 (m, 6H), 3.36 – 3.15 (m, 1H), 2.92 – 2.43 (m, 4H), 2.30 – 2.04 (m, 3H), 1.90 – 1.76 (m, 1H), 1.60 – 1.19 (m, 6H), 1.09 – 0.64 (m, 4H). 13C NMR (126 MHz, Methanol-d4) δ 188.11, 187.34, 158.27, 150.82, 149.88, 146.79, 144.88, 144.49, 143.84, 130.25, 129.71, 129.23, 128.22, 127.21, 127.04, 126.76, 125.38, 122.35, 119.62, 119.06, 111.28, 110.82, 101.83, 80.32, 77.31, 59.12, 55.24, 55.08, 54.88, 53.77, 53.74, 50.46, 49.21, 36.97, 26.41, 25.71, 25.22, 24.58, 22.20, 19.63, 11.35, 11.33. HRMS: TOF MS ES+ (C29H36N3O3S): Calc. [M + H]+: 506.2477, Found [M + H]+: 506.2475. 69 O H N N O H O O O N I-59 1H NMR (500 MHz, Methanol-d4) δ 8.65 (d, J = 4.6 Hz, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.60 (d, J = 4.7 Hz, 1H), 7.50 (d, J = 2.7 Hz, 1H), 7.45 (br s, 1H), 7.41 (dd, J = 9.3, 2.6 Hz, 1H), 6.84 (d, J = 8.9 Hz, 1H), 6.62 (d, J = 5.4 Hz, 1H), 6.57 – 6.52 (m, 1H), 3.97 (s, 3H), 3.79 (s, 3H), 3.65 (s, 3H), 3.25 (td, J = 9.0, 5.3 Hz, 1H), 2.91 – 2.65 (m, 4H), 2.05 – 1.96 (m, 1H), 1.71 – 1.64 (m, 1H), 1.58 – 1.36 (m, 6H), 0.93 – 0.84 (m, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.49, 153.73, 152.93, 146.75, 144.85, 143.59, 130.10, 127.43, 126.94, 122.37, 118.56, 111.05, 107.74, 100.98, 73.54, 58.74, 55.33, 55.00, 54.58, 50.34, 49.35, 36.88, 26.28, 25.88, 24.98, 21.81, 10.91. HRMS: TOF MS ES+ (C29H36N3O5): Calc. [M + H]+: 506.2655, Found [M + H]+: 506.2651. H N N O H O O O N I-60 1H NMR (500 MHz, Methanol-d4) δ 8.70 (d, J = 4.6 Hz, 1H), 7.96 (d, J = 9.1 Hz, 1H), 7.70 – 7.47 (m, 2H), 7.43 (dd, J = 9.2, 2.6 Hz, 1H), 7.10 (d, J = 8.6 Hz, 1H), 6.86 – 6.59 (m, 70 3H), 3.97 (s, 3H), 3.71 (s, 3H), 3.32 – 3.25 (m, 1H), 3.03 – 2.66 (m, 4H), 2.18 (s, 3H), 1.80 – 1.25 (m, 8H), 1.01 – 0.88 (m, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.49, 157.96, 154.90, 146.71, 145.23, 143.65, 134.92, 130.09, 128.20, 126.97, 126.91, 122.42, 118.39, 115.30, 111.15, 101.02, 73.51, 58.77, 55.01, 54.35, 50.45, 49.34, 36.96, 26.36, 25.91, 25.02, 21.58, 16.91, 11.04. HRMS: TOF MS ES+ (C29H36N3O4): Calc. [M + H]+: 490.2706, Found [M + H]+: 490.2695. O H N N O H O O O O N ` I-62 The compound existed as a mixture of rotamers. 1H NMR (500 MHz, Methanol-d4) δ 8.72 (d, J = 4.6 Hz, 1H), 7.95 (d, J = 9.2 Hz, 1H), 7.65 (br s, 1H), 7.49 – 7.32 (m, 2H), 6.68 (m, 1H), 6.24 (m, 2H), 3.96 – 3.66 (m, 12H), 3.47 – 3.21 (m, 1H), 3.09 – 2.65 (m, 4H), 1.82 – 1.33 (m, 7H), 0.97 – 0.64 (m, 4H). 13C NMR (126 MHz, cd3od) δ 160.60, 160.36, 158.50, 157.13, 155.43, 155.08, 146.71, 146.58, 144.29, 143.61, 130.18, 126.73, 126.28, 122.40, 118.61, 106.82, 100.99, 90.58, 74.29, 72.57, 58.80, 58.15, 55.17, 55.01, 54.61, 53.56, 50.37, 50.19, 49.39, 48.19, 48.02, 47.85, 47.67, 47.50, 47.33, 47.16, 36.47, 36.21, 25.70, 25.59, 25.17, 24.92, 24.70, 23.84, 20.83, 19.75, 11.11, 10.97. 71 HRMS: TOF MS ES+ (C30H38N3O6): Calc. [M + H]+: 536.2759, Found [M + H]+: 536.2761. H N O N O H O O O O N I-63 1H NMR (500 MHz, Methanol-d4) δ 8.67 (d, J = 4.6 Hz, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.57 (d, J = 4.7 Hz, 1H), 7.53 (d, J = 2.7 Hz, 1H), 7.42 (dd, J = 9.2, 2.6 Hz, 1H), 6.81 (s, 2H), 6.68 (d, J = 5.4 Hz, 1H), 3.99 (s, 3H), 3.75 (s, 6H), 3.68 (s, 3H), 3.34 (td, J = 9.0, 5.3 Hz, 1H), 3.01 – 2.70 (m, 4H), 2.11 – 2.03 (m, 1H), 1.78 – 1.72 (m, 1H), 1.60 – 1.48 (m, 5H), 1.29 – 1.22 (m, 1H), 0.91 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.55, 153.18, 152.98, 146.75, 144.78, 143.63, 134.80, 130.14, 126.91, 122.39, 118.48, 102.46, 101.06, 96.16, 72.82, 59.78, 58.94, 55.07, 55.06, 50.33, 49.29, 36.69, 25.94, 25.70, 24.75, 21.74, 10.89. HRMS: TOF MS ES+ (C30H38N3O6): Calc. [M + H]+: 536.2761, Found [M + H]+: 536.2769. O H N N O H O O O N I-64 1H NMR (500 MHz, Methanol-d4) δ 8.66 (d, J = 4.6 Hz, 1H), 7.95 (d, J = 9.2 Hz, 1H), 7.60 (d, J = 4.7 Hz, 1H), 7.56 – 7.42 (m, 2H), 7.40 (dd, J = 9.2, 2.6 Hz, 1H), 6.71 (d, J = 4.4 72 Hz, 1H), 6.52 (s, 1H), 6.40 – 6.29 (m, 1H), 4.57 – 4.39 (m, 2H), 3.96 (s, 3H), 3.37 – 3.28 (m, 1H), 3.05 – 2.72 (m, 4H), 2.16 – 2.05 (m, 1H), 1.77 – 1.15 (m, 19H), 0.90 (m, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.58, 155.46, 153.15, 149.56, 146.77, 144.38, 143.66, 130.24, 126.70, 122.47, 122.31, 120.45, 118.47, 106.46, 102.79, 101.02, 72.98, 70.91, 69.84, 58.55, 55.24, 50.42, 49.42, 36.48, 26.60, 25.73, 25.43, 24.84, 21.11, 21.06, 11.08. HRMS: TOF MS ES+ (C33H44N3O5): Calc. [M + H]+: 562.3281, Found [M + H]+: 562.3283. O H N N O H O O O N I-66 1H NMR (500 MHz, Methanol-d4) δ 8.65 (d, J = 4.7 Hz, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.62 – 7.43 (m, 3H), 7.41 (dd, J = 9.2, 2.5 Hz, 1H), 6.68 – 6.31 (m, 3H), 3.96 – 3.84 (m, 2H), 3.76 (s, 3H), 3.68 (s, 3H), 3.29 – 3.28 (m, 1H), 2.95 – 2.65 (m, 4H), 2.15 – 1.97 (m, 2H), 1.71 – 1.34 (m, 7H), 1.06 (d, J = 2.9 Hz, 3H), 1.05 (d, J = 2.9 Hz, 3H), 0.95 – 0.85 (m, 3H). 13C NMR (126 MHz, Methanol-d4) δ 158.00, 157.44, 153.63, 151.45, 146.66, 144.75, 143.55, 130.12, 127.00, 122.63, 122.18, 119.71, 118.53, 103.72, 101.68, 98.38, 74.60, 72.77, 58.82, 54.83, 54.52, 50.31, 49.35, 36.70, 28.13, 26.07, 25.83, 24.96, 21.64, 18.31, 11.00. 73 HRMS: TOF MS ES+ (C32H42N3O5): Calc. [M + H]+: 548.3127, Found [M + H]+: 548.3124. O N H N O H O O O N I-67 The compound existed as a mixture of rotamers. 1H NMR (500 MHz, Methanol-d4) δ 8.67 (d, J = 4.6 Hz, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.65 – 7.39 (m, 4H), 6.67 – 6.34 (m, 3H), 3.97 (s, 3H), 3.80 (s, 3H), 3.72 (s, 3H), 3.38 – 3,23 (m, 2H), 3.06 (t, J = 11.9 Hz, 1H), 2.80 – 2.61 (m, 1H), 2.42 – 2.31 (m, 1H), 1.97 – 1.45 (m, 6H), 1.31 – 1.18 (m, 2H), 0.86 – 0.75 (m, 3H). 13C NMR (126 MHz, cd3od) δ 158.57, 158.53, 157.72, 153.90, 152.02, 146.71, 144.94, 143.61, 143.59, 130.15, 130.10, 126.75, 123.00, 122.37, 119.57, 118.47, 118.37, 103.72, 101.02, 98.40, 73.61, 58.70, 57.80, 57.34, 55.12, 55.09, 54.79, 54.52, 48.13, 47.96, 47.79, 47.62, 47.45, 47.28, 47.11, 43.38, 42.63, 36.87, 27.12, 27.00, 25.65, 25.48, 25.12, 21.62, 10.90, 10.83. HRMS: TOF MS ES+ (C29H36N3O5): Calc. [M + H]+: 506.2655, Found [M + H]+: 506.2653. O H N N H O O O N I-68 74 1H NMR (500 MHz, Methanol-d4) δ 8.64 (d, J = 4.6 Hz, 1H), 7.95 (d, J = 9.2 Hz, 1H), 7.83 – 7.77 (m, 2H), 7.57 (d, J = 4.7 Hz, 1H), 7.40 (dd, J = 9.2, 2.6 Hz, 1H), 6.55 (d, J = 2.3 Hz, 1H), 6.49 (dd, J = 8.8, 2.3 Hz, 1H), 5.76 – 5.59 (m, 1H), 3.96 (s, 3H), 3.90 (s, 3H), 3.74 (s, 3H), 3.36 – 3.28 (m, 1H), 3.05 – 2.89 (m, 3H), 2.82 – 2.75 (m, 1H), 1.53 – 1.32 (m, 6H), 1.26 – 1.18 (m, 1H), 1.01 – 0.94 (m, 1H), 0.86 (t, J = 7.1Hz, 3H). 13C NMR (126 MHz, Methanol-d4) δ 165.86, 164.07, 159.54, 158.14, 146.97, 146.79, 143.73, 132.61, 130.16, 128.44, 122.25, 119.68, 113.43, 105.43, 101.52, 98.09, 59.77, 55.28, 54.80, 54.68, 48.89, 37.03, 26.64, 25.70, 25.68, 24.80, 10.95. HRMS: TOF MS ES+ (C29H36N3O4): Calc. [M + H]+: 490.2706, Found [M + H]+: 490.2705. O S N N H H N O I-69 1H NMR (500 MHz, Methanol-d4) δ 7.44 (d, J = 8.7 Hz, 1H), 6.58 (d, J = 2.6 Hz, 1H), 6.50 (dd, J = 8.7, 2.6 Hz, 1H), 4.96 – 4.68 (m, 1H), 4.28 – 4.11 (m, 1H), 3.79 (s, 3H), 3.78 (s, 3H), 2.64 – 2.51 (m, 1H), 2.32 (s, 6H), 1.91 – 1.63 (m, 3H), 1.34 – 1.07 (m, 4H). 13C NMR (126 MHz, cd3od) δ 180.23, 159.31, 154.39, 127.62, 119.33, 104.22, 98.76, 66.02, 55.41, 55.14, 54.95, 53.90, 39.44, 32.64, 24.82, 24.62, 22.56. HRMS: TOF MS ES+ (C17H28N3O2S): Calc. [M + H]+: 338.1902, Found [M + H]+: 338.1903. 75 O O N N H H N O I-70 1H NMR (500 MHz, Methanol-d4) δ 7.76 (d, J = 8.8 Hz, 1H), 6.54 (d, J = 2.7 Hz, 1H), 6.44 (dd, J = 8.8, 2.7 Hz, 1H), 3.82 (s, 3H), 3.74 (s, 3H), 3.70 – 3.62 (m, 1H), 2.60 (td, J = 10.8, 3.3 Hz, 1H), 2.47 (s, 6H), 2.11 – 2.03 (m, 1H), 1.96 – 1.89 (m, 1H), 1.83 – 1.75 (m, 1H), 1.72 – 1.66 (m, 1H), 1.34 – 1.20 (m, 4H). 13C NMR (126 MHz, Methanol-d4) δ 156.81, 156.04, 150.39, 150.31, 121.76, 121.70, 121.09, 120.96, 103.75, 98.24, 67.14, 54.95, 54.65, 49.99, 49.90, 39.25, 33.59, 24.53, 24.45, 22.86. HRMS: TOF MS ES+ (C17H28N3O3): Calc. [M + H]+: 322.2131, Found [M + H]+: 322.2125. O O O N H N O I-71 1H NMR (500 MHz, Methylene Chloride-d2) δ 7.92 (d, J = 8.5 Hz, 1H), 6.53 – 6.45 (m, 2H), 4.73 (td, J = 10.0, 4.4 Hz, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 2.57 (ddd, J = 11.3, 10.0, 3.7 Hz, 1H), 2.33 (s, 6H), 2.22 – 2.14 (m, 1H), 1.93 – 1.86 (m, 1H), 1.81 – 1.70 (m, 2H), 1.43 – 1.16 (m, 4H). 76 13C NMR (126 MHz, Methylene Chloride-d2) δ 155.82, 153.29, 149.31, 121.33, 119.09, 103.73, 98.53, 73.07, 66.05, 55.59, 55.35, 40.25, 32.25, 24.74, 24.27, 23.00. HRMS: TOF MS ES+ (C17H27N2O4): Calc. [M + H]+: 323.1971, Found [M + H]+: 323.1961. 77 I-6-7 General data I-6-7-1 Crystal data for I-46a Experimental. Single colorless needle-shaped crystals of I-46a were used as received. A suitable crystal 0.31×0.06×0.05 mm3 was selected and mounted on a nylon loop with paratone oil on a Bruker APEX-II CCD diffractometer. The crystal was kept at a steady T = 173(2) K during data collection. The structure was solved with the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program using the Intrinsic Phasing solution method and by using Olex2 (Dolomanov et al., 2009) as the graphical interface. The model was refined with version 2018/3 of ShelXL (Sheldrick, Acta Cryst. A64 2008, 112-122) using Least Squares minimization. Crystal Data. C14H15BrO3, Mr = 311.17, monoclinic, P21/c (No. 14), a = 5.6807(4) Å, b = 17.3739(9) Å, c = 26.0214(15) Å, b = 90.501(4)°, a = g = 90°, V = 2568.1(3) Å3, T = 173(2) K, Z = 8, Z' = 2, µ(CuKa) = 4.355, 26476 reflections measured, 5018 unique (Rint = 0.0710) which were used in all calculations. The final wR2 was 0.0855 (all data) and R1 was 0.0337 (I > 2(I)). 78 Compound I-46a CCDC 1939189 Formula C14H15BrO3 Dcalc./ g cm-3 1.610 µ/mm-1 4.355 Formula Weight 311.17 Color colorless Shape needle Size/mm3 0.31×0.06×0.05 T/K 173(2) Crystal System monoclinic Space Group P21/c a/Å 5.6807(4) b/Å 17.3739(9) c/Å 26.0214(15) a/° 90 b/° 90.501(4) g/ ° 90 V/Å3 2568.1(3) Z 8 Z' 2 Wavelength/Å 1.541838 Radiation type CuKa Qmin/° 3.058 Qmax/° 72.329 Measured Refl. 26476 Independent Refl. 5018 Reflections with I > 2(I) 3962 Rint 0.0710 Parameters 325 Restraints 0 Largest Peak 0.460 Deepest Hole -0.581 GooF 1.049 wR2 (all data) 0.0855 wR2 0.0769 R1 (all data) 0.0502 R1 0.0337 79 Structure Quality Indicators Reflections: Refinement: A colourless needle-shaped crystal with dimensions 0.31×0.06×0.05 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a Bruker APEX-II CCD diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 173(2) K. Data were measured using w and f of 1.00° per frame for 75.00 s using CuKa radiation (sealed tube, 40 kV, 30 mA). The total number of runs and images was based on the strategy calculation from the program COSMO (BRUKER, V1.61, 2009). The actually achieved resolution was Q = 72.329. Cell parameters were retrieved using the SAINT (Bruker, V8.38A, after 2013) software and refined using SAINT (Bruker, V8.38A, after 2013) on 8310 reflections, 31 % of the observed reflections. Data reduction was performed using the SAINT (Bruker, V8.38A, after 2013) software which corrects for Lorentz polarization. The final completeness is 99.90 out to 72.329 in Q SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0930 before and 0.0607 after correction. The Ratio of minimum to maximum transmission is 0.7816. The l/2 correction factor is Not present. The structure was solved in the space group P21/c (# 14) by Intrinsic Phasing using the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program. The structure was refined by Least Squares using version 2014/6 of XL (Sheldrick, 2008) incorporated in Olex2 (Dolomanov et al., 2009). All non-hydrogen atoms were refined 80 anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model, except for the hydrogen atom on the non-carbon atom(s) which was found by difference Fourier methods and refined isotropically. The value of Z' is 2. This means that there are two independent molecules in the asymmetric unit. Figure I-23. X-ray structure of I-46a (different views) 81 I-6-7-2 Crystal data for I-46b Experimental. Single colourless needle-shaped crystals of I-46b were used as received. A suitable crystal 0.31×0.07×0.04 mm3 was selected and mounted on a nylon loop with paratone oil on a Bruker APEX-II CCD diffractometer. The crystal was kept at a steady T = 173(2) K during data collection. The structure was solved with the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program using the Intrinsic Phasing solution method and by using Olex2 (Dolomanov et al., 2009) as the graphical interface. The model was refined with version 2018/3 of ShelXL (Sheldrick, Acta Cryst. A64 2008, 112-122) using Least Squares minimization. Crystal Data. C14H15BrO3, Mr = 311.17, monoclinic, P21/n (No. 14), a = 21.3782(10) Å, b = 5.8155(3) Å, c = 21.6027(12) Å, b = 102.604(4)°, a = g = 90°, V = 2621.0(2) Å3, T = 173(2) K, Z = 8, Z' = 2, µ(CuKa) = 4.267, 19675 reflections measured, 4921 unique (Rint = 0.1967) which were used in all calculations. The final wR2 was 0.1496 (all data) and R1 was 0.0614 (I > 2(I)). 82 Compound I-46b CCDC 1942944 Formula C14H15BrO3 Dcalc./ g cm-3 1.577 µ/mm-1 4.267 Formula Weight 311.17 Color colourless Shape needle Size/mm3 0.31×0.07×0.04 T/K 173(2) Crystal System monoclinic Space Group P21/n a/Å 21.3782(10) b/Å 5.8155(3) c/Å 21.6027(12) a/° 90 b/° 102.604(4) g/ ° 90 V/Å3 2621.0(2) Z 8 Z' 2 Wavelength/Å 1.541838 Radiation type CuKa Qmin/° 2.634 Qmax/° 70.141 Measured Refl. 19675 Independent Refl. 4921 Reflections with I > 2(I) 2486 Rint 0.1967 Parameters 325 Restraints 0 Largest Peak 0.975 Deepest Hole -0.551 GooF 0.966 wR2 (all data) 0.1496 wR2 0.1189 R1 (all data) 0.1438 R1 0.0614 83 Structure Quality Indicators Reflections: Refinement: A colourless needle-shaped crystal with dimensions 0.31×0.07×0.04 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a Bruker APEX-II CCD diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 173(2) K. Data were measured using w and f of 1.00° per frame for 225.00 s using CuKa radiation (sealed tube, 40 kV, 30 mA). The total number of runs and images was based on the strategy calculation from the program COSMO (BRUKER, V1.61, 2009). The actually achieved resolution was Q = 70.141. Cell parameters were retrieved using the SAINT (Bruker, V8.38A, after 2013) software and refined using SAINT (Bruker, V8.38A, after 2013) on 1667 reflections, 8 % of the observed reflections. Data reduction was performed using the SAINT (Bruker, V8.38A, after 2013) software which corrects for Lorentz polarization. The final completeness is 99.40 out to 70.141 in Q SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0981 before and 0.0754 after correction. The Ratio of minimum to maximum transmission is 0.7378. The l/2 correction factor is Not present. The structure was solved in the space group P21/n (# 14) by Intrinsic Phasing using the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program. The structure was refined by Least Squares using version 2014/6 of XL (Sheldrick, 2008) incorporated in Olex2 (Dolomanov et al., 2009). All non-hydrogen atoms were refined 84 anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model, except for the hydrogen atom on the non-carbon atom(s) which was found by difference Fourier methods and refined isotropically. The value of Z' is 2. This means that there are two independent molecules in the asymmetric unit. Figure I-24. X-ray structure of I-46b (different views) 85 I-6-7-3 Crystal data for I-100 Experimental. Single colourless needle-shaped crystals of I-100 were used as received. A suitable crystal 0.40×0.07×0.05 mm3 was selected and mounted on a nylon loop with paratone oil on a Bruker APEX-II CCD diffractometer. The crystal was kept at a steady T = 173(2) K during data collection. The structure was solved with the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program using the Intrinsic Phasing solution method and by using Olex2 (Dolomanov et al., 2009) as the graphical interface. The model was refined with version 2018/3 of ShelXL (Sheldrick, Acta Cryst. A64 2008, 112-122) using Least Squares minimization. Crystal Data. C14H14Br2O3, Mr = 390.07, monoclinic, P21/c (No. 14), a = 9.4982(2) Å, b = 5.70550(10) Å, c = 26.4310(6) Å, b = 100.057(2)°, a = g = 90°, V = 1410.34(5) Å3, T = 173(2) K, Z = 4, Z' = 1, µ(CuKa) = 7.312, 7919 reflections measured, 2553 unique (Rint = 0.0546) which were used in all calculations. The final wR2 was 0.1059 (all data) and R1 was 0.0418 (I > 2(I)). 86 Compound I-100 CCDC 1942945 Formula C14H14Br2O3 Dcalc./ g cm-3 1.837 µ/mm-1 7.312 Formula Weight 390.07 Color colourless Shape needle Size/mm3 0.40×0.07×0.05 T/K 173(2) Crystal System monoclinic Space Group P21/c a/Å 9.4982(2) b/Å 5.70550(10) c/Å 26.4310(6) a/° 90 b/° 100.057(2) g/ ° 90 V/Å3 1410.34(5) Z 4 Z' 1 Wavelength/Å 1.541838 Radiation type CuKa Qmin/° 3.396 Qmax/° 70.108 Measured Refl. 7919 Independent Refl. 2553 Reflections with I > 2(I) 1940 Rint 0.0546 Parameters 172 Restraints 0 Largest Peak 0.917 Deepest Hole -0.634 GooF 1.002 wR2 (all data) 0.1059 wR2 0.0967 R1 (all data) 0.0623 R1 0.0418 87 Structure Quality Indicators Reflections: Refinement: A colourless needle-shaped crystal with dimensions 0.40×0.07×0.05 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a Bruker APEX-II CCD diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 173(2) K. Data were measured using w and f of 1.00° per frame for 100.00 s using CuKa radiation (sealed tube, 40 kV, 30 mA). The total number of runs and images was based on the strategy calculation from the program COSMO (BRUKER, V1.61, 2009). The actually achieved resolution was Q = 70.108. Cell parameters were retrieved using the SAINT (Bruker, V8.38A, after 2013) software and refined using SAINT (Bruker, V8.38A, after 2013) on 2647 reflections, 33 % of the observed reflections. Data reduction was performed using the SAINT (Bruker, V8.38A, after 2013) software which corrects for Lorentz polarization. The final completeness is 96.10 out to 70.108 in Q SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0771 before and 0.0537 after correction. The Ratio of minimum to maximum transmission is 0.7349. The l/2 correction factor is Not present. The structure was solved in the space group P21/c (# 14) by Intrinsic Phasing using the ShelXT (Sheldrick, G.M. (2015). Acta Cryst. A71, 3-8) structure solution program. The structure was refined by Least Squares using version 2014/6 of XL (Sheldrick, 2008) incorporated in Olex2 (Dolomanov et al., 2009). All non-hydrogen atoms were refined 88 anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model, except for the hydrogen atom on the non-carbon atom(s) which was found by difference Fourier methods and refined isotropically. There is a single molecule in the asymmetric unit, which is represented by the reported sum formula. In other words: Z is 4 and Z' is 1. Figure I-25. X-ray structure of I-100 (different views) 89 I-6-7-4 Crystal data for I-99a Experimental. Single colourless needle crystals of I-99a used as received. A suitable crystal with dimensions 0.31 × 0.04 × 0.02 mm3 was selected and mounted on a nylon loop with paratone oil on a XtaLAB Synergy, Dualflex, HyPix diffractometer. The crystal was kept at a steady T = 100.00(10) K during data collection. The structure was solved with the ShelXS (Sheldrick, 2008) solution program using direct methods and by using Olex2 (Dolomanov et al., 2009) as the graphical interface. The model was refined with ShelXL 2018/3 (Sheldrick, 2015) using full matrix least squares minimisation on F2. Crystal Data. C15H17BrO3, Mr = 325.20, orthorhombic, Pca21 (No. 29), a = 12.2672(5) Å, b = 6.3114(3) Å, c = 35.3845(15) Å, a = b = g = 90°, V = 2739.6(2) Å3, T = 100.00(10) K, Z = 8, Z' = 2, µ(Cu Ka) = 4.109, 13914 reflections measured, 4587 unique (Rint = 0.0678) which were used in all calculations. The final wR2 was 0.1874 (all data) and R1 was 0.0681 (I≥2 s(I)). 90 Compound I-99a Formula C15H17BrO3 CCDC 2036932 Dcalc./ g cm-3 1.577 µ/mm-1 4.109 Formula Weight 325.20 Colour colourless Shape needle Size/mm3 0.31×0.04×0.02 T/K 100.00(10) Crystal System orthorhombic Flack Parameter 0.03(5) Hooft Parameter 0.01(2) Space Group Pca21 a/Å 12.2672(5) b/Å 6.3114(3) c/Å 35.3845(15) a/° 90 b/° 90 g/ ° 90 V/Å3 2739.6(2) Z 8 Z' 2 Wavelength/Å 1.54184 Radiation type Cu Ka Qmin/° 2.497 Qmax/° 77.860 Measured Refl's. 13914 Indep't Refl's 4587 Refl's I≥2 s(I) 4177 Rint 0.0678 Parameters 343 Restraints 1 Largest Peak 0.824 Deepest Hole -0.822 GooF 1.077 wR2 (all data) 0.1874 wR2 0.1832 R1 (all data) 0.0723 R1 0.0681 91 Structure Quality Indicators Reflections: Refinement: A colourless needle-shaped crystal with dimensions 0.31×0.04×0.02 mm3 was mounted on a nylon loop with paratone oil. Data were collected using a XtaLAB Synergy, Dualflex, HyPix diffractometer equipped with an Oxford Cryosystems low-temperature device, operating at T = 100.00(10) K. Data were measured using w scans of 0.5° per frame for 3.5/14.0 s using Cu Ka radiation (micro-focus sealed X-ray tube, 50 kV, 1 mA). The total number of runs and images was based on the strategy calculation from the program CrysAlisPro (Rigaku, V1.171.40.84a, 2020). The actually achieved resolution was Q = 77.860. Cell parameters were retrieved using the CrysAlisPro (Rigaku, V1.171.40.84a, 2020) software and refined using CrysAlisPro (Rigaku, V1.171.40.84a, 2020) on 5380 reflections, 39 % of the observed reflections. Data reduction was performed using the CrysAlisPro (Rigaku, V1.171.40.84a, 2020) software which corrects for Lorentz polarization. The final completeness is 99.80 out to 77.860 in Q CrysAlisPro 1.171.40.84a (Rigaku Oxford Diffraction, 2020) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. The structure was solved in the space group Pca21 (# 29) by using direct methods using the ShelXS (Sheldrick, 2008) structure solution program. The structure was refined by Least Squares using version 2018/2 of XL (Sheldrick, 2008) incorporated in Olex2 (Dolomanov et al., 2009). All non-hydrogen atoms were refined anisotropically. Hydrogen 92 atom positions were calculated geometrically and refined using the riding model, except for the hydrogen atom on the non-carbon atom(s) which were found by difference Fourier methods and refined isotropically when data permits. The value of Z' is 2. This means that there are two independent molecules in the asymmetric unit. The Flack parameter was refined to 0.03(5). Determination of absolute structure using Bayesian statistics on Bijvoet differences using the Olex2 results in 0.01(2). Note: The Flack parameter is used to determine chirality of the crystal studied, the value should be near 0, a value of 1 means that the stereochemistry is wrong and the model should be inverted. A value of 0.5 means that the crystal consists of a racemic mixture of the two enantiomers. 93 Figure I-26. X-ray structure of I-99a (different views) 94 REFERENCES (1) Oh, H.; Gloer, J. B.; Shearer, C. A. Massarinolins A-C: New bioactive sesquiterpenoids from the aquatic fungus Massarina tunicata. J Nat Prod 1999, 62 (3), 497-501. DOI: DOI 10.1021/np980447+. (2) Xiao, W. L.; Zhu, H. J.; Shen, Y. H.; Li, R. T.; Li, S. H.; Sun, H. D.; Zheng, Y. T.; Wang, R. R.; Lu, Y.; Wang, C.; et al. Lancifodilactone G: A unique nortriterpenoid isolated from Schisandra lancifolia and its anti-HIV activity. Org Lett 2005, 7 (11), 2145-2148. DOI: 10.1021/ol050502n. (3) Fan, Y. Y.; Zhang, H.; Zhou, Y.; Liu, H. B.; Tang, W.; Zhou, B.; Zuo, J. P.; Yue, J. M. Phainanoids A-F, A New Class of Potent Immunosuppressive Triterpenoids with an Unprecedented Carbon Skeleton from Phyllanthus hainanensis. J Am Chem Soc 2015, 137 (1), 138-141. DOI: 10.1021/ja511813g. (4) Brimble, M. A.; Robinson, S. G. Synthesis of tricyclic aryl spiroacetals related to the papulacandins. Tetrahedron 1996, 52 (28), 9553-9562. DOI: Doi 10.1016/0040-4020(96)00492-9. (5) Davis, D. C.; Walker, K. L.; Hu, C. H.; Zare, R. N.; Waymouth, R. M.; Dai, M. J. Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols. J Am Chem Soc 2016, 138 (33), 10693-10699. DOI: 10.1021/jacs.6b06573. (6) Fukuda, H.; Takeda, M.; Sato, Y.; Mitsunobu, O. Convenient Method for the Formation of 2-Oxo-1,6-Dioxaspiroalkene Rings. Synthesis-Stuttgart 1979, (5), 368-370. (7) Kambale, D. A.; Thorat, S. S.; Pratapure, M. S.; Gonnade, R. G.; Kontham, R. Lewis acid catalyzed cascade annulation of alkynols with alpha-ketoesters: a facile access to gamma-spiroketal-gamma-lactones. Chem Commun 2017, 53 (49), 6641-6644. DOI: 10.1039/c7cc03668j. (8) Yamamoto, M.; Yoshitake, M.; Yamada, K. Cyclization of Alkynecarboxylic Acids - a Route to an Oxaspirolactone. J Chem Soc Chem Comm 1983, (18), 991-992. DOI: DOI 10.1039/c39830000991. (9) Thorat, S. S.; Kontham, R. Recent advances in the synthesis of oxaspirolactones and their application in the total synthesis of related natural products. Org Biomol Chem 2019, 17 (31), 7270-7292. DOI: 10.1039/c9ob01212e. (10) Haruki, F. M. T. Y. S. O. M. A Convenient Method for the Formation of 2-Oxo-1,6- dioxaspiroalkene Rings. Synthesis 1979, 5, 368-370. DOI: 10.1055/s-1979-28684. 95 (11) Yoshida, J.; Sakaguchi, K.; Isoe, S. Oxidative [3+2] Cycloaddition of 1,3-Diketone and Olefin Using Electroorganic Chemistry. Tetrahedron Lett 1986, 27 (50), 6075- 6078. DOI: Doi 10.1016/S0040-4039(00)85402-7. (12) Gore, V. G.; Chordia, M. D.; Narasimhan, N. S. Improved Syntheses of Shihunine, the Spiro Phthalide Pyrrolidine Alkaloid. Tetrahedron 1990, 46 (7), 2483-2494. (13) Cala, L.; Mendoza, A.; Fananas, F. J.; Rodriguez, F. A catalytic multicomponent coupling reaction for the enantioselective synthesis of spiroacetals. Chem Commun 2013, 49 (26), 2715-2717. DOI: 10.1039/c3cc00118k. (14) heng, T. W., X.; Ng, W.-H.; Tse, Y.-L. S.; Yeung, Y.-Y. . Catalytic enantio- and diastereoselective domino halocyclization and spiroketalization. Nature Catalysis 2020, 3, 993-1001. (15) Whitehead, D. C.; Yousefi, R.; Jaganathan, A.; Borhan, B. An Organocatalytic Asymmetric Chlorolactonization. J Am Chem Soc 2010, 132 (10), 3298-+. DOI: 10.1021/ja100502f. (16) Jaganathan, A.; Garzan, A.; Whitehead, D. C.; Staples, R. J.; Borhan, B. A Catalytic Asymmetric Chlorocyclization of Unsaturated Amides. Angew Chem Int Edit 2011, 50 (11), 2593-2596. DOI: 10.1002/anie.201006910. (17) Garzan, A.; Jaganathan, A.; Marzijarani, N. S.; Yousefi, R.; Whitehead, D. C.; Jackson, J. E.; Borhan, B. Solvent-Dependent Enantiodivergence in the Chlorocyclization of Unsaturated Carbamates. Chem-Eur J 2013, 19 (27), 9015- 9021. DOI: 10.1002/chem.201300189. (18) Ashtekar, K. D.; Marzijarani, N. S.; Jaganathan, A.; Holmes, D.; Jackson, J. E.; Borhan, B. A New Tool To Guide Halofunctionalization Reactions: The Halenium Affinity (HalA) Scale. J Am Chem Soc 2014, 136 (38), 13355-13362. DOI: 10.1021/ja506889c. (19) Ashtekar, K. D.; Vetticatt, M.; Yousefi, R.; Jackson, J. E.; Borhan, B. Nucleophile- Assisted Alkene Activation: Olefins Alone Are Often Incompetent. J Am Chem Soc 2016, 138 (26), 8114-8119. DOI: 10.1021/jacs.6b02877. (20) Ashtekar, K. D.; Gholami, H.; Moemeni, M.; Chakraborty, A.; Kiiskila, L.; Ding, X. L.; Toma, E.; Rahn, C.; Borhan, B. A Mechanistically Inspired Halenium Ion Initiated Spiroketalization: Entry to Mono- and Dibromospiroketals. Angew Chem Int Edit 2022, 61 (8). DOI: ARTN e20211517310.1002/anie.202115173. (21) Kitching, W.; Lewis, J. A.; Fletcher, M. T.; Devoss, J. J.; Drew, R. A. I.; Moore, C. J. Spiroacetals from Dienones and Hydroxyenones by Mercury(Ii) Cyclization. J Chem Soc Chem Comm 1986, (11), 855-856. DOI: DOI 10.1039/c39860000855. 96 (22) Holson, E. B.; Roush, W. R. Diastereoselective synthesis of the C(17)-C(28) fragment (The C-D spiroketal unit) of spongistatin 1 (altohyrtin A) via a kinetically controlled iodo-spiroketalization reaction. Org Lett 2002, 4 (21), 3719-3722. DOI: 10.1021/ol0266875. (23) Commandeur, M.; Commandeur, C.; Cossy, J. Synthesis of a Platform To Access Bistramides and Their Analogues. Org Lett 2011, 13 (22), 6018-6021. DOI: 10.1021/ol202483u. (24) Zhou, L.; Tan, C. K.; Jiang, X. J.; Chen, F.; Yeung, Y. Y. Asymmetric Bromolactonization Using Amino-thiocarbamate Catalyst. J Am Chem Soc 2010, 132 (44), 15474-15476. DOI: 10.1021/ja1048972. (25) Zhou, L.; Tay, D. W.; Chen, J.; Leung, G. Y. C.; Yeung, Y. Y. Enantioselective synthesis of 2-substituted and 3-substituted piperidines through a bromoaminocyclization process. Chem Commun 2013, 49 (39), 4412-4414. DOI: 10.1039/c2cc36578b. (26) Resek, J. E. Intramolecular Ene Reaction of a Chiral Bicyclic Lactam. J Org Chem 2008, 73 (24), 9792-9794. DOI: 10.1021/jo801696r. (27) Braddock, D. C.; Millan, D. S.; Perez-Fuertes, Y.; Pouwer, R. H.; Sheppard, R. N.; Solanki, S.; White, A. J. P. Bromonium Ion Induced Transannular Oxonium Ion Formation-Fragmentation in Model Obtusallene Systems and Structural Reassignment of Obtusallenes V-VII. J Org Chem 2009, 74 (5), 1835-1841. DOI: 10.1021/jo8026577. (28) Guella, G.; Mancinci, I.; Oztunc, A.; Pietra, F. Conformational bias in macrocyclic ethers and observation of high solvolytic reactivity at a masked furfuryl (=2- furylmethyl) C-atom. Helv Chim Acta 2000, 83 (2), 336-348. DOI: Doi 10.1002/(Sici)1522-2675(20000216)83:2<336::Aid-Hlca336>3.0.Co;2-R. (29) Uenishi, J.; Fujikura, Y.; Kawai, N. Pd-II-Catalyzed Cascade Reaction with 1,3- Chirality Transfer; Stereoselective Synthesis of Chiral Nonracemic 2,2 '-THF-THF Ring Units. Org Lett 2011, 13 (9), 2350-2353. DOI: 10.1021/ol2005984. (30) Sun, Z. K.; Winschel, G. A.; Borovika, A.; Nagorny, P. Chiral Phosphoric Acid- Catalyzed Enantioselective and Diastereoselective Spiroketalizations. J Am Chem Soc 2012, 134 (19), 8074-8077. DOI: 10.1021/ja302704m. (31) Shimizu, T.; Murakoshi, K.; Yasui, K.; Sodeoka, M. A New Route for the Preparation of Succinates. Synthesis-Stuttgart 2008, (20), 3209-3218. DOI: 10.1055/s-0028-1083140. 97 (32) Orsini, F.; Pelizzoni, F. Pd(0)-Mediated Cross-Coupling of Reformatsky Reagents with Vinyl Triflates and Aryl Triflates. Synthetic Commun 1987, 17 (12), 1389-1402. DOI: Doi 10.1080/00397918708057763. (33) Sun, W.; Yuan, Y.; Lee, B.; Jun, H. S.; Shin, D.; Seo, S. Y. Short Synthesis of the Antidiabetic Octaketide Ethyl 2-(2,3,4-Trimethoxy-6-octanoylphenyl) acetate. Synlett 2018, 29 (3), 326-329. DOI: 10.1055/s-0036-1592062. (34) Wong, B.; Xin, L. H.; Crawford, J. J.; Drobnick, J.; Lee, W.; Zhang, H. M. A chemoselective Reformatsky-Negishi approach to alpha-haloaryl esters. Tetrahedron 2014, 70 (7), 1508-1515. DOI: 10.1016/j.tet.2013.12.053. (35) Chou, S. S. P.; Yang, K. S.; Chin, T. H. Synthesis of the Precursors of Pumiliotoxin 251d and Awajanomycin and Related Studies. Heterocycles 2014, 89 (3), 679- 691. DOI: 10.3987/Com-14-12930. (36) Tunge, J. A.; Mellegaard, S. R. Selective selenocatalytic allylic chlorination. Org Lett 2004, 6 (8), 1205-1207. DOI: 10.1021/ol036525o. (37) Vilsmaier, E.; Adam, R.; Tetzlaff, C.; Cronauer, R. Functionalized Chloroenamines in Aminocyclopropane Synthesis .3. Synthesis and Assignment of Configuration of 2 Isomeric Morpholinobicyclo[3.1.0]Hexane Derivatives. Tetrahedron 1989, 45 (12), 3683-3694. DOI: Doi 10.1016/S0040-4020(01)89230-9. (38) Mcdonald, R. N.; Davis, G. E. Strained Ring Systems .8. An Alternate Synthesis of 2-Oxy Derivatives of Bicyclo[2.2.O]Hexane and Rearrangement of Endo- Bicyclo[2.2.O]Hex-2-Yl Acetate. J Org Chem 1969, 34 (6), 1916-&. DOI: DOI 10.1021/jo01258a086. (39) Mock, W. L. Orbital Symmetry Forbiddenness in a Suprafacial 1,6 Cycloelimination of Sulfur Dioxide. J Am Chem Soc 1970, 92 (12), 3807-&. DOI: DOI 10.1021/ja00715a055. (40) Uemura, S.; Onoe, A.; Okazaki, H.; Okano, M.; Ichikawa, K. Chlorination of 1,3- Cyclooctadienes and 1,5-Cyclooctadienes with Various Chlorinating Agents. B Chem Soc Jpn 1976, 49 (5), 1437-1438. DOI: DOI 10.1246/bcsj.49.1437. (41) Zhang, Y. A.; Yaw, N.; Snyder, S. A. General Synthetic Approach for the Laurencia Family of Natural Products Empowered by a Potentially Biomimetic Ring Expansion. J Am Chem Soc 2019, 141 (19), 7776-7788. DOI: 10.1021/jacs.9b01088. (42) Ishihara, J.; Shimada, Y.; Kanoh, N.; Takasugi, Y.; Fukuzawa, A.; Murai, A. Conversion of prelaureatin into laurallene, a bromo-allene compound, by enzymatic and chemical bromo-etherification reactions. Tetrahedron 1997, 53 (25), 8371-8382. DOI: Doi 10.1016/S0040-4020(97)00542-5. 98 (43) Chatupheeraphat, A.; Soorukram, D.; Kuhakarn, C.; Tuchinda, P.; Reutrakul, V.; Pakawatchai, C.; Saithong, S.; Pohmakotr, M. Synthesis of gem- Difluoromethylenated Spiro-gamma-butyrolactones by Employing PhSCF2Si(CH3)(3) as a gem-Difluoromethylenating Agent. Eur J Org Chem 2013, 2013 (30), 6844-6858. DOI: 10.1002/ejoc.201300998. (44) Wang, Y.; Milkiewicz, K. L.; Kaufman, M. L.; He, L. L.; Landmesser, N. G.; Levy, D. V.; Allwein, S. P.; Christie, M. A.; Olsen, M. A.; Neville, C. J.; et al. Plant Process for the Preparation of Cinchona Alkaloid-Based Thiourea Catalysts. Org Process Res Dev 2017, 21 (3), 408-413. DOI: 10.1021/acs.oprd.7b00049. 99 Chapter II: Design and Development of Organic Dyes for Transparent Luminescent Solar Concentrators (TLSCs) 100 II-1 Introduction of Transparent Luminescent Solar Concentrators (TLSCs) Mitigating the world’s growing global demand for energy remains a challenge, but harvesting solar energy is a key part of the solution to this problem. Many systems have been invented and developed with the aim of harvesting this sustainable energy source by converting the suns solar spectrum into electric power.1 In the last decade, solar cells have been installed in mass numbers on rural farmlands or building rooftops. Other potential options to absorb the sun’s light, still unutilized, are the vast amounts of building surfaces in urban and dense high-rise areas.2 Therefore, fabrication of light harvesting devices on window surfaces remains a highly desired target for solar harvesting. Low cost and flexible Transparent Luminescent Solar Concentrators (LSCs) dispersed within glass in the windows have attracted much attention due to their potential to convert a building into an efficient power generating source via solar to current conversion.3-6 PV Figure II-1. A. TLSC model in which both UV and NIR light is absorbed while visible light passes through. B. Spectra of chromophore; S stand for Stokes shift, W is the width of the emission peak (Permission to reproduce this figure is kindly provided by Prof. Lunt and Dr. Yang)7 101 Transparent luminescent solar concentrators selectively convert non-visible light, such as UV light and Near-infrared (NIR) light, into electricity while the vast majority of visible light would pass through, which translates to a high level of visible transparency. As such, a vital design parameter is to minimize the chromophore’s absorption and emission in the range of 400 nm to 700 nm (visible wavelength). Working principle of TLSC is to employ the chromophoric materials within the window to absorb the UV or/and NIR light, and re-emit the light to the edge of the window (by total internal reflection) that is lined with photovoltaics (PV) (Figure II-1). This project is a collaboration with professor Richard Lunt’s group (Chemical Engineering Department, Michigan State University) which pioneered this work. Our group has previously and currently engineered and synthesized light harvesting organic dyes and studied their application in transparent luminescent solar concentrators. II-2 Important parameters for investigating TLSC devices The key parameter to compare the performance of various solar cells is the power conversion efficiency (PCE), which is the ratio of maximum output energy density (Pmax.out) to the sun light’s energy input density (P0) . In order to quantify the PCE of TLSC devices, we need to address three important parameters, all of which can be extracted through the corresponding current density (J) - voltage (V) curve. The first is the short-circuit current density (JSC), which defines the current (ISC) value at zero voltage bias (V = 0) divided by A, which is the active area of the solar cell (JSC = ISC/A). The second is VOC, which is the voltage at open-circuit condition (I = 0). The third parameter we need is the fill factor (FF), 102 this represents the “squareness” of the J-V curve (see Figure II-2A for an example of a J- V curve for two different solar cell). 𝑃!"#,%&' 𝑉)* ∙ 𝐽+* ∙ 𝐹𝐹 𝑃𝐶𝐸 = = (2.1) 𝑃( 𝑃( The other important parameters for the characterization of solar cells are the external quantum efficiency (EQEPV) and the internal quantum efficiency (IQEPV). The EQEPV is the ratio of the number of photogenerated electrons collected at the solar cell to the number of photons which shine on the device at each wavelength. The IQEPV is the ratio of the number of photogenerated electrons collected at the solar cell to the number of photons which shine on the device and are absorbed at each wavelength. electrons⁄𝑠𝑒𝑐 𝐸𝑄𝐸,- = (2.2) 𝑝ℎ𝑜𝑡𝑜𝑛𝑠⁄𝑠𝑒𝑐 electrons⁄𝑠𝑒𝑐 𝐼𝑄𝐸,- = (2.3) 𝑎𝑏𝑠𝑜𝑟𝑏𝑒𝑑 𝑝ℎ𝑜𝑡𝑜𝑛𝑠⁄𝑠𝑒𝑐 The EQEPV is related to IQEPV according to below equation: 𝐸𝑄𝐸,- (𝜆) = 𝜂./0 (𝜆) ∙ 𝐼𝑄𝐸,- (𝜆) (2.4) which ηAbs is the photovoltaic absorption efficiency at each wavelength. (see Figure II-2B for EQEPV spectra of a silicon and a Gallium Arsenide (GaAs) photovoltaic cells) . 103 A B Figure II-2 A. Examples of J-V curves for two different solar cells. B. External quantum efficiency spectra of a silicon and GaAs PV cells (Permission to reproduce this figure is kindly provided by Prof. Lunt and Dr. Yang)7 The main parameter utilized to study the transparency performance of a solar cell is coined as the average visible transmission (AVT) which defines the percentage of visible light that passes through the device. The combination of PCE and AVT which together is called Light Utilization Efficiency (LUE = PCE × AVT), defines the last factor for evaluation of transparent photovoltaic devices.7 II-3 Development of organic dyes for use with TLSC devices II-3-1 General strategy for tuning the Stokes shift of cyanine dyes In a TLSC, the organic chromophores should absorb sun light selectively in UV or NIR region, while maintaining minimal visible transmission, in order to generate a transparent solar concentrator. Lunt’s group has successfully studied highly efficient nanoclusters for harvesting light in the UV region.8, 9 In this chapter we mainly focus on the NIR portion of the spectrum. We explored various NIR fluorophores after which we turned to heptamethine cyanine dyes. These dyes have the potential to be excellent 104 candidates for harvesting the NIR light, due to their high quantum yield (QY), brightness and their narrow emission profile in a region that is devoid of many spectral interferences.10-12 However, most cyanine dyes exhibit a small Stokes shift, which negatively impacts their application in optical imaging due to significant background, light scattering and internal absorbance interferences. We also found that there is a direct relationship between the dye’s Stokes shift and the corresponding TLSC device’s efficiency. As illustrated in Figure II-3, the calculated optical efficiency as a function of LSC device length has a direct correlation with the Stokes shift of the organic dyes and as such, implementation of materials possessing a small Stokes shift would lead to lower system efficiency.7,13, 14 This effect of Stokes shift on the optical efficiency is higher with increasing the length of the device (Figure II-3). Figure II-3. LSC system as a function of calculated Stokes shift (Permission to reproduce this figure is kindly provided by Prof. Lunt and Dr. Yang)7 105 The primary factor in efficiency loss, stems from the self-quenching process of small Stokes shift organic dyes installed on the device. With the maximum absorption and emission overlap (see Figure II-4a), the emission of one dye is reabsorbed by another proximal dye which hinders the photon output to PV material located in the window’s edge. Increasing the Stokes shift would decrease this spectral overlap region resulting in diminished self-quenching (Figure II-4b). With this knowledge in hand, we aim to develop a general strategy to tune the Stokes shift of heptamethine cyanine dyes. Figure II-4. Correlation of Stokes shift and self-quenching In 2005, the Peng group reported the first large Stokes shift heptamethine cyanines.15 Nucleophilic addition/elimination of the meso chloro group at the C4 position of Cy7 (II-1) by simple primary amines resulted in a massive Stokes shift. As is shown in Table II-1, the cyclohexanemethylamine II-2 and benzyl amine lI-3 yield a Stokes shift of 150 nm and 140 nm, respectively. With limited mechanistic understanding for this observation it was suggested that a change of the amine’s pyramidal geometry in the excited state leads to the observed increase in Stokes shift. 106 Table II-1. Strategy to achieve large Stokes shift cyanine dyes O3S SO3H O3S SO3H RNH2 Cl NHR DMF N N N N Bn Bn Bn Bn II-1 II-2 Dye NHR lmax (nm)a lem (nm)a Stokes Shift (nm) Φ (%)a II-1 --- 783 803 20 17 II-2 H 602 757 155 47 N H N II-3 617 757 140 38 [a] Absorption, emission and absolute quantum yield data were obtained in methanol. Other seminal work by the Maury group studied the effect of various substitutions at the C4 position of multiple polymethine dyes, leading to the development of a new bis- dipole structure for cyanine dyes.16 As shown in Figure II-5, the absorption properties of a cyanine would be affected by electronic character of its C4-substituent. It was observed that groups such as halogens or thioethers exhibit absorption profiles similar to general cyanines, while strong electron donating groups like ketone (hydroxyl) or imines (amines) could break the cyanine’s conjugation with its heterocyclic ends, blue shifting the absorption by generation of a bis-dipole type structure. However, the impact of these substituents on the Stokes shift was not investigated in this work. 107 Y N N Bn Bn Y Y Y D D D D D D Y= C(CN)2 Y= NH R= NO2 Y= Cl O CF3 Br NPh H SPh NPr OMe OAc R OPh NEt2 H NC5H10 NHPr Y Y Y D D D D D D Y electron- donating strength λabs Bis-dipole Cyanine Figure II-5. Bis-dipole structure of substituted cyanines As mentioned above, prior work aimed at increasing the Stokes shifts of cyanine dyes have explored primary amine substitutions, geometrically twisted structures, and novel donor groups. Nonetheless, these methods have not offered a reliable strategy for tuning or rational means of predicting the Stokes shift. A variety of cyclic and acyclic amine substituents were screened in the prior study. In our work, we have expanded the structural variations of the substituents (a variety of cyclic and acyclic amine substituents) as well as the cyanine backbone, in order to comprehend the underlying principles that 108 affect the spectroscopic characteristics, and in particular, the Stokes shift. In doing so, we have identified a simple strategy to tune the Stokes shift of heptamethine cyanine dyes by tuning the relative energies of conformers of the dye differentiated by rotation about the central amine group. A conventional heptamethine cyanine dye II-6 was chosen to investigate the effects of different nitrogen substituents on the observed Stokes shift. The general synthesis of different heptamethine cyanine backbones is shown in Figure II-6.17 O Cl N POCl3, DMF I OHC Cl OH AcONa, Ac2O N N I II-4 II-5 II-6 S Cl S Cl N N N N I I II-8 II-7 Figure II-6. Synthesis of heptamethine cyanine dyes Two categories of cyanine dyes (substituted with acyclic and cyclic amines) were synthesized via addition–elimination, promoted by diisopropylethylamine (DIPEA) and excess amine in acetonitrile (Figure II-7). Acyclic amine substituted cyanine dyes include dimethyl amino (II-10), methyl ethyl amino (II-11) and diethyl amino groups (II-12), whereas heterocyclic groups include methyl aziridine (II-13), azetidine (II-14), pyrrolidine (II-15) and piperidine (II-16). 109 R1 R2 N R1 R2 Cl H N N N DIPEA, ACN N N I 70 ºC I II-6 II-9 Series A N N N N N N I I II-10 II-11 N N N N N N I I II-13 II-12 N N N N N N I I II-14 II-15 N N N I II-16 Figure II-7. Synthesis of first series of amine substituted heptamethine cyanine dyes Attempts to synthesize the seven membered azepane substituted cyanine were not fruitful, as the product could not be isolated in its pure form. Table II-2 summarizes spectroscopic properties for dyes II-9 to II-16. 110 Table II-2. Spectroscopic data of amine substituted heptamethine cyanines Dye NR2 lmax (nm)a lem (nm)a Stokes Shift (nm) FWHM (nm) Φ (%)b II-6 - 785 806 21 - 15 II-10 N 664 777 113 117 28 II-11 N 684 778 94 110 29 II-12 742 766 24 94 25 N II-13 615 704 89 80 26 N II-14 N 699 778 79 98 31 II-15 604 784 180 85 33 N II-16 668 785 117 133 23 N FWHM, full width at half maximum; lmax, absorption maximum; lem, emission maximum; φ, quantum yield. [a] Absorptions and emissions were recorded in DCM at rt; [b] Absolute quantum yields were measured by Hamamatsu Quantaurus fluorimeter in DCM at rt. Cyanine dye II-6 exhibits an absorption maximum in the NIR region (lmax = 785 nm), emission maximum (lem = 806 nm), with a small Stokes shift (21 nm) in DCM. To our surprise, while dyes II-10 and II-12 share a similar structure, they are quite different spectroscopically (Figure II-8 top). Dye II-10 absorbs at 664 nm and emits at 777 nm in DCM, leading to a 113 nm Stokes shift. In contrast, aziridinyl substrate dye II-12 shows a 24 nm Stokes shift. Interestingly, the quantum yield is not improved by using aziridinyl or azetidinyl rings (25% for dye II-12 and 26% for dye II-3). 111 N N N N N N I I II-10 II-12 1 1 Abs/Em (normalized) Abs/Em (normalized) 0 0 400 500 600 700 800 900 400 500 600 700 800 900 Wavelength (nm) Wavelength (nm) N N N N N N I I II-14 II-15 1 1 Abs/Em (normalized) Abs/Em (normalized) 0 0 400 500 600 700 800 900 400 500 600 700 800 900 Wavelength (nm) Wavelength (nm) Figure II-8. Normalized absorption and fluorescence emission spectra (measured in DCM) for dyes II-10 (top left) and II-12 (top right), and dyes II-14 (bottom left) and II-15 (bottom right) In contrast, the opposite trend is observed for dyes II-14 and II-15 (Figure II-8 bottom). Diethylamine substrate II-14 yields a moderate 79 nm Stokes shift (absorption at 699 nm and emission at 778 nm), while the cyclic pyrrolidine substituted cyanine 7 112 leads to an even larger Stokes shift (180 nm). Notably, the quantum yields are similar (31% for dye II-14 and 33% for dye II-15). These observations indicate that the Stokes shift of cyanine dyes can be easily tuned by varying the amine substituents ranging from 24 nm up to 180 nm. Based on the collective data obtained, some trends can be observed amongst the series. Cyclic and acyclic amines appear to behave differently; the smaller acyclic amines lead to a larger Stokes shifts, while smaller cyclic amines yield a smaller Stokes shift. Another notable observation is that most of these dyes (except dye II-13) share similar emission profiles (around 770 nm). The change in Stokes shift is dictated mainly by the blueshift of the absorption. Thus, we speculated that these dyes may have different ground state geometries. It is notable that the azetidine substituted dye II-13 possesses strong solvatochromic properties in various solvents. The photophysical properties of dye II-13 in different solvents are reported in Table II-3. Table II-3. Spectroscopic data of dye II-13 in different solvents Solvent lmax (nm)a lem (nm)a Stokes Shift (nm) DCM 615 704 89 Methanol 589 701 112 Acetone 585 704 119 Toluene 574 679 105 lmax, absorption maximum; lem, emission maximum. 113 To examine the generality of the trend described above, similar amine substitutions were made with other series of cyanine dyes. The second series that was synthesized contained indocyanine green (ICG) as the head group (Figure II-9). Series B N N N N N N I I II-17 II-18 N N N N N N I I II-20 II-19 N N N N N N I I II-21 II-22 N N N I II-23 Figure II-9. Structure of second series of amine substituted heptamethine cyanine dyes Photophysical characteristics of these dyes are listed in Table II-4. In comparison to cyanine dyes II-10 – II-16 in Table II-3, ICG type dyes II-17 – II-23 possess a larger 114 conjugated aryl ring, and are red shifted by around 40 nm, while maintaining the same Stokes shift trend. The largest Stokes shift was seen with dye II-22 containing the pyrrolidine ring substitution (187 nm), while the smallest Stokes shift was the aziridinyl functionalized dye II-19 (56 nm). Table II-4. Spectroscopic data of amine substituted ICG based cyanine dyes Dye NR2 lmax (nm)a lem (nm)a Stokes Shift (nm) FWHM (nm) Φ (%)b II-17 N 705 818 113 124 24 II-18 N 724 816 92 116 26 II-19 746 802 56 128 24 N II-20 649 737 88 84 30 N II-21 N 739 819 80 107 24 II-22 636 823 187 85 25 N II-23 708 824 116 143 21 N FWHM, full width at half maximum; lmax, absorption maximum; lem, emission maximum; φ, quantum yield. [a] Absorptions and emissions were recorded in DCM at rt; [b] Absolute quantum yields were measured by Hamamatsu Quantaurus fluorimeter in DCM at rt. Most of the dyes listed in Table II-4 have a slightly lower quantum yield than their analogs in Table II-3, with the azetidine substituted dye II-20 having a slightly higher quantum yield (30%). In continuation of this study, we also synthesized benzothiazole based cyanine dyes and chose 3 representative substituents: dimethyl, diethyl, and pyrrolidinyl groups to examine their photophysical properties (Table II-5). Gratifyingly, the 115 same trend was also observed in these dyes featuring a large Stokes shift with pyrrolidinyl (171 nm for dye II-26) and a moderate Stokes shift with diethyl (69 nm for dye II-25). Table II-5. Structure and spectroscopic data of amine substituted benzothiazole based cyanines N N N N N N I I II-24 II-25 N N N I II-26 Dye NR2 lmax (nm)a lem (nm)a Stokes Shift (nm) FWHM (nm) Φ (%)b II-24 N 703 801 98 123 26 II-25 N 733 802 69 129 27 II-26 636 807 171 105 35 N FWHM, full width at half maximum; lmax, absorption maximum; lem, emission maximum; φ, quantum yield. [a] Absorptions and emissions were recorded in DCM at rt; [b] Absolute quantum yields were measured by Hamamatsu Quantaurus fluorimeter in DCM at rt. To investigate the mechanism underlying the observed change in the Stokes shift we carried a computational study of dyes II-10 – II-16. Calculating the spectroscopic properties of cyanine dyes remains challenging. For example, commonly used time- dependent density functional theory (TD-DFT) functionals cannot provide accurate transition energies for cyanine dyes, overestimating excitation energies by 0.5 – 1.0 eV. 116 Nonetheless, TD-DFT is established to provide an accurate description of the shape of the excited potential energy surfaces of these molecules.18, 19 Thus, one can expect TD- DFT to provide an accurate description of the Stokes shift and the associated displacement coordinate, with the caveat that it does not provide quantitative predictions of the excitations energies themselves. Before turning our attention to the excited state, we examined the ground state conformer. Geometry optimizations at the CAM-B3LYP/6-31G* level20 (performed with the TeraChem software package21, 22 show the s-trans conformer having a lower energy than the s-cis structure (differentiate by flipping of the indolium ring) for all dyes in the series II-9 to II-16. Interestingly, all seven of the amine-substituted dyes II-10 to II-16 have two distinct s-trans ground state minimum structures that differ in the rotation angle of the amine group (Figure II-10). In one minimum, the amine is rotated to be roughly in plane with the heptamethine chain, which we refer to as the parallel conformer. In the other structure, referred to as the perpendicular conformer, the amine is rotated approximately 90° with respect to the heptamethine chain. Structures for all optimized systems can be found in experimental section. The existence of two conformers is closely related to the concept elaborated upon in an elegant work by Guennic, Andraud, Maury and coworkers.16 Their conformational approach was used to determine the spectroscopic properties of substituted cyanine dyes: the distinction between bis-dipolar and cyanine-like electronic structures (Figure II- 10). A bis-dipolar system is characterized by alternating double and single bond character, which would occur when an amine nitrogen conjugates to the π system of the 117 chain (Figure II-10, left). In a cyanine-like system, bond orders of all carbon-carbon bonds in the heptamethine chain are roughly 1.5 (Figure II-10, right). The excitation energy, or extent of absorption blue shifting, tends to increase with increasing bis-dipolar character. R1 R2 N N N X R1 R2 R1 R2 N N N N N N X X Bis-dipolar Cyanine-like continuum of the bis-dipolar mode change in nitrogen N N atom pyramidalization bis-dipolar cyanine-like like ground state like ground state (blue-shifted) (red-shifted) Figure II-10. Generalized cyanine-like and bis-dipolar structures of cyanine dyes It is important to note that all perpendicular structures will exhibit cyanine-like character, because twisting about the amine bond breaks conjugation with the chain. Parallel structures, however, may exhibit a continuum of electronic character, from more bis-dipolar to more cyanine-like character, depending on the degree of π electron donation from the amine to the chain (see dashed box, Figure II-10). Interestingly, several of the amine-substituted dyes (II-10, II-11, II-14 and II-16) favor a perpendicular conformation, while the minority (II-12 and II-13) favor a parallel 118 conformation. Only those dyes with relatively narrow amine substituents (II-12 and II-13) favor the parallel conformation. Analysis of the C–C distance between the carbon atoms in the amine substituent and those in the polymethine chain suggests that steric interaction between these groups determines the ground state conformation. The parallel conformers of II-10, II-11, II-14 and II-16 all have C–C contacts between the amine substituent and the polymethine chain in the range 2.91–2.93 Å. These close contacts suggest that the parallel conformers of these dyes are sterically destabilized. On the other hand, the parallel conformers of II-12 and II-13 have no contacts shorter than 3.00 Å, and therefore are not sterically destabilized. For II-15, the calculations predict the difference in energy to be <1.5 kcal/mol, which is effectively equal, given the margin of error for this DFT approach. In this case, the closest C–C contact between the amine substituent and the polymethine chain is 2.94 Å, which is between the two extremes. For molecules with a clear lowest energy conformer (II-10 – II-14 and II-16), computing a Stokes shift is more straightforward. In each of these cases, two excited state minima (parallel and perpendicular) were optimized at the TD-CAM-B3LYP/6-31G* level, and in all cases the energetically favored conformer was the same as in the ground state. Figure II-11 is a scatter plot with the computed excitation energies on the x-axis and the experimentally measured spectral maxima on the y-axis. Blue marks indicate the experimental absorption maxima as a function of the computed vertical excitation energies from the ground state minimum structure. Red marks indicate the experimental emission maxima as a function of the computed vertical excitation energy at the excited state minimum structure. 119 II-15⟂ II-15∥ N II-15∥ (parallel) N II-15∥ II-15⟂ II-15⟂ (perpendicular) Figure II-11. Scatter plot of the experimental spectral energy maxima as a function of the DFT-computed theoretical excitation energies. Absorption and emission energies are shown by blue and red dots, respectively. The lowest energy conformer is chosen for II- 9 – II-14 and II-16, while for II-15, both the parallel (II-15∥) and perpendicular (II-15⟂) conformers are shown Though DFT consistently overestimates the experimental energies by 0.6 – 0.7 eV, a compelling pseudo linear relationship between experiment and theory is observed for molecules II-10 – II-12, II-14 and II-16. This suggests that the basic physics underlying the Stokes shift is well described. As will be discussed below, molecules II-13 and II-15 do not follow the trends due to other factors. As shown in Figure II-12, the experimental excitation energies correlate strongly with displacement along a bond length alternation coordinate (BLA) as determined from the calculated structures, supporting the 120 assignment of variances in the excitation energies to a shift between cyanine-like and bis- dipolar electronic character. Figure II-12. Scatter plot of the experimental spectral energy maxima as a function of the DFT-optimized bond length alternation coordinate (in angstrom). Absorption and emission energies are shown by blue and red dots, respectively Applying the same analysis to II-15, the molecule with the largest Stokes shift does not result in good agreement with experimental data (see Figure II-8). The fit is poor regardless of whether the perpendicular (II-15⟂) or parallel (II-15∥) conformer is chosen. In the parallel case, the absorption point falls on the line, but the emission point does not. On the other hand, in the perpendicular case, the emission point falls on the line, but the absorption point does not. This suggests the intriguing possibility that the molecule converts from the parallel to the perpendicular conformation upon excitation. A shift from 121 a strongly bis-dipolar character in the ground state to more cyanine-like character in the excited state is indicated by a reduction in BLA from 0.089 Å (the largest of all dyes studied here) to 0.034 Å. Such a reorganization mechanism has previously been recognized, but here we demonstrate the delicate energy balance that determines whether such rotation occurs or not.16, 23 As noted above, all perpendicular structures exhibit cyanine-like electronic structure. This includes both ground and excited states structures for II-10, II-11, II-14 and II-16 as well as the excited state structure for II-15. To determine the nature of the electronic structure of the parallel structures (both ground and excited states structures of II-12 and II-13, and the ground state structure of II-15), we must consider additional coordinates. Table II-6 presents the computed BLA displacement and pyramidalization angle about the amine nitrogen atom of these five structures (A Table containing these parameters for all structures can be found in the experimental section, along with explicit definitions of the BLA and pyramidalization angle coordinates). The computed ground state pyramidalization angles increase as the amine ring become more constrained, with dyes II-15, II-13, and II-12 having angles of 2.1°, 7.2°, and 43.4°, respectively. This change in hybridization from a nearly planar sp2 conformation in II-15 to a more sp3 conformation in II-12 results in decreased coupling of the amine lone pair to the π system of the heptamethine chain (see dashed box, Figure II-10). The reduction in the bis-dipolar character is evidenced by a decrease in the computed BLA (respectively 0.069, 0.057, and 0.036 Å) and increasing experimental λmax (respectively 604, 615, and 742 nm). A similar trend is seen in the excited state structures, with II-13 being the dye with more bis- 122 dipolar character upon excitation (BLA of 0.044 Å) and a correspondingly high emission energy (λem = 704 nm). Table II-6. Important geometric parameters that determine the electronic character (bis- dipolar vs. cyanine-like) of the five structures in the parallel conformationa Dye NR2 Stateb BLA (Å) Pyr. Ang. (°) GS 0.036 43.3 II-12 N ES 0.023 49.4 GS 0.057 7.2 II-13 N ES 0.044 15.9 II-15 GSc 0.069 2.1 N BLA, bond length alternation; Pyr. Ang., pyramidalization angle. [a] Geometric parameters are computed at the TD-CAM-B3LYP/6-31G* level. [b] Ground and excited state structures are abbreviated GS and ES, respectively. [c] Only the GS structure is presented for II-15, because the ES minimum energy structure has a perpendicular conformation. With the latter experimental and computational results, a physical description of the trends observed in Table II-2 can be summarized as follows. Dyes with small amine substitutions orient such that the nitrogen atom lone pair may participate in conjugation (bis-dipolar), thus leading to the observed blue-shift in absorption. To clarify, the meaning of “size” in this context, it is the width of the substituent, not necessarily the smallest overall moiety. Therefore, the width of the pyrrolidine substituent is less than dimethylamine (dye II-15 vs. II-10). As the lateral size of the substituent increases, the degree of blue-shift is reduced as the bis-dipolar orientation is more difficult to achieve. The observed trend in Stokes shift (II-16 > II-10 > II-11 > II-14) follows the size trend with 123 the anticipated increasing difficulty in adopting the necessary orientation to have the nitrogen atom lone pair in conjugation with the polyene. Dyes II-12 and II-13 (as well as the analogous II-19 and II-20), however, defy the latter description; though they are both smaller than II-15, they do not have higher-energy absorption. Aziridine nitrogen atom’s donating ability to form the bis-dipolar electronic structure would require it to adopt the more strained sp2 hybridization, which is energetically disfavored.24 Thus, dye II-12 has the lowest Stokes shift as it exists in a more cyanine-like conformation in both the ground and excited state, even though it adopts the ‘bis-dipolar’ state by rotation about the C–N bond. Based on the absorption and emission spectra of dye II-13 (both blue-shifted), the azetidine substituent present a unique case. It is small, and thus can adopt the bis-dipolar conformation, and in contrast to the aziridine, rehybridization of its nitrogen atom is not as energetically costly. In fact, iminium formation of azetidines is well documented.25 Yet, it resists conformational change to the structure that favors cyanine-like character in the excited state, presumably because rehybridization is costlier in a small ring, and therefore emits from the bis-dipolar conformation. Dye II-15 finds itself with the correct balance of size, and conformational flexibility to easily traverse from a more bis-dipolar conformer to a more cyanine-like conformations upon excitation, leading to the observed large Stokes shift. In summary, we demonstrate a simple strategy to selectively engineer Stokes shifts for cyanine dyes, important in biomedical engineering and energy capture.26 Stokes shifts of different cyanine dyes can be easily tuned via nitrogen substituents (from 24 nm up to 180 nm). Rotation of the amine substituent upon excitation is responsible for the 124 largest Stokes shifts, and an enhanced Stokes shift is observed when the dye may convert from the bis-dipolar form to the cyanine-like form upon excitation. Some of these dyes applied on TLSC devices demonstrated good results. The large Stokes shift cyanine candidate showed 0.6% PCE with excellent visible transparency >80%.14 II-3-2 Broad absorbing NIR fluorophores for TLCS devices The features of the desired fluorophores for TLCS device are: NIR absorption wavelength, high quantum yield, large Stokes shift and broad absorption profile. In continuation of our efforts to improve the power conversion efficiency of TLSCs, we explored new candidates fitting the criteria of the abovementioned properties. The synthesized cyanine dyes demonstrated good results on the device, since they absorb in NIR with large Stokes shift and high quantum yield. In a new class of dyes, we look for NIR fluorophores that in addition to the high quantum yield and large stokes shift, have a broad absorption band. As shown in Figure II-13, broad absorption would increase the probability of absorbing more photons, which results in higher system efficiency. I I λ λ Figure II-13. Broad absorbing spectra leads to harvesting higher photon numbers 125 During our investigation we found that the acceptor–donor–acceptor (A–D–A) small molecules that are used widely in organic photovoltaic solar cells, have broad absorption spectra. The DRCN7T compound shown in Figure II-14, is an ideal example reported by Chen and co-workers.27 This small molecule with oligothiophene- like backbone and two terminal acceptors, shows broad absorption spectra in solution and film (fluorescent properties were not reported in this work). These dyes usually absorb in the visible region, which can be simply tuned by putting electron donating groups, such as alkoxy, on the thiophene rings and also replacing the terminal groups with stronger molecular acceptors. More recent example of this A–D–A dyes is COi8DFIC (also referred to as O6T-4F, Figure II-14), which has been developed as a nonfullerene acceptor in organic photovoltaics with unprecedented performance.28, 29 Alkoxy electron donating groups on the thieno[3,2-b]thiophene rings of COi8DFIC along with the strong DFIC acceptors led to absorption in the NIR region. There are two important factors in the design of this dye that affect the quantum yield; with the first being the three thieno[3,2-b]thiophene rings in the backbone. These are rigidified via the 6-member rings, which inhibit free rotation, limiting non-radiative pathways in the excited state and resulting in a higher quantum yield, 2. The flat backbone of these dyes could lead to aggregation and lower the quantum yield, but the two geminal di-aryl groups (p(C6H13)- Ph-) on the 6-member rings rotate out of plane and hinder. In this work we planned to introduce nonfullerene acceptor COi8DFIC as the luminescent emitters in NIR- selective harvesting TLSCs. 126 C8H17 C8H17 C8H17 C8H17 S S S S S S S O O S C8H17 C8H17 S N N CN NC NC Acceptor – Donor – Acceptor CN DRCN7T F F Ar NC Ar O S O S CN S S NC S O S O Ar CN Ar F Ar = 4-(n-C6H13)-C6H4 F COi8DFIC Figure II-14. Structures of D-A-D dyes; DRCN7T and COi8DFIC The synthesis of COi8DFIC closely followed the procedure reported previously with small alterations to a few procedures as described in the experimental section30, 31 (Figure II-15). The synthesis commenced with 3-bromothieno[3,2-b]thiophene II-27, and in two steps, bromo ester II-30 was obtained. Meanwhile, the bis(trimethyltin) compound II-33 was made in two steps from dibromide II-31 and reacted with II-30 to furnish the II- 34. Later, demethylation and acidification resulted in di-lactone structure II-36, which following ring opening with 127yrrolid and recyclization, generated the fully cyclized backbone II-38. After a formylation reaction, the di-aldehyde II-39 in the of DFIC acceptor (II-40) was converted to the COi8DFIC as the final product. 127 Br n-BuLi (1 equiv) CO2H n-BuLi (2 equiv) CO2H CO2, Et2O Br2 (1.2 equiv) S S S -78 °C to 0 °C THF Br S 78% S -78 °C to r.t. S II-27 II-28 II-29 EtI (5 equiv) CO2Et K2CO3 (3 equiv) S DMF, 60 °C Br 52% (two steps) S II-30 Br NaOMe (10 equiv) OMe n-BuLi (2.5 equiv) Me3Sn S OMe S CuO (2 equiv) S Me3SnCl (3 equiv) S KI (5 mol%) S THF MeO MeOH -78 °C to r.t., 54% S SnMe3 Br MeO II-31 65 °C, 60% II-33 II-32 CO2Et OMe II-30 (2.5 equiv) Pd(PPh3)4 (10 mol%) S S S BBr3 (6 equiv) Toluene/DMF S S S DCM, r.t., 100% 110 °C, 61% MeO EtO2C II-34 O CO2Et OH O S S S p-TsOH (1.2 equiv) S S S S S S Toluene, 110 °C, 54% S S S HO EtO2C O II-35 O II-36 Ar Ar 4-(n-C6H13)-C6H4MgBr HO HO S S (10 equiv) S p-TsOH (2 equiv) THF, r.t. to 60 °C S S Toluene, r.t. S 81% (two steps) OH II-37 OH Ar Ar Ar = 4-(n-C6H13)-C6H4 Figure II-15. Synthesis of COi8DFIC 128 Figure II-15 (cont’d) Ar Ar Ar Ar O n-BuLi (3 equiv) O S S S DMF (10 equiv) O S S S S S S THF S S S -78 °C to -50 °C O O O Ar 52% Ar Ar Ar II-38 II-39 O F F F Ar NC F Ar O S O S CN NC II-40 CN (5 equiv) S S NC S O DCM, 45 °C S O Ar 90% CN Ar F COi8DFIC F The normalized absorption and emission spectra of COi8DFIC dissolved in chlorobenzene solution and embedded in polymer matrix are plotted in Figure II-16a and II-16b. From solution to polymer matrix, there is a hypsochromic shift of both the absorption and emission spectra: the absorption peak shifts from 770 nm to 745 nm and the emission peak shifts from 831 nm to 808 nm, exhibiting Stokes shift of ~60 nm. The measured quantum yield is 23 ± 1% in chlorobenzene solution and 25 ± 3% in the polymer matrix. The relatively high Stokes shift values as well as high quantum yield demonstrate the potential for these NIR dyes, suggesting that COi8DFIC may be a proper candidate for fabricating on TLSC. 129 e. 50 100 150 200 300 Figure II-16. Data for Coi8DFIC; a. Normalized absorption and emission spectra in chlorobenzene solution, b. Normalized absorption and emission spectra in polymer matrix, c. Current density versus voltage (J–V) characteristics of TLSCs with different concentrations, d. Average EQELSC(λ) spectra of TLSCs with different concentrations, e. Photographs of all the TLSC devices (Permission to utilize the Spartan helmet logo is kindly provided by MSU) 130 TLSC devices with five different COi8DFIC concentrations were made by our collaborator Dr. Chenchen Yang in Prof. Lunt’s group and their photovoltaic performance was characterized. For comparison, TLSC with cyanine dye (Cy7- NHS) was added as a reference device. The current density versus voltage (J–V) characteristics of these TLSCs is shown in Figure II-16c along with average position-dependent external quantum efficiency (EQELSC(λ)) spectra in Figure II-16d. Photographs of all the TLSC devices are shown in Figure II-16e (Permission to utilize the Spartan helmet logo is kindly provided by MSU). The TLSC with COi8DFIC yielded a PCE of 1.24% with an AVT of 74.4%. The spectroscopic properties and extracted photovoltaic parameters are summarized in Table II-7. Table II-7. Spectroscopic properties and TLSC photovoltaic parameters of COi8DFIC Dye lmax (nm)a lem (nm)a Stokes Shift (nm) Φ (%)b PCE (%)c AVT (%)c COi8DFIC 770 831 61 25 1.24 74.4 lmax, absorption maximum; lem, emission maximum; φ, quantum yield; PCE, power conversion efficiency; AVT, average visible transmittance. [a] Absorptions and emissions were recorded in chlorobenzene at rt. [b] Absolute quantum yields were measured by Hamamatsu Quantaurus fluorimeter. [c] PCE and AVT reported for 150 mgL-1. In summary, we have synthesized the nonfullerene acceptor COi8DFIC and utilized it in TLSCs as the luminophore. After device optimization, the TLSCs are shown to achieve a PCE of over 1.2% while the AVT exceeds 74%. This work reports the highest TLSC device efficiency at the highest visible transparency at the time of the report.32 Also, we highlight that the photoluminescent properties of these emerging low bandgap organic molecules provide a promising path for to higher TLSC performance. 131 II-3-3 Ultraviolet and near-infrared dual-band selective-harvesting TLSC Multiple luminophores with various wavelength-selectivity can be incorporated into the LSC waveguide to maximize the spectral coverage of light harvesting33-35, and enhance photovoltaic performance.36, 37 However, coupling or reabsorption between different luminophores often leads to a reduction in the efficacy of this approach.38 In this work, we introduce highly luminescent phosphorescent nanoclusters (NCs) and fluorescent organic molecules into TLSCs as isolated UV and NIR selective-harvesting luminophores, respectively. The NCs selectively harvest UV photons while exhibiting near-unity PL quantum yields (QY) and massive downshift of the luminescence into the NIR, without the use of heavy or toxic elements such as lead.9 To effectively pair these emitters and prevent deleterious reabsorption loss of the nanocluster emission in the NIR absorbing organic fluorophore, we demonstrate a strategy to isolate the absorption/emission bands. The dual-band TLSC device is composed of two distinct waveguides as shown in Figure II-17 with the UV component coated in polymer matrix on one waveguide and the NIR component on the other. An air gap is utilized to optically isolate the waveguided luminescence in each panel to prevent reabsorption. 132 PV PV UV Low-index component Gap NIR component Transmitted VIS Figure II-17. Schematic of the working principle of the dual-band selective harvesting TLSC The top UV component is based on phosphorescent hexanuclear NCs, where the chemical structure of Cs2Mo6I8(CF3CF2COO)6 NC is shown in Figure II-18 (The NCs were synthesized by our collaborators in chemical engineering). Substitution of the apical halide positions has been shown previously to be an effective approach to increase quantum yields above 50%.9, 39 Various terminating ligands ((CF3)n chain length) were synthesized and tested to maximize the QY with the composition above providing the highest value. We note that the chemical composition of the NC does not contain any hazardous heavy metal ions, which makes the deployment more environment friendly. The normalized absorption and emission spectra of the NC in polymer are shown in Figure II-18. The spectra show absorption cut-off at the UV/VIS border and NIR emission onset at the VIS/NIR border with a massive downshift over 300 nm and a corresponding QY of 80 ± 5 in the polymer matrix (75 ± 5% in acetonitrile), which makes these NCs a practical UV selective-harvesting luminophore for TLSC applications. 133 1 Abs/Em (normalized) 0 400 600 800 Wavelength (nm) Figure II-18. Molecular structure, normalized absorption and emission spectra of Cs2Mo6I8(CF3CF2COO)6 nanocluster The bottom waveguide is based on NIR fluorescent small molecules. Two different organic luminophores are demonstrated as NIR selective harvesters. The first being COi8DFIC, as discussed in a previous section (II-3-2). The absorption peak is 745 nm while the emission peak is at 808 nm, resulting in a Stokes shift of ~60 nm and QY of 25 ± 3% in polymer matrix (23 ± 1% in chlorobenzene). The second dye is a BODIPY derivative with high QY in the NIR.40 The molecular structure, normalized absorption, and emission spectra of BODIPY in polymer matrix is shown in Figure II-19. Compared to COi8DFIC, the absorption and emissions peaks of BODIPY are narrower with a smaller Stokes shift (10 nm), but the significantly higher QY of 40 ± 3% in polymer matrix (41 ± 2% in hexane) is among the highest values for this NIR emission range. 134 1 Abs/Em (normalized) N N B F F NH HN 0 BODIPY 400 500 600 700 800 900 Wavelength (nm) Figure II-19. Molecular structure, normalized absorption and emission spectra of BODIPY After optimization of concentration, dual-band TLSC devices with two luminophore combinations (NC+COi8DFIC and NC+BODIPY) were fabricated and their photovoltaic performance was characterized. For comparison, the TLSC with NC-only was added as a reference device. The current density versus voltage (J–V) characteristics of these TLSCs are shown in Figure II-20a along with average position-dependent external quantum efficiency (EQELSC(λ)) spectra in Figure II-20b. 60 0 4 50 J (mA cm-2) NC-only Int (mAcm-2) EQELSC% JSC -1 NC+COi8DFIC 40 3 NC+BODIPY 30 -2 2 20 -3 1 10 -4 0 0 0.0 0.2 0.4 0.6 0.8 1.0 1.2 300 400 500 600 700 800 900 V (V) Wavelength (nm) Figure II- 20. A. J–V characteristics of TLSCs, b. Average EQELSC(λ) spectra of TLSCs 135 The quantum yield and extracted photovoltaic parameters are summarized in Table II-8. PCEs reach 2.9 ± 0.1% and 3.01 ± 0.07% for NC+COi8DFIC and NC+BODIPY TLSCs, respectively, with color metrics suitable for the window industry. Table II-8. Spectroscopic properties and TLSC photovoltaic parameters of COi8DFIC TLSCs Dyes Φ (%)a PCE (%) AVT (%) NC 80 1 + 2.9 65.6 COi8DFIC 25 NC 80 2 + 3.1 75.8 BODIPY 40 [a] Quantum yields were measured in polymer matrix. In summary, by combining highly emissive phosphorescent hexanuclear metal halide NCs and organic luminophores as isolated UV and NIR selective-harvesting luminophores, we have designed and demonstrated dual-band selective-harvesting TLSC devices. Harvesting non-visible photons from both UV and NIR portions of solar spectrum leads to PCE > 3%, with good wavelength-selectivity that results in AVT > 75%. This work reports the highest PCE of any transparent photovoltaic (TPV) devices with AVT greater than 70% at the time of publication.41 136 II-4 Future work II-4-1 Further investigations on tuning the Stokes shift and QY of cyanines We previously reported a general strategy to tune the Stokes shift of the cyanine dyes by substitution of different amines at C4 position which would maintain or break conjugation leading to two distinct ground state conformations. As shown in Figure II-21a, the C2 position on cyanine’s methine backbone has the potential to affect more than the C-4 (II-41). Amination at this position could also disrupt conjugation, leading to a greater extent of blue shifting, as compared to C-4, because it would shorten the conjugation to a greater extent. The synthesis of C2-halogenated cyanines is under study in our lab. In a parallel study our computational collaborator, Professor Levine hypothesized that, locking the pyrrolidine ring to the methine chain backbone such as that shown in structure (II-42), could lead to a massive Stokes shift (Figure II-21b). The synthetic strategy toward making this molecule is under study. a. b. NR2 N N N N N I I II-41 II-42 Figure II-21. a. Amine C2-substituted cyanines, b. asymmetric cyclized aminated cyanine We have previously discussed cyanine’s wide utility due to their unique structural characteristics. Although improving the quantum yield of cyanines was evaluated with different approaches, for most cases the efficiency does not rise above 25-35% beyond 700 nm. Schnermann and coworkers have shown a QY increase of more than 4-fold upon 137 restricting bond rotations of the Cy5 methine chain, although this approach fails when the methine length increases from five to seven.42, 43 Since Cy5 absorption is primarily in the visible region, they fall short of what is required for transparent solar concentrators. In addition, red-shifted fluorophores are more suitable for bio imaging as well. Our plan entails modification of the indoline based head groups (with higher donor strength) on Cy5, in order to optimize the absorption in the NIR region. Next, we would restrain the conformation to increase the QY. Five proposed head groups are depicted in Figure II- 22; two full structures with the head groups are shown as examples. In addition, we would install an amine at the center of the chain to increase the stokes shift and minimize the integral overlap. Proposed Head Groups N X S X O O S X X N X O O N R R N R R N N O O S S X O X O Examples of Proposed Structures Figure II-22. Proposed head groups to redshift the Cy5 core and, proposed new Cy5 structures 138 II-4-2 Donor-acceptor-donor dyes as a potential tools in TLSCs and bio imaging We have shown the application of acceptor–donor–acceptor (A–D–A) fluorophore COi8DFIC as the luminescent emitters in NIR-selective harvesting TLSCs. The other potential candidate could be donor–acceptor–donor(D–A–D) NIR I/II chromophores which have gained considerable attention as a result of their unique structural and photophysical properties. These include high quantum yields, a high stokes shift , high coefficient of absorption, all while absorbing and emitting outside the visible spectrum.44 The general structure of D–A–D that are under evaluation in our lab is depicted in Figure II-23. Our goal is to make a library of these dyes by tuning the donating ability of the substituents and perturbing the electronic structure of acceptor by having different atoms at X and Y. X N N R R N N Y X, Y = S, Se II-43 R = OR, NR2 Figure II-23. General structure of D–A–D NIR I/II fluorophores 139 II-5 Experimental section II-5-1 General remarks: Molecular sieves (4Å) were dried at 160 °C under 0.25 mtorr vacuum prior to use. Unless otherwise mentioned, solvents were purified as follows. CHCl3 (amylene stabilized) was purchased from Sigma Aldrich and incubated over 4Å MS for 48 h prior to use. Toluene and CH2Cl2 were dried over CaH2 whereas THF and Et2O were dried over sodium (dryness was monitored by colorization of benzophenone ketyl radical); they were freshly distilled prior to use. Acetonitrile and DMF for reactions was HPLC grade from Sigma-Aldrich. NMR spectra were obtained using a 500 MHz Varian NMR spectrometer and referenced using the residual 1H peak from the deuterated solvent. Waters 2795 (Alliance HT) instrument was used for HRMS (ESI) analysis with polyethylene glycol (PEG-400-600) as a reference. UV-Vis was performed on Agilent Cary 100 series machine and PL was recorded on Fluorolog by ISA instrument. Quantum yield measurement was performed on absolute PL quantum yield spectrometer C11347 by Hamamatsu. Column chromatography was performed using Silicycle 60Å, 35-75 µm silica gel. Pre-coated 0.25 mm thick silica gel 60 F254 plates were used for analytical TLC and visualized using UV light, potassium permanganate stain, p-anisaldehyde stain or phosphomolybdic acid in EtOH stain. 140 II-5-2 General synthesis of amine substituted cyanines: R1 R2 N H R1 R2 Cl N N N DIPEA, ACN N N I 70 ºC I II-6 II-9 Amine substituted cyanines II-9 were synthesized according to the previous reported procedures.17 To a solution of II-6 (74 mg, 0.10 mmol), diisopropylethylamine (DIPEA) (35 µL, 2 equiv, 0.20 mmol) in acetonitrile (2 mL) was added amine (20 equiv, 2.0 mmol) under nitrogen in a sealed tube. The mixture was stirred at 70 °C and the reaction was monitored by LC-MS. Upon completion, typically in 48 h, the mixture was concentrated under reduced pressure and purified by flash column (100% DCM gradually to 5% MeOH/DCM). The products were isolated as a dark solids. II-5-2-1 Analytical Data N N N I II-10 2-(CAN-2-(CAN-2-(dimethylamino)-3-(2-(CAN-1,3,3-trimethylindolin-2- ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-1,3,3-trimethyl-3H-indol-1-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark green solid (40 mg, 0.064 mmol, 64%). 141 1H-NMR (500 MHz, Chloroform-d): δ 7.40 (d, J = 13.1 Hz, 2H), 7.23 (td, J = 8.1, 7.4, 1.5 Hz, 4H), 7.01 (t, J = 7.4 Hz, 2H), 6.88 (d, J = 7.9 Hz, 2H), 5.56 (d, J = 13.1 Hz, 2H), 3.61 (s, 6H), 3.39 (s, 6H), 2.46 (t, J = 6.6 Hz, 4H), 1.79 (p, J = 6.6 Hz, 2H), 1.59 (s, 12H). 13C-NMR (126 MHz, Chloroform-d): δ 175.55, 167.84, 143.54, 140.28, 139.84, 128.22, 122.73, 122.08, 121.97, 108.50, 94.06, 53.53, 47.86, 47.60, 29.48, 25.40, 21.56. HRMS(ESI+): calcd for C34H42N3+ [M]+ 492.3379, found 492.3378. N N N I II-11 2-(CAN-2-(CAN-2-(ethyl(methyl)amino)-3-(2-(CAN-1,3,3-trimethylindolin-2- ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-1,3,3-trimethyl-3H-indol-1-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (39 mg, 0.062 mmol, 62%). 1H-NMR (500 MHz, Chloroform-d): δ 7.46 (d, J = 13.4 Hz, 2H), 7.33 – 7.24 (m, 4H), 7.08 (t, J = 7.4 Hz, 2H), 6.97 (d, J = 7.9 Hz, 2H), 5.72 (d, J = 13.4 Hz, 2H), 3.79 (q, J = 7.0 Hz, 2H), 3.48 (s, 6H), 3.41 (s, 3H), 2.47 (t, J = 6.5 Hz, 4H), 1.81 (p, J = 6.6 Hz, 2H), 1.60 (s, 12H), 1.37 (t, J = 7.0 Hz, 3H). 142 13C-NMR (126 MHz, Chloroform-d): δ 175.03, 169.15, 143.30, 141.83, 139.94, 128.44, 124.26, 123.41, 121.97, 109.15, 95.86, 53.52, 47.90, 44.73, 31.24, 29.27, 24.94, 21.83, 14.98. HRMS(ESI+): calcd for C35H44N3+ [M]+ 506.3535, found 506.3525. N N N I II-12 1,3,3-Trimethyl-2-(CAN-2-(CAN-2-(2-methylaziridin-1-yl)-3-(2-(CAN-1,3,3- trimethylindolin-2-ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3H-indol-1-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (30 mg, 0.047 mmol, 47%). 1H-NMR (500 MHz, Chloroform-d): δ 8.01 (d, J = 13.7 Hz, 2H), 7.38 – 7.26 (m, 4H), 7.14 (t, J = 7.4 Hz, 2H), 7.05 (d, J = 7.9 Hz, 2H), 5.88 (d, J = 13.7 Hz, 2H), 3.57 (s, 6H), 2.57 (t, J = 6.0 Hz, 4H), 1.84 – 1.76 (m, 3H), 1.69 – 1.59 (m, 14H), 1.46 (d, J = 5.4 Hz, 3H). 13C-NMR (126 MHz, Chloroform-d): δ 170.91, 170.12, 143.07, 140.20, 139.76, 128.61, 124.61, 124.14, 121.99, 109.76, 98.11, 48.27, 39.06, 36.94, 31.66, 28.61, 28.47, 25.95, 20.86, 18.09. HRMS(ESI+): calcd for C35H42N3+ [M]+ 504.3379, found 504.3375. 143 N N N I II-13 2-(CAN-2-(CAN-2-(144yrrolidi-1-yl)-3-(2-(CAN-1,3,3-trimethylindolin-2- ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-1,3,3-trimethyl-3H-indol-1-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (49 mg, 0.078 mmol, 78%). 1H-NMR (500 MHz, Chloroform-d): δ 7.24 – 7.16 (m, 6H), 6.96 (t, J = 7.5 Hz, 2H), 6.77 (d, J = 7.7 Hz, 2H), 5.32 (d, J = 12.8 Hz, 2H), 4.93 (t, J = 7.6 Hz, 4H), 3.25 (s, 6H), 2.71 (p, J = 7.6 Hz, 2H), 2.56 – 2.49 (m, 4H), 1.86 – 1.83 (m, 2H), 1.64 (s, 12H). 13C-NMR (126 MHz, Chloroform-d): δ 169.77, 165.86, 143.70, 139.75, 134.78, 127.96, 121.99, 121.95, 107.61, 92.32, 62.46, 47.02, 29.83, 29.27, 27.22, 20.79, 19.31. HRMS(ESI+): calcd for C35H42N3+ [M]+ 504.3379, found 504.3382. N N N I II-14 2-(CAN-2-(CAN-2-(diethylamino)-3-(2-(CAN-1,3,3-trimethylindolin-2- ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-1,3,3-trimethyl-3H-indol-1-ium iodide. 144 The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (21 mg, 0.032 mmol, 32%). 1H-NMR (500 MHz, Chloroform-d): δ 7.52 (d, J = 13.6 Hz, 2H), 7.34 – 7.26 (m, 4H), 7.11 (m, 2H), 7.02 (d, J = 7.9 Hz, 2H), 5.80 (d, J = 13.6 Hz, 2H), 3.65 (q, J = 6.9 Hz, 4H), 3.52 (s, 6H), 2.49 (t, J = 6.5 Hz, 4H), 1.82 (p, J = 6.5 Hz, 2H), 1.60 (s, 12H), 1.28 (t, J = 6.9 Hz, 6H). 13C-NMR (126 MHz, Chloroform-d): δ 174.15, 169.83, 143.19, 142.52, 140.06, 128.57, 125.76, 123.76, 121.97, 109.50, 96.95, 49.47, 48.03, 31.36, 29.07, 24.88, 21.98, 14.84. HRMS(ESI+): calcd for C36H46N3+ [M]+ 520.3690, found 520.3692. N N N I II-15 1,3,3-Trimethyl-2-(CAN-2-(CAN-2-(145yrrolidine-1-yl)-3-(2-(CAN-1,3,3-trimethylindolin- 2-ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3H-indol-1-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (15 mg, 0.023 mmol, 23%). 1H-NMR (500 MHz, Chloroform-d): δ 7.42 (d, J = 12.7 Hz, 2H), 7.19 (m, 4H), 6.94 (t, J = 7.4 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 5.27 (d, J = 12.7 Hz, 2H), 4.32 (d, J = 6.5 Hz, 4H), 3.22 (s, 6H), 2.59 (t, J = 6.2 Hz, 4H), 2.10 (m, 4H), 1.79 (t, J = 6.3 Hz, 2H), 1.70 (s, 12H). 145 13C-NMR (126 MHz, cdcl3): δ 173.07, 165.22, 143.92, 140.02, 135.14, 127.72, 122.03, 121.53, 121.22, 107.08, 91.76, 55.86, 46.98, 29.58, 29.43, 28.77, 24.16, 20.91. HRMS(ESI+): calcd for C36H44N3+ [M]+ 518.3535, found 518.3536. N N N I II-16 1,3,3-Trimethyl-2-(CAN-2-(CAN-2-(piperidin-1-yl)-3-(2-(CAN-1,3,3-trimethylindolin-2- ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3H-indol-1-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (72 mg, 0.054 mmol, 54%). 1H-NMR (500 MHz, Chloroform-d): δ 7.50 (d, J = 13.2 Hz, 2H), 7.33 – 7.22 (m, 4H), 7.06 (t, J = 7.4 Hz, 2H), 6.95 (d, J = 7.9 Hz, 2H), 5.68 (d, J = 13.2 Hz, 2H), 3.85 (t, J = 5.0 Hz, 4H), 3.46 (s, 6H), 2.47 (t, J = 6.7 Hz, 4H), 1.96-1.92 (m, 2H), 1.90-1.86 (m, 4H), 1.84-1.82 (m, 2H), 1.62 (s, 12H). 13C-NMR (126 MHz, Chloroform-d): δ 175.57, 168.39, 143.43, 140.15, 139.75, 128.36, 123.79, 123.06, 121.89, 108.84, 95.03, 56.80, 47.63, 28.96, 28.15, 24.94, 24.28, 21.63, 18.91. HRMS(ESI+): calcd for C37H46N3+ [M]+ 532.3692, found 532.3690. 146 N N N I II-17 2-(CAN-2-(CAN-2-(dimethylamino)-3-(CAN-2-(3-ethyl-1,1-dimethyl-1,3-dihydro-2H- benzo[e]indol-2-ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3-ethyl-1,1-dimethyl-1H- benzo[e]indol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (41 mg, 0.055 mmol, 55%). 1H-NMR (500 MHz, Chloroform-d): δ 8.07 (d, J = 8.5 Hz, 2H), 7.83 (dd, J = 8.5, 4.4 Hz, 4H), 7.57 (d, J = 13.3 Hz, 2H), 7.51 (ddd, J = 8.3, 6.8, 1.3 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 5.69 (d, J = 13.3 Hz, 2H), 4.04 (q, J = 7.2 Hz, 4H), 3.65 (s, 6H), 2.50 (t, J = 6.6 Hz, 4H), 1.93 (s, 12H), 1.86 – 1.81 (m, 2H), 1.40 (t, J = 7.2 Hz, 6H). 13C-NMR (126 MHz, Chloroform-d): δ 174.46, 168.95, 140.52, 139.85, 131.82, 130.89, 130.18, 129.89, 128.49, 127.41, 123.90, 122.00, 121.91, 109.74, 93.65, 49.72, 47.83, 38.59, 28.97, 25.34, 21.74, 12.03. HRMS(ESI+): calcd for C44H50N3+ [M]+ 620.4005, found 620.4008. 147 N N N I II-18 3-Ethyl-2-(CAN-2-(CAN-2-(ethyl(methyl)amino)-3-(CAN-2-(3-ethyl-1,1-dimethyl-1,3- dihydro-2H-benzo[e]indol-2-ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-1,1-dimethyl- 1H-benzo[e]indol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (57 mg, 0.075 mmol, 75%). 1H-NMR (500 MHz, Chloroform-d): δ 8.06 (d, J = 8.4 Hz, 2H), 7.86 (dd, J = 8.7, 2.1 Hz, 4H), 7.63 (d, J = 13.6 Hz, 2H), 7.53 (ddd, J = 8.4, 6.8, 1.3 Hz, 2H), 7.36 (ddd, J = 8.1, 6.9, 1.1 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H), 5.82 (d, J = 13.6 Hz, 2H), 4.11 (q, J = 7.2 Hz, 4H), 3.80 (q, J = 7.0 Hz, 2H), 3.42 (s, 3H), 2.50 (t, J = 6.4 Hz, 4H), 1.92 (s, 12H), 1.85 (p, J = 6.5 Hz, 2H), 1.43 – 1.40 (m, 9H). 13C-NMR (126 MHz, Chloroform-d): δ 173.76, 170.16, 141.76, 139.68, 132.27, 131.18, 130.46, 130.02, 128.35, 127.53, 124.33, 124.23, 121.83, 110.09, 95.39, 53.44, 49.99, 44.59, 39.03, 24.99, 21.96, 15.12, 12.24. HRMS(ESI+): calcd for C45H52N3+ [M]+ 634.4161, found 634.4171. 148 N N N I II-19 3-Ethyl-2-(CAN-2-(CAN-3-(CAN-2-(3-ethyl-1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2- ylidene)ethylidene)-2-(2-methylaziridin-1-yl)cyclohex-1-en-1-yl)vinyl)-1,1-dimethyl-1H- benzo[e]indol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (36 mg, 0.047 mmol, 47%). 1H-NMR (500 MHz, Chloroform-d): δ 8.14 (d, J = 13.7 Hz, 2H), 8.10 – 8.04 (m, 2H), 7.88 (dd, J = 8.5, 4.2 Hz, 4H), 7.55 (ddd, J = 8.3, 6.8, 1.3 Hz, 2H), 7.39 (ddd, J = 8.0, 6.8, 1.0 Hz, 2H), 7.35 (d, J = 8.8 Hz, 2H), 5.94 (d, J = 13.7 Hz, 2H), 4.18 (q, J = 7.3 Hz, 4H), 2.79 – 2.77 (m, 1H), 2.70 (d, J = 5.8 Hz, 1H), 2.58 (t, J = 6.2 Hz, 4H), 2.43 (d, J = 3.5 Hz, 1H), 1.98 (d, J = 7.4 Hz, 13H), 1.86 – 1.82 (m, 2H), 1.56 (d, J = 5.4 Hz, 3H), 1.44 (t, J = 7.2 Hz, 6H). 13C-NMR (126 MHz, Chloroform-d): δ 170.68, 170.28, 139.50, 139.11, 132.75, 131.45, 130.61, 130.07, 128.30, 127.64, 124.54, 124.01, 121.93, 110.27, 97.17, 50.26, 39.37, 37.12, 28.16, 28.04, 25.94, 20.92, 18.37, 12.33. HRMS(ESI+): calcd for C45H50N3+ [M]+ 632.4005, found 632.4009. 149 N N N I II-20 2-(CAN-2-(CAN-2-(150yrrolidi-1-yl)-3-(CAN-2-(3-ethyl-1,1-dimethyl-1,3-dihydro-2H- benzo[e]indol-2-ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3-ethyl-1,1-dimethyl-1H- benzo[e]indol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (64 mg, 0.084 mmol, 84%). 1H-NMR (500 MHz, Chloroform-d): δ 8.07 (d, J = 8.6 Hz, 2H), 7.78 (dd, J = 13.7, 8.4 Hz, 4H), 7.48 (ddd, J = 8.3, 6.8, 1.3 Hz, 2H), 7.38 (d, J = 12.8 Hz, 2H), 7.29 (ddd, J = 8.0, 6.8, 1.0 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 5.43 (d, J = 12.7 Hz, 2H), 5.01 (t, J = 7.5 Hz, 4H), 3.88 (q, J = 7.2 Hz, 4H), 2.75 (p, J = 7.5 Hz, 2H), 2.55 (t, J = 6.2 Hz, 4H), 1.96 (s, 12H), 1.90 – 1.84 (m, 2H), 1.31 (t, J = 7.2 Hz, 6H). 13C-NMR (126 MHz, Chloroform-d): δ 169.26, 166.64, 140.07, 134.72, 131.06, 130.49, 129.81, 129.72, 128.65, 127.24, 123.39, 122.06, 117.62, 109.25, 91.46, 62.48, 49.04, 37.71, 28.66, 27.22, 20.84, 19.31, 11.59. HRMS(ESI+): calcd for C45H50N3+ [M]+ 632.4005, found 632.4007. 150 N N N I II-21 2-(CAN-2-(CAN-2-(diethylamino)-3-(CAN-2-(3-ethyl-1,1-dimethyl-1,3-dihydro-2H- benzo[e]indol-2-ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3-ethyl-1,1-dimethyl-1H- benzo[e]indol-3-ium iodide The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (36 mg, 0.046 mmol, 46%). 1H-NMR (500 MHz, Chloroform-d): δ 8.07 (d, J = 8.5 Hz, 2H), 7.89 (d, J = 8.9 Hz, 4H), 7.69 (d, J = 13.7 Hz, 2H), 7.58 – 7.51 (m, 2H), 7.42 – 7.37 (m, 2H), 7.34 (d, J = 8.8 Hz, 2H), 5.89 (d, J = 13.7 Hz, 2H), 4.15 (q, J = 7.2 Hz, 4H), 3.70 (q, J = 6.9 Hz, 4H), 2.53 (t, J = 6.4 Hz, 4H), 1.93 (s, 12H), 1.89 – 1.85 (m, 2H), 1.44 (t, J = 7.2 Hz, 6H), 1.35 (t, J = 6.9 Hz, 6H). 13C-NMR (126 MHz, Chloroform-d): δ 173.00, 170.56, 142.05, 139.64, 132.46, 131.29, 130.56, 130.10, 128.33, 127.57, 125.62, 124.37, 121.82, 110.20, 96.22, 50.06, 49.39, 39.18, 28.59, 28.44, 25.01, 22.05, 14.96, 12.31. HRMS (ESI+): calcd for C46H54N3+ [M]+ 648.4319, found 648.4318. 151 N N N I II-22 3-Ethyl-2-(CAN-2-(CAN-3-(CAN-2-(3-ethyl-1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2- ylidene)ethylidene)-2-(152yrrolidine-1-yl)cyclohex-1-en-1-yl)vinyl)-1,1-dimethyl-1H- benzo[e]indol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (56 mg, 0.072 mmol, 72%). 1H-NMR (500 MHz, Chloroform-d): δ 8.08 (d, J = 8.6 Hz, 2H), 7.75 (dd, J = 16.0, 8.4 Hz, 4H), 7.53 (d, J = 12.7 Hz, 2H), 7.44 (dd, J = 8.4, 6.8 Hz, 2H), 7.25 (t, J = 7.5 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 5.38 (d, J = 12.7 Hz, 2H), 4.34 (d, J = 6.4 Hz, 4H), 3.84 (q, J = 7.6, 7.0 Hz, 4H), 2.62 (t, J = 6.1 Hz, 4H), 2.12 (q, J = 4.7, 3.1 Hz, 4H), 1.99 (s, 12H), 1.81 (p, J = 6.4 Hz, 2H), 1.29 (t, J = 7.3 Hz, 6H). 13C-NMR (126 MHz, Chloroform-d): δ 172.74, 165.92, 140.25, 135.05, 130.89, 130.28, 129.65, 129.62, 128.76, 127.03, 123.10, 122.11, 120.64, 109.17, 91.03, 55.93, 48.99, 37.51, 28.81, 28.78, 24.30, 20.89, 11.50. HRMS (ESI+): calcd for C46H52N3+ [M]+ 646.4161, found 646.4163. 152 N N N I II-23 3-Ethyl-2-(CAN-2-(CAN-3-(CAN-2-(3-ethyl-1,1-dimethyl-1,3-dihydro-2H-benzo[e]indol-2- ylidene)ethylidene)-2-(piperidin-1-yl)cyclohex-1-en-1-yl)vinyl)-1,1-dimethyl-1H- benzo[e]indol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (66 mg, 0.084 mmol, 84%). 1H-NMR (500 MHz, Chloroform-d): δ 8.06 (d, J = 8.6 Hz, 2H), 7.84 (d, J = 8.5 Hz, 4H), 7.68 (d, J = 13.3 Hz, 2H), 7.51 (ddd, J = 8.3, 6.8, 1.3 Hz, 2H), 7.34 (ddd, J = 8.0, 6.8, 1.0 Hz, 2H), 7.27 (d, J = 8.7 Hz, 2H), 5.78 (d, J = 13.3 Hz, 2H), 4.07 (q, J = 7.2 Hz, 4H), 3.79 (t, J = 4.8 Hz, 4H), 2.48 (t, J = 6.6 Hz, 4H), 1.95 – 1.80 (m, 20H), 1.40 (t, J = 7.2 Hz, 6H). 13C-NMR (126 MHz, Chloroform-d): δ 174.14, 169.56, 140.35, 139.77, 131.99, 131.07, 130.38, 129.99, 128.39, 127.46, 124.08, 124.04, 121.86, 110.03, 94.84, 56.78, 49.78, 38.85, 28.48, 28.23, 25.07, 24.57, 21.83, 12.18. HRMS (ESI+): calcd for C47H54N3+ [M]+ 660.4318, found 660.4318. 153 N N N I II-24 3-Ethyl-2-(CAN-2-(CAN-3-((Z)-2-(3-ethylbenzo[d]thiazol-2(3H)-ylidene)ethylidene)-2- (154yrrolidine-1-yl)cyclohex-1-en-1-yl)vinyl)benzo[d]thiazol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (29 mg, 0.046 mmol, 46%). 1H NMR (500 MHz, Chloroform-d) δ 7.58 (dd, J = 8.3, 1.2 Hz, 2H), 7.42 (ddd, J = 8.6, 7.6, 1.2 Hz, 2H), 7.36 – 7.31 (m, 2H), 7.27 – 7.20 (m, 4H), 5.87 (d, J = 12.7 Hz, 2H), 4.24 (q, J = 7.3 Hz, 4H), 3.46 (s, 6H), 2.45 (t, J = 6.5 Hz, 4H), 1.84 – 1.80 (m, 2H), 1.47 (t, J = 7.2 Hz, 6H). 13C NMR (126 MHz, Chloroform-d) δ 141.48, 127.63, 124.71, 124.07, 122.31, 111.13, 92.69, 47.76, 41.33, 29.71, 22.01, 12.31. N N N I II-25 2-(CAN-2-(CAN-2-(diethylamino)-3-((Z)-2-(3-ethylbenzo[d]thiazol-2(3H)- ylidene)ethylidene)cyclohex-1-en-1-yl)vinyl)-3-ethylbenzo[d]thiazol-3-ium iodide. 154 The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (38 mg, 0.058 mmol, 58%). 1H NMR (500 MHz, Chloroform-d) δ 7.59 (d, J = 8.0, 1.2 Hz, 2H), 7.48 – 7.39 (m, 4H), 7.32 (d, J = 8.2 Hz, 2H), 7.26 – 7.20 (m, 2H), 6.02 (d, J = 13.0 Hz, 2H), 4.33 (q, J = 7.3 Hz, 4H), 3.59 (q, J = 7.1 Hz, 4H), 2.51 (t, J = 6.3 Hz, 4H), 1.85 (q, J = 6.4 Hz, 2H), 1.48 (t, J = 7.3 Hz, 6H), 1.31 (t, J = 7.0 Hz, 6H). 13C NMR (126 MHz, Chloroform-d) δ 161.30, 142.65, 141.53, 127.87, 124.93, 124.41, 122.31, 122.21, 111.69, 111.14, 94.81, 49.60, 41.79, 29.71, 25.77, 21.93, 14.22. N N N I II-26 3-Ethyl-2-(CAN-2-(CAN-3-((Z)-2-(3-ethylbenzo[d]thiazol-2(3H)-ylidene)ethylidene)-2- (155yrrolidine-1-yl)cyclohex-1-en-1-yl)vinyl)benzo[d]thiazol-3-ium iodide. The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark solid (54 mg, 0.082 mmol, 82%). 1H NMR (500 MHz, Chloroform-d): δ 7.47 (d, J = 7.7 Hz, 2H), 7.31 (t, J = 7.7 Hz, 2H), 7.14 – 7.05 (m, 4H), 7.02 (d, J = 8.2 Hz, 2H), 5.51 (d, J = 12.0 Hz, 2H), 4.17 (s, 4H), 4.04 (q, J = 7.2 Hz, 4H), 2.61 – 2.53 (m, 4H), 2.11 (s, 4H), 1.86 – 1.81 (m, 2H), 1.38 (t, J = 7.2 Hz, 6H). 155 13C NMR (126 MHz, Chloroform-d): δ 156.88, 141.65, 137.22, 126.98, 124.54, 122.91, 122.15, 119.87, 109.86, 88.91, 55.99, 40.37, 28.82, 24.62, 20.94, 11.73. 156 II-5-3 Synthesis of COi8DFIC The dye COi8DFIC was synthesized according to the following scheme: Br n-BuLi (1 equiv) CO2H n-BuLi (2 equiv) CO2H CO2, Et2O Br2 (1.2 equiv) S S S -78 °C to 0 °C THF Br S S -78 °C to r.t. S II-27 II-28 II-29 EtI (5 equiv) CO2Et K2CO3 (3 equiv) S DMF, 60 °C Br S II-30 Br NaOMe (10 equiv) OMe n-BuLi (2.5 equiv) Me3Sn S OMe S CuO (2 equiv) S Me3SnCl (3 equiv) S KI (5 mol%) S THF MeO MeOH, 65 °C -78 °C to r.t. S SnMe3 Br MeO II-31 II-33 II-32 CO2Et OMe II-30 (2.5 equiv) Pd(PPh3)4 (10 mol%) S S S BBr3 (6 equiv) Toluene/DMF S S S DCM, r.t. 110 °C MeO EtO2C II-34 O CO2Et OH O S S S p-TsOH (1.2 equiv) S S S S S S Toluene, 110 °C S S S HO EtO2C O II-35 O II-36 157 II-5-3 Synthesis of COi8DFIC (cont’d) Ar Ar 4-(n-C6H13)-C6H4MgBr HO HO S S (10 equiv) S p-TsOH (2 equiv) THF, r.t. to 60 °C S S Toluene, r.t. S 81% (two steps) OH OH Ar Ar II-37 Ar = 4-(n-C6H13)-C6H4 Ar Ar Ar Ar O n-BuLi (3 equiv) O S S S DMF (10 equiv) O S S S S S S THF S S S -78 °C to -50 °C O O O Ar 52% Ar Ar Ar II-38 II-39 O F F F Ar NC F Ar O S O S CN NC II-40 CN (5 equiv) S S NC S O DCM, 45 °C S O Ar 90% CN Ar F COi8DFIC F II-5-3-1 Synthesis of compound II-28 Br n-BuLi (1 equiv) CO2H CO2, Et2O S S -78 °C to 0 °C S 78% S II-27 II-28 Following the reported procedure31 n-BuLi (2.5 M in hexane, 4 mL, 10 mmol) was added dropwise to a solution of 3-bromothieno[3,2-b]thiophene II-27 (2.19 g, 10 mmol) in dry diethyl ether (30 mL) at -78 °C. The mixture stirred for 1 hour at this temperature and 158 then CO2 gas was bubbled in the reaction for 30 minutes. The reaction warmed up to 0°C and 1 M, NaOH (100 mL) was added to quench it. The solution was extracted with diethyl ether (2 x 50 mL). The organic layers were discard and 3 M, HCl was added to aqueous layer to adjust the pH at 3. The white solid was filtered and dried to give the product (1.43 g, 78%) 1H NMR (500 MHz, Chloroform-d) δ 8.35 (d, J = 1.6 Hz, 1H), 7.53 (dd, J = 5.3, 1.6 Hz, 1H), 7.31 (d, J = 5.3 Hz, 1H). 13C NMR (126 MHz, Chloroform-d) δ 166.88, 139.08, 138.77, 136.79, 129.76, 124.94, 119.11. II-5-3-2 Synthesis of compound II-30 CO2H n-BuLi (2 equiv) CO2H EtI (5 equiv) CO2Et Br2 (1.2 equiv) K2CO3 (3 equiv) S S S THF Br DMF, 60 °C Br S -78 °C to r.t. S 52% (two steps) S II-28 II-29 II-30 Following the reported procedure31 n-BuLi (2.5 M in hexane, 4.96 mL, 12.4 mmol) was added dropwise to a solution of II-28 (1.14 g, 6.2 mmol) in dry THF (25 mL) at -78 °C. After stirring for 30 minutes at this temperature, bromine was added dropwise (333 μL, 7.5 mmol). The solution slowly warmed up to the room temperature and stirred overnight. The reaction was quenched with 3 M, HCl (10 mL) and extracted with diethyl ether (3 × 30 mL). The combined organic layers washed with NaCl, dried with anhydrous Na2SO4 and concentrated under reduced pressure to give the acid as a white solid. The 159 acid crude was dissolved in DMF (10 mL) and, ethyl iodide (4.85 g, 31 mmol) and K2CO3 (2.55 g, 18.6 mmol), were added. The reaction heated at 60 °C and stirred for 5 hours at this temperature. The solution cooled to room temperature then, the mixture extracted with DCM (25 mL) and H2O (25 mL). The organic layer dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was then purified by column chromatography (silica, DCM/petroleum ether 30%) leading to bromo ester II-30 with its regioisomer in a ~2:1 ratio. Recrystallization of the mixture was done by dissolving the material in pure DCM at room temperature, followed by slow addition of diethyl ether to a final 3:1 ratio in volume. The crystals formed after overnight standing at room temperature was collected and washed with cold diethyl ether to afford II-30 (938 mg, 52%). 1H NMR (500 MHz, Chloroform-d): δ 7.52 (d, J = 5.4 Hz, 1H), 7.19 (d, J = 5.4 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, Chloroform-d): δ 161.12, 138.25, 136.43, 128.62, 124.04, 121.43, 118.57, 61.48, 14.27. II-5-3-3 Synthesis of compound II-33 OMe n-BuLi (2.5 equiv) Me3Sn S OMe S Me3SnCl (3 equiv) S THF MeO -78 °C to r.t., 54% S SnMe3 MeO II-33 II-32 Following the reported procedure30 compound II-32 (1 g, 5 mmol) was dissolved in dry THF (100 mL) and n-BuLi (2.5 M in hexane, 5 mL, 12.5 mmol) was added dropwise 160 at -78 °C under argon balloon. The mixture stirred for 1 hour at this temperature and then, warmed up to room temperature and stirred for additional 2 hours. The reaction brought to -78 °C before adding trimethyltin chloride (1 M in THF, 15 mL, 15 mmol). The solution was brought to the room temperature and stirred 16 hours. After completion, the mixture was poured into water (100 mL) and extracted with petroleum ether (3 × 100 mL). The combined organic layers dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude washed with cold methanol to give compound II-33 as gray product (1.41 g, 54%) 1H NMR (500 MHz, Chloroform-d): δ 3.98 (s, 6H), 0.38 (s, 18H). 13C NMR (126 MHz, Chloroform-d): δ 155.25, 136.09, 118.04, 59.58, 8.25. II-5-3-4 Synthesis of compound II-34 CO2Et OMe Me3Sn S II-30 (2.5 equiv) OMe Pd(PPh3)4 (10 mol%) S S S MeO Toluene/DMF S S S S SnMe3 110 °C, 61% MeO EtO2C II-33 II-34 Following the reported procedure30 to a solution of II-33 (736 mg, 1.4 mmol) and II-30 (1.01 g, 3.5 mmol) in a mixture solvents of toluene (50 mL) and DMF (3.8 mL) was added Pd(PPh3)4 (162 mg, 0.14 mmol) under argon balloon. The reaction stirred at reflux for 48 hours and monitored by TLC. After the completion, the solution concentrated under reduced pressure. The crude product was then purified by column chromatography (silica, chloroform) leading to the pure product II-34 as a yellow solid (530 mg, 61%). 161 1H NMR (500 MHz, Chloroform-d) δ 7.50 (d, J = 5.3 Hz, 2H), 7.27 (d, J = 5.3 Hz, 2H), 4.39 (q, J = 7.1 Hz, 4H), 4.03 (s, 6H), 1.36 (t, J = 7.1 Hz, 6H). 13C NMR (126 MHz, Chloroform-d) δ 161.90, 148.30, 141.28, 140.09, 137.35, 129.31, 128.28, 123.41, 118.91, 114.77, 61.15, 59.49, 14.23. II-5-3-5 Synthesis of compound II-35 CO2Et OMe CO2Et OH S S S BBr3 (6 equiv) S S S S S S DCM, r.t., 100% S S S MeO EtO2C HO EtO2C II-34 II-35 Following the reported procedure30 In a flame dried flask, compound II-34 (397 mg, 0.64 mmol) was dissolved in dry DCM (80 mL) and BBr3 (1.75 M in DCM, 2.2 mL, 3.84 mmol) was added dropwise at room temperature under argon balloon. The reaction stirred for 2.5 hours and monitored by TLC. After completion, the solution was poured into methanol. A yellow precipitate was formed, filtered and dried to give compound II-35 as a yellow solid (380 mg, 100%). 1H NMR (500 MHz, DMSO-d6) δ 10.78 (s, 2H), 7.77 (d, J = 5.3 Hz, 2H), 7.48 (d, J = 5.3 Hz, 2H), 4.27 (q, J = 7.1 Hz, 4H), 1.24 (t, J = 7.1 Hz, 6H). 13C NMR (126 MHz, DMSO-d6) δ 166.78, 151.15, 147.27, 144.55, 141.70, 135.01, 133.02, 127.09, 125.09, 114.64, 65.93, 19.17. 162 II-5-3-6 Synthesis of compound II-36 O CO2Et OH O S S S p-TsOH (1.2 equiv) S S S S S S Toluene, 110 °C, 54% S S S HO EtO2C O II-35 O II-36 Following the reported procedure30 p-toluenesulfonic acid (133 mg, 0.7 mmol) was added in one portion to a suspension of di-ester II-35 (380 mg, 0.64 mmol) in toluene (20 mL) at room temperature. The reaction heated to 110 °C and stirred for 1 hour. After that, the reaction solution was poured into methanol and the precipitate was filtered and dried to give product II-36 as a dark red solid (173 mg, 54%). The analytical date didn’t provided because of low solubility in solvents. II-5-3-7 Synthesis of compound II-38 O 1. 4-(n-C6H13)-C6H4MgBr Ar Ar O (10 equiv) O S S S THF, r.t. to 60 °C S S S S S S 2. p-TsOH (2 equiv) S S S O Toluene, r.t. O O Ar = 4-(n-C6H13)-C6H4 Ar Ar II-36 II-38 Following the reported procedure30 In a flame dried flask, compound II-36 (173 mg, 0.34 mmol) was suspended in dry THF (8 mL) under argon balloon. Then, 4-(n-C6H13)- C6H4MgBr (3.4 mL, 1M in THF, 3.4 mmol) was added dropwise at room temperature. The reaction heated at 60 °C and stirred for 12 hours. After completion, the solution cooled to the room temperature and was poured into ice water. The reaction was extracted with 163 DCM (3 x 15 mL). The combined organic layers dried with anhydrous Na2SO4 and concentrated under reduced pressure to give the tetra-hydroxy compound II-37 which used in the next step without furthered purification. Crude compound II-37 was dissolved in toluene (10 mL) and p-toluenesulfonic acid (129 mg, 0.68 mmol) was added in one portion. After stirring for 2 hours, the mixture was poured into methanol and formed a precipitate. The crude product was then purified by column chromatography (silica, chloroform) leading to the pure product II-38 as a dark yellow solid (306 mg, 81%). 1H NMR (500 MHz, Chloroform-d) δ 7.23 (d, J = 8.2 Hz, 8H), 7.18 (d, J = 5.3 Hz, 2H), 7.12 (d, J = 8.2 Hz, 8H), 7.10 (d, J = 5.3 Hz, 2H), 2.59 (t, J = 7.7 Hz, 9H), 1.62 – 1.58 (m, 8H), 1.33 – 1.26 (m, 24H), 0.88 (t, J = 6.5 Hz, 12H). 13C NMR (126 MHz, Chloroform-d) δ 143.79, 143.46, 139.76, 139.20, 135.14, 131.92, 128.27, 128.10, 126.82, 125.51, 124.71, 119.17, 114.45, 88.61, 35.65, 31.70, 31.23, 29.01, 22.61, 14.10. II-5-3-8 Synthesis of compound II-39 Ar Ar Ar Ar O n-BuLi (3 equiv) O S S S DMF (10 equiv) O S S S S S S THF S S S -78 °C to -50 °C O O O Ar 52% Ar Ar Ar II-38 II-39 Following the reported procedure30 compound II-38 (275 mg, 0.24 mmol) was placed in dry THF (50 mL) at -78 °C under argon balloon and n-BuLi (0.3 mL, 2.5 M, 0.72 164 mmol) was added dropwise. The reaction warmed up to -50 °C and kept for 2 hours at this temperature and then, DMF (185 µL, 2.4 mmol) was added slowly. After stirring for additional 1 hour, the reaction mixture quenched by addition of water. The reaction was extracted with DCM (3 x 70 mL). The combined organic layers dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was then purified by column chromatography (silica, DCM/petroleum ether 30%) leading to the pure product I-39 as a red solid (145 mg, 52%). 1H NMR (500 MHz, Chloroform-d) δ 9.80 (s, 2H), 7.82 (s, 2H), 7.21 (d, J = 8.3 Hz, 8H), 7.15 (d, J = 8.3 Hz, 8H), 2.61 (t, J = 7.8 Hz, 8H), 1.64 – 1.57 (m, 8H), 1.37 – 127 (m, 24H), 0.91 – 0.86 (t, J = 6.2 Hz, 12H). 13C NMR (126 MHz, Chloroform-d) δ 182.64, 146.36, 145.37, 144.13, 144.07, 138.21, 138.12, 135.03, 128.76, 128.38, 128.13, 126.96, 124.85, 115.11, 88.91, 35.66, 31.69, 31.15, 29.05, 22.59, 14.11. 165 II-5-3-9 Synthesis of COi8DFIC O F Ar Ar O O S S S F NC II-40 CN (5 equiv) S S S O O Ar DCM, 45 °C II-39 Ar 90% F F Ar NC Ar O S O S CN S S NC S O S O Ar CN Ar F COi8DFIC F Following the reported procedure30 In a flame dried flask, compound II-39 (80 mg, 0.068 mmol) was dissolved in dry DCM (20 mL) under argon balloon and compound II- 40 (78.2 mg, 0.34 mmol) and pyridine (0.5 mL) was added at room temperature and the reaction refluxed for 3 hours. The solvent removed under reduced pressure and the crude product was then purified by column chromatography (silica, chloroform) leading to the pure product COi8DFIC as a black solid (98 mg, 91%). 1H NMR (500 MHz, Chloroform-d) δ 8.66 (s, 2H), 8.49 (dd, J = 9.9, 6.4 Hz, 2H), 7.98 (s, 2H), 7.56 (t, J = 7.5 Hz, 2H), 7.27 (d, J = 8.3 Hz, 8H), 7.22 (d, J = 8.3 Hz, 8H), 2.64 (t, J = 7.8 Hz, 8H), 1.67 – 1.58 (m, 8H), 1.32 – 1.21 (m, 24H), 0.85 (t, J = 7.2 Hz, 12H). 13C NMR (126 MHz, cdcl3) δ 185.17, 158.22, 155.42, 155.30, 153.96, 153.33, 153.21, 146.76, 144.43, 141.59, 137.87, 137.64, 137.21, 136.52, 136.46, 135.86, 134.40, 134.32, 166 128.58, 128.22, 128.06, 125.73, 121.48, 116.76, 114.91, 114.74, 114.37, 114.22, 112.50, 112.36, 89.27, 69.32, 35.73, 31.77, 31.31, 29.10, 22.62, 14.09. II-5-4 Computational Supplementary Figure II-24. Scatter plot of the experimental spectral energy maxima as a function of the DFT-optimized bond length alternation coordinate (in angstrom). Absorption and emission energies are shown by blue and red dots, respectively 167 Table II-9. Absolute energies of optimized geometries on the DFT level of theory (CAM- B3LYP/6-31G*) S1-S0 Dye Conformers Geometries S0 Energy / a.u. S1 Energy / a.u. Gap / a.u. Franck-Condon point -1809.801264 -1809.710549 0.090715 1 - S1 minimum -1809.800022 -1809.711759 0.088263 Franck-Condon point -1484.092954 -1483.994624 0.098330 Bis-dipole S1 minimum -1484.088437 -1483.998166 0.090271 2 Franck-Condon point -1484.098962 -1484.002956 0.096006 Cyanine-like S1 minimum -1484.073807 -1484.010546 0.066895 Franck-Condon point -1523.376682 -1523.280279 0.096404 Bis-dipole S1 minimum -1523.355859 -1523.287972 0.067887 3 Franck-Condon point -1523.388981 -1523.293277 0.095704 Cyanine-like S1 minimum -1523.386699 -1523.295906 0.090793 Franck-Condon point -1522.160161 -1522.066705 0.093456 Bis-dipole S1 minimum -1522.158405 -1522.068372 0.090032 4 Franck-Condon point -1522.144393 -1522.053229 0.091164 Cyanine-like S1 minimum -1522.143264 -1522.054359 0.088905 Franck-Condon point -1522.167762 -1522.069148 0.098614 Bis-dipole S1 minimum -1522.164092 -1522.072413 0.091678 5 Franck-Condon point -1522.15922 -1522.06249 0.096730 Cyanine-like S1 minimum -1522.156756 -1522.065402 0.091353 Franck-Condon point -1562.663326 -1562.567549 0.095776 Bis-dipole S1 minimum -1562.638213 -1562.577772 0.060441 6 Franck-Condon point -1562.679046 -1562.583593 0.095453 Cyanine-like S1 minimum -1562.676662 -1562.586636 0.090026 168 Table II-9 (cont’d) Franck-Condon point -1561.475774 -1561.377488 0.098285 Bis-dipole S1 minimum -1561.467923 -1561.382244 0.085679 7 Franck-Condon point -1561.476323 -1561.383757 0.092565 Cyanine-like S1 minimum -1561.474749 -1561.385506 0.089244 Franck-Condon point -1600.75445 -1600.657514 0.096936 Bis-dipole S1 minimum -1600.735358 -1600.666551 0.068807 8 Franck-Condon point -1600.764007 -1600.667421 0.096586 Cyanine-like S1 minimum -1600.761831 -1600.671054 0.090777 Table II-10. Important geometric parameters for CAM-B3LYP/6-31G* structuresa Dye Stateb BLA (Å)c Pyr. Ang. (°)d 2 GS 0.03912 0.002 ES 0.03187 0.001 3 GS 0.03910 0.014 ES 0.03066 0.177 4 GS 0.03622 43.354 ES 0.02284 49.371 5 GS 0.05677 7.156 ES 0.04358 15.927 6 GS 0.03948 0.002 ES 0.03046 0.162 7 GS 0.06949 2.115 ES 0.02820 0.1421 8 GS 0.04259 0.011 ES 0.03044 0.002 [a] Geometric parameters are computed at the TD-CAM-B3LYP/6-31G* level. [b] Ground and excited state structures are abbreviated GS and ES, respectively. [c] BLA is defined: 169 BLA = ( r2-3 + r4-5 + r5-6 + r7-8 ) - ( r1-2 + r3-4 + r6-7 + r8-9 ) where rm- n is the distance between carbon atoms m and n of the heptamethine chain. [d] Pyramidalization angle is defined: ( Pyr. Ang. = 360 - qCa - N -Cb + qCa - N -Cc + qCb - N -Cc ) where q Cm - N -Cn is the angle formed by carbon atom m, the amine nitrogen atom, and carbon atom n. Carbon atoms a, b, and c are the three atoms bound to the amine nitrogen. Optimized Geometries (In Angstrom) (CAM-B3LYP/6-31G*) Dye II-6 H -0.5058554220 0.1762746719 -3.4647046816 Franck-Condon point C 0.8274638321 -1.9281220617 -2.1372975518 H -1.8122047363 7.8617759991 -4.0734638064 H 1.5401348873 -2.7572357300 -2.1432805184 C -1.8885658517 7.7571257269 -2.9973907038 H -0.1072651408 -2.3153014421 -2.5655569153 C -2.0977123043 7.5195855010 -0.1943131131 C 1.3637691501 -0.7991433504 -3.0070891423 C -1.5805410273 6.5780285207 -2.3396678174 H 2.3592303343 -0.5105714808 -2.6511314735 C -2.3097886635 8.8313210674 -2.2157363357 H 1.4771424668 -1.1375048655 -4.0408753162 C -2.4145080632 8.7186427030 -0.8326841532 H 1.5758340317 -8.7045217548 1.8190082965 C -1.6790260316 6.4475976258 -0.9601939778 C 1.4527127162 -7.9816488751 2.6171381168 H -2.5590540209 9.7698981915 -2.6989994384 C 1.1494634786 -6.1236986440 4.7177388518 H -2.7445781100 9.5695668987 -0.2469190732 C 1.2446640308 -6.6340116734 2.3756319053 H -2.1801280010 7.4365187621 0.8852505761 C 1.5055398628 -8.3895241746 3.9487167137 N -1.1359439550 5.3464790509 -2.8765985895 C 1.3557432969 -7.4765064793 4.9881711833 C -0.9387562285 4.4246386930 -1.9133545507 C 1.0967381914 -5.7080187554 3.4004053067 C -1.2744680110 5.0457991120 -0.5529266509 H 1.6677492483 -9.4382214228 4.1735790517 H -1.1551375073 6.0086721239 -4.8500764667 H 1.4014334988 -7.8190314629 6.0161303798 C -0.9174701179 5.1068385910 -4.2909018971 H 1.0344842690 -5.4151223072 5.5325471140 H 0.1276003042 4.8444456937 -4.4778789502 C 0.8863612996 -4.3284344901 2.8109007433 H -1.5610139722 4.2968443002 -4.6450756158 C 0.9583644703 -4.6308128373 1.3099608594 C -0.5017049820 3.1374727919 -2.2094924200 C 0.8727221603 -3.7566275751 0.2315561753 H -0.3360393304 2.9025363361 -3.2531726356 H 0.9806089092 -4.1831337698 -0.7575574117 C -0.2798926230 2.1399929468 -1.2605499057 N 1.1449076117 -5.9547676222 1.1385293714 H -0.4665483542 2.3886580210 -0.2264750225 Cl 0.0120114314 0.4141819222 1.1538988063 C 0.1454077917 0.8390089862 -1.5253280819 C 1.2437514955 -6.6043483577 -0.1550247418 C 0.2794583552 -0.1178267988 -0.5026038540 H 2.1508599693 -6.2900184855 -0.6798795186 C 0.5903489564 -1.4743302652 -0.7115233929 H 0.3713736927 -6.3607615168 -0.7665754440 C 0.6536917349 -2.3836175520 0.3427695877 H 1.2751958137 -7.6824307864 -0.0149812576 H 0.5043600367 -1.9852434443 1.3352902400 C -2.4578987655 4.3284773985 0.1237101245 C 0.4363151090 0.4064599149 -2.9482137777 H -2.2025001414 3.3121237346 0.4306222355 H 0.8922958286 1.2384331164 -3.4929264928 H -3.3221027256 4.2792217449 -0.5437393294 170 H -2.7545389226 4.8839698407 1.0176428033 C 1.6027491931 -8.4435386555 3.9019884434 C -0.0438630977 5.0971373052 0.3724897326 C 1.4594250338 -7.5425672459 4.9573821272 H 0.7984062891 5.5902284603 -0.1195417588 C 1.1406978672 -5.7584722433 3.3973434203 H 0.2760956659 4.1018117033 0.6876470504 H 1.7859037933 -9.4917905491 4.1138613671 H -0.2910738697 5.6703325922 1.2702073256 H 1.5315707359 -7.8964312555 5.9801586427 C -0.4987013169 -3.7899176515 3.2194589581 H 1.1167938018 -5.4920828683 5.5315395721 H -0.5503939565 -3.7226099313 4.3095047813 C 0.8961334508 -4.3756805601 2.8327114093 H -1.2953986228 -4.4597538971 2.8857935991 C 0.9497463554 -4.6550051288 1.3313256540 H -0.6926494535 -2.7950278773 2.8128676601 C 0.8382922812 -3.7697383551 0.2662583029 C 2.0130656832 -3.3790876646 3.2597204089 H 0.9400264854 -4.1871259063 -0.7284633812 H 2.9911838790 -3.7504596551 2.9433988209 N 1.1537932546 -5.9894019185 1.1384975327 H 2.0155832364 -3.3124722575 4.3510355982 Cl -0.0684044162 0.4126970597 1.1854427190 H 1.8832463071 -2.3702311327 2.8623844067 C 1.2334987925 -6.6182348829 -0.1643407009 S1 minimum H 2.1215136949 -6.2787607268 -0.7077420939 H -1.7241524533 7.8930069682 -4.1316849236 H 0.3428397738 -6.3811331555 -0.7532101028 C -1.8260832499 7.7949377547 -3.0571133251 H 1.2886490736 -7.6978361355 -0.0433265298 C -2.1029990560 7.5739591453 -0.2543158667 C -2.5104927074 4.3927952959 0.0873717461 C -1.5445436713 6.6086944850 -2.3861205184 H -2.2744222423 3.3726702553 0.3970955130 C -2.2518489680 8.8749753254 -2.2921565627 H -3.3637699928 4.3561344407 -0.5945885533 C -2.3906397709 8.7726115231 -0.9079041561 H -2.8128869295 4.9521698583 0.9772567524 C -1.6792274520 6.4917050975 -1.0008073740 C -0.0971289943 5.1341926226 0.3905908313 H -2.4793540858 9.8142764470 -2.7852696682 H 0.7627859309 5.6192217414 -0.0780556902 H -2.7244412866 9.6316545439 -0.3358828787 H 0.2050981685 4.1358413974 0.7133761356 H -2.2117474073 7.4987183821 0.8234939032 H -0.3647665304 5.7084017766 1.2820895302 N -1.1054072088 5.3843068006 -2.8984719857 C -0.4923947328 -3.8660635922 3.2744820293 C -0.9413415946 4.4562093194 -1.9140516424 H -0.5224269534 -3.8011437447 4.3657582562 C -1.3024613236 5.0904276637 -0.5715751863 H -1.2826200326 -4.5501261224 2.9549363730 H -1.0517800776 6.0316862379 -4.8765022882 H -0.7132935131 -2.8743323284 2.8734518010 C -0.8525848635 5.1297153301 -4.3024375016 C 2.0076547691 -3.4067169122 3.2847932551 H 0.1913878298 4.8401872717 -4.4572698724 H 2.9908702025 -3.7542081746 2.9578437105 H -1.5030233524 4.3302340316 -4.6704664546 H 2.0154437800 -3.3479934562 4.3767681087 C -0.5136058327 3.1624174296 -2.1900467168 H 1.8530012353 -2.3980600949 2.8962004464 H -0.3288967220 2.9201599333 -3.2298873522 C -0.3197106793 2.1589897674 -1.2319493192 Dye II-10 H -0.5196159596 2.4083152150 -0.2007049485 Bis-dipole Franck-Condon point C 0.0966863475 0.8482053819 -1.4921153764 H 6.3215188475 5.2264514052 2.1358302896 C 0.2203687965 -0.1151037525 -0.4650101192 C 6.1269240781 4.3127500461 2.6858437135 C 0.5350985785 -1.4791998609 -0.6712131395 C 5.6481488793 1.9475159330 4.1400563841 C 0.6035534205 -2.3927176160 0.3852771127 C 4.9542238981 3.5916666244 2.5321672990 H 0.4503401196 -1.9981098223 1.3786186673 C 7.0686429214 3.8231802533 3.5901424000 C 0.3973315399 0.4092694466 -2.9081701072 C 6.8378971539 2.6568304957 4.3115582237 H 0.8494602025 1.2382766894 -3.4599477924 C 4.7084307916 2.4236246717 3.2458439196 H -0.5445845793 0.1702478955 -3.4227719088 H 7.9958032916 4.3683442955 3.7323458773 C 0.7763829264 -1.9256021368 -2.0957294985 H 7.5850434739 2.2976902929 5.0106645933 H 1.4769579096 -2.7644348934 -2.1066405211 H 5.4697101027 1.0371917864 4.7051846563 H -0.1638342362 -2.2956809243 -2.5291760769 N 3.8486140666 3.8574264656 1.7000103461 C 1.3246374855 -0.7971955320 -2.9593686595 C 2.8700943747 2.9211343375 1.8484456025 H 2.3183915629 -0.5116069223 -2.5966035916 C 3.3501037935 1.8707404110 2.8596199716 H 1.4425301115 -1.1358833387 -3.9925776808 H 4.6868880383 5.5382607524 0.8066374368 H 1.6371710632 -8.7379443644 1.7713074575 C 3.7489759976 4.9867668484 0.8024484355 C 1.5177820321 -8.0251180489 2.5789972098 H 3.5533467437 4.6461386758 -0.2190520522 C 1.2266384319 -6.1898442552 4.7067251560 H 2.9439288453 5.6619464684 1.1106797833 C 1.2832808435 -6.6724250524 2.3507318899 C 1.6830060082 2.9938809261 1.1605693252 171 H 1.5484799781 3.8397382323 0.4986545677 H 2.3125016016 2.7792075235 4.5539871532 C 0.6130511729 2.0647857587 1.2445386823 H 2.8895242416 1.1324792229 4.8418232955 H 0.7545608521 1.2119530056 1.8954050845 C 3.5130845349 0.4890972641 2.1999459214 C -0.5394581445 2.1320713466 0.5059629066 H 4.1687145231 0.5480041277 1.3275681592 C -1.5224544028 1.0588295908 0.5172710949 H 2.5555626630 0.0719361146 1.8778855322 C -2.0283064989 0.6538850000 -0.7858666546 H 3.9626554266 -0.2071867880 2.9135717077 C -2.1337696566 -0.6661759609 -1.1389490185 H -2.3292483128 0.8298112021 3.6692245379 H -1.8958576847 -1.4150077323 -0.3949327601 H -3.5737903434 -0.3907413097 2.5951343671 C -0.7223370154 3.2292361447 -0.5259077088 Bis-dipole S1 minimum H 0.0827933283 3.1810717003 -1.2722333782 H 6.2944724021 5.2700623033 2.1738075222 H -0.6240377296 4.2021997322 -0.0302970623 C 6.1159697783 4.3449909334 2.7097477896 C -2.2196011665 1.7412271147 -1.8261153981 C 5.6809946465 1.9436900340 4.1263940721 H -1.4955150932 1.6137252512 -2.6430152198 C 4.9489631451 3.6067236002 2.5499563118 H -3.2127908390 1.6290215187 -2.2765976841 C 7.0674585898 3.8550344990 3.5990521876 C -2.0674735268 3.1318115977 -1.2291149152 C 6.8595781457 2.6702952739 4.3020482201 H -2.1469717956 3.8937491290 -2.0088085038 C 4.7270369559 2.4185210046 3.2478866723 H -2.8775068505 3.3216225170 -0.5139709873 H 7.9874803581 4.4108962050 3.7457530566 H -3.3141529468 -4.5092885177 -6.3566313334 H 7.6175654992 2.3112952746 4.9896047000 C -3.0610030773 -4.9628087878 -5.4051925557 H 5.5217270798 1.0203958240 4.6757287419 C -2.4095736757 -6.1770295345 -2.9475415726 N 3.8412265205 3.8673581456 1.7375857120 C -2.7961652364 -4.2107803283 -4.2724655018 C 2.8792513357 2.9018284268 1.8704704128 C -2.9937929818 -6.3505866767 -5.2855427082 C 3.3783455557 1.8484001071 2.8605876884 C -2.6732464333 -6.9557245063 -4.0752128776 H 4.6279695639 5.6074657642 0.9117437325 C -2.4733758141 -4.8008281260 -3.0552623514 C 3.7181550208 5.0132102830 0.8637192406 H -3.1993080818 -6.9651415074 -6.1556623327 H 3.5685964175 4.6910939639 -0.1718063269 H -2.6287691375 -8.0372477398 -4.0074773609 H 2.8732985834 5.6419105456 1.1639390162 H -2.1598696571 -6.6517475750 -2.0029487630 C 1.6903028115 2.9590635877 1.1736690867 C -2.2370934370 -3.7219056130 -2.0162456894 H 1.5450007948 3.8198111841 0.5318619846 C -2.4932474604 -2.4493495848 -2.8352614130 C 0.6405629208 2.0074368296 1.2063559355 C -2.4497027580 -1.1339522930 -2.4411741920 H 0.7662675307 1.1326004042 1.8318516237 H -2.6740125141 -0.3867533100 -3.1916146488 C -0.5289922578 2.1133096296 0.4748553140 N -2.7955859667 -2.8106208773 -4.1136429689 C -1.5761216493 1.1090073508 0.5213241513 N -1.9274524637 0.4726691006 1.6558644866 C -1.9918855208 0.6588668658 -0.7951063673 C -1.4848551160 0.9032436024 2.9822399895 C -2.0561722059 -0.6807338324 -1.1343076607 C -2.9665741377 -0.5561501123 1.7041261233 H -1.7873457226 -1.4048723601 -0.3749789816 H -3.6023906478 -0.4935225088 0.8237057186 C -0.7026193655 3.2245845651 -0.5422291651 H -2.5373485092 -1.5611841516 1.7686316615 H 0.1144685821 3.1904070001 -1.2761281288 H -1.1425072106 1.9352108877 2.9499542564 H -0.6177252757 4.1943457865 -0.0359407534 H -0.6806665694 0.2674224255 3.3659974103 C -2.2057661612 1.7323639370 -1.8435466018 C -3.0797554117 -1.8628860803 -5.1683426102 H -1.4993896670 1.5917301524 -2.6735890103 H -2.2337505338 -1.1830320633 -5.3107272104 H -3.2086891674 1.6211510530 -2.2746373751 H -3.9714878804 -1.2734453146 -4.9317505492 C -2.0413558183 3.1297129207 -1.2614419011 H -3.2542690222 -2.3967960613 -6.1000179403 H -2.1040393383 3.8825158953 -2.0518452081 C -0.7846582708 -3.7898074986 -1.5109326697 H -2.8550742037 3.3348783475 -0.5565518198 H -0.0782838078 -3.6795224159 -2.3374733078 H -3.3653181364 -4.4946063491 -6.3577917813 H -0.6052433715 -4.7615694186 -1.0422796804 C -3.0902335136 -4.9576037353 -5.4171315638 H -0.5677217574 -3.0142346887 -0.7720212631 C -2.3837605445 -6.1971547799 -2.9824869073 C -3.2403691337 -3.8751764339 -0.8600061976 C -2.8061775901 -4.2143868300 -4.2772229871 H -3.1004093136 -4.8480321425 -0.3805460626 C -3.0133887492 -6.3431831644 -5.3141212270 H -4.2697913759 -3.8234138254 -1.2234872705 C -2.6653642312 -6.9620075113 -4.1154290450 H -3.1097947914 -3.1032088409 -0.0975863704 C -2.4561961114 -4.8207673062 -3.0698052354 C 2.4395273569 1.7946574543 4.0968085643 H -3.2312528780 -6.9496361739 -6.1869791819 H 1.4500405630 1.4006210534 3.8537393142 H -2.6137669246 -8.0440505651 -4.0626508143 172 H -2.1132967775 -6.6825961504 -2.0492823849 C 3.2464804299 0.0600079245 -2.0724514297 C -2.2064414034 -3.7557824937 -2.0221464206 H 3.0756938026 -0.5655453879 -2.9395131120 C -2.4805291429 -2.4797493499 -2.8191056731 C 2.2120324196 0.1413881802 -1.1212948336 C -2.4244964557 -1.1622885345 -2.4149020090 H 2.3960672273 0.7180832264 -0.2241229486 H -2.6795144812 -0.4164233483 -3.1584308599 C 0.9487403591 -0.4021460087 -1.2672166687 N -2.8107485067 -2.8273393918 -4.1017984256 C -0.0312733741 -0.1984542065 -0.2438649364 N -1.9954739498 0.5157664020 1.6787091377 C -1.4223956996 -0.2281738623 -0.5865117230 C -1.5754592741 0.9782354697 2.9921946294 C -2.3835831770 -0.4582513256 0.3776812687 C -3.0747941454 -0.4593876945 1.7107105916 H -2.0209857252 -0.6394338082 1.3816151612 H -3.6406132764 -0.4347191137 0.7815819324 C 0.5682548176 -1.0594573238 -2.5807017850 H -2.7024400092 -1.4791479973 1.8702698711 H 1.1377399934 -1.9877462045 -2.7165667780 H -1.1652607425 1.9845923254 2.9312102890 H 0.8821288091 -0.3932059469 -3.3939710765 H -0.8233624472 0.3166698040 3.4402020808 C -1.7299241805 -0.2133094288 -2.0642021939 C -3.1175832437 -1.8705141571 -5.1422817171 H -2.7949907743 -0.3556624834 -2.2495472765 H -2.2722789839 -1.1930926949 -5.3004550050 H -1.4581663504 0.7502157005 -2.5144867196 H -4.0002057287 -1.2789212332 -4.8776420124 C -0.9275719338 -1.3362233445 -2.7247905860 H -3.3182761276 -2.3961625479 -6.0731531417 H -1.1936609190 -2.2841362891 -2.2447120829 C -0.7457117444 -3.8271664084 -1.5342246608 H -1.1836413135 -1.4314900622 -3.7842734693 H -0.0479510872 -3.7100155228 -2.3671922176 H -8.8601125116 -1.2298646051 1.2478749849 H -0.5616602168 -4.8023835893 -1.0740223819 C -8.1874562275 -1.4041660965 2.0798153031 H -0.5251480280 -3.0569610952 -0.7915062296 C -6.4689079897 -1.8675700564 4.2653949643 C -3.1885677799 -3.9206828030 -0.8470924270 C -6.8147712799 -1.2549007594 1.9693684536 H -3.0267146114 -4.8898034801 -0.3666416814 C -8.6919375792 -1.7948116864 3.3194661145 H -4.2247234481 -3.8841885227 -1.1928878953 C -7.8486346722 -2.0250609270 4.4013737003 H -3.0522257030 -3.1424178121 -0.0923973930 C -5.9584475874 -1.4813073094 3.0405052059 C 2.4666184450 1.7379409591 4.0965692310 H -9.7631091190 -1.9204805225 3.4365383872 H 1.4803650673 1.3461463793 3.8379838774 H -8.2656005876 -2.3285841472 5.3553696145 H 2.3343126284 2.7107832784 4.5767576597 H -5.8122197509 -2.0482254971 5.1114428211 H 2.9177048182 1.0595719194 4.8263981706 C -4.5283696000 -1.2285535756 2.6072794284 C 3.5619789022 0.4738453358 2.1857634710 C -4.7194456261 -0.8474745692 1.1335076683 H 4.2183518854 0.5501356938 1.3152690746 C -3.7783057430 -0.5193966017 0.1792784700 H 2.6095808086 0.0489161538 1.8600947501 H -4.1516356701 -0.2844805431 -0.8090251908 H 4.0193445677 -0.2230073348 2.8942785740 N -6.0469018271 -0.8751314570 0.8481113998 H -2.4424303045 0.9966556558 3.6576259708 N 0.3684279600 0.0530629951 1.0458984945 H -3.7499567241 -0.2164932098 2.5355081436 C 1.4689163581 -0.6451679652 1.6929493439 Cyanine-like Franck-Condon point H 1.1008963868 -1.1106851585 2.6157992688 H 7.8399089996 1.0278848789 -4.4058463663 H 2.2812702991 0.0374820038 1.9703441738 C 7.6869688737 1.5416551392 -3.4637916045 C -0.2558424258 1.0508357797 1.9008757159 C 7.3239505095 2.8913625955 -1.0157629315 H -0.7126102020 0.6008008875 2.7905771657 C 6.5322419732 1.3904069421 -2.7142348293 H -1.0140682186 1.6034137501 1.3496287685 C 8.6697853026 2.3929924040 -2.9609109413 H 1.8628751851 -1.4217816528 1.0406041243 C 8.4957938634 3.0617104887 -1.7536791329 H 0.5118777826 1.7543017555 2.2473177485 C 6.3423353640 2.0508671574 -1.5061946335 C -6.6002442164 -0.5585262264 -0.4519335895 H 9.5854390807 2.5328272539 -3.5255669212 H -6.2300143875 -1.2556281632 -1.2100101420 H 9.2754177071 3.7184468904 -1.3836024409 H -6.3326128217 0.4609916853 -0.7450690605 H 7.1915032763 3.4138980614 -0.0729351548 H -7.6846346704 -0.6334951240 -0.4120742630 N 5.3902017048 0.6049292118 -2.9847304591 C 4.1082913911 2.9237004799 -0.7744188655 C 4.4574066214 0.7232998580 -2.0087365980 H 3.1219281770 2.6799426858 -0.3738683611 C 4.9919631498 1.6739685957 -0.9306460581 H 3.9721058230 3.4315985504 -1.7325794895 H 6.1069609319 -0.1290505191 -4.7954123024 H 4.5879942388 3.6259038901 -0.0867804061 C 5.2252898101 -0.2185257542 -4.1648692185 C 5.1825520191 0.9482858585 0.4142327046 H 5.0995565331 -1.2691152322 -3.8865708182 H 5.8133578050 0.0635704285 0.2966484756 H 4.3515789202 0.1035736100 -4.7396118049 H 4.2302969227 0.6343664433 0.8474003026 173 H 5.6725627685 1.6197148063 1.1248150227 H -8.0593660417 -1.7247861624 5.7878047181 C -3.6870855884 -2.5068438106 2.7681215073 H -5.6805711331 -1.1397797525 5.3890611342 H -4.1096775468 -3.3301024821 2.1866193555 C -4.5014562286 -0.9072264716 2.7187540764 H -3.6773889548 -2.8079321353 3.8194772764 C -4.7185590496 -1.0318207434 1.2041868658 H -2.6521943541 -2.3604224133 2.4500717621 C -3.8162610864 -0.9120867718 0.1818907620 C -3.9378364474 -0.0616786254 3.4196572667 H -4.1929922524 -1.0841855428 -0.8185317785 H -3.9298940590 -0.3228463586 4.4816267316 N -6.0405121236 -1.3249034219 0.9800107455 H -4.5378733999 0.8439467139 3.2996203077 N 0.1983686313 0.2978865212 0.7059609227 H -2.9127690856 0.1656068243 3.1201827405 C 0.7411606824 -0.6439628153 1.6487584498 Cyanine-like S1 minimum H 0.0570719091 -1.4946349300 1.7205405601 H 7.8867440429 1.4306295802 -4.3619226738 H 0.9034053898 -0.1846080340 2.6224399401 C 7.7842137971 1.6510528981 -3.3055001663 C 0.0229827944 1.6886651866 1.0328133130 C 7.5596192683 2.2375803184 -0.5605414500 H -1.0476771458 1.9159132927 0.9736179500 C 6.5944444373 1.4589443099 -2.6205787053 H 0.5216086427 2.2871523450 0.2646712702 C 8.8711343874 2.1461934408 -2.5854891377 H 1.6844404696 -1.0250934801 1.2399413632 C 8.7678721672 2.4381738766 -1.2301791680 H 0.4107292995 1.9180803166 2.0239089023 C 6.4765985169 1.7467190080 -1.2636220944 C -6.6111796974 -1.4887548666 -0.3358720135 H 9.8137414783 2.3044653832 -3.0989195307 H -6.2069011103 -2.3759772581 -0.8361693880 H 9.6275933827 2.8221861985 -0.6920409672 H -6.3996461889 -0.6101866579 -0.9533445765 H 7.4794835080 2.4659385098 0.4985762435 H -7.6911221864 -1.5962882804 -0.2539558364 N 5.3630803106 0.9770794774 -3.0949144042 C 4.3856948172 2.7211745336 -0.2948229966 C 4.4221008253 0.9269067718 -2.0970471488 H 3.3543807511 2.5386249750 0.0189538139 C 5.0660435490 1.4367235595 -0.8001117400 H 4.3733663736 3.4880949272 -1.0731465478 H 6.0125542450 0.6840329215 -5.0470177954 H 4.9352874861 3.1198472298 0.5629428366 C 5.1079437583 0.5636403580 -4.4544324634 C 5.0978136466 0.3561204127 0.2936437482 H 4.8075933892 -0.4892091427 -4.4904411184 H 5.5694135702 -0.5587954979 -0.0732574396 H 4.3152750893 1.1707736943 -4.9044416800 H 4.0944398313 0.1032561654 0.6462609357 C 3.1455955579 0.4829365694 -2.3191304838 H 5.6754727068 0.7134365736 1.1511432734 H 2.9052867494 0.1855711575 -3.3321829493 C -3.4724470739 -1.9241271903 3.2393870539 C 2.1041600460 0.3771441031 -1.3536613714 H -3.7408901335 -2.9406525344 2.9417566364 H 2.3510054259 0.7111317669 -0.3535198458 H -3.4368705438 -1.8897318278 4.3322434592 C 0.8300158198 -0.1028864548 -1.5953561684 H -2.4678346809 -1.7148448163 2.8623166950 C -0.1772178526 -0.1576014883 -0.5938955130 C -4.1179888931 0.5269627094 3.1253233881 C -1.5279914485 -0.5744540399 -0.7452652114 H -4.0961797237 0.6085481877 4.2159873999 C -2.4358757314 -0.5803146994 0.2969747836 H -4.8464782049 1.2493838538 2.7487100789 H -2.0941144434 -0.3033896581 1.2872325180 H -3.1311796901 0.8093883297 2.7474994184 C 0.4203591646 -0.5894666796 -2.9684977195 H 1.2750358934 -1.0647820672 -3.4563577662 Dye II-11 H 0.1454375530 0.2725676040 -3.5913634236 Bis-dipole Franck-Condon point C -1.9227925728 -1.0100553349 -2.1390061918 H 0.1920462294 8.4317605281 -1.1078050535 H -2.7077959723 -1.7673688187 -2.0763475969 C 0.5720494048 7.9964559653 -0.1905949021 H -2.3500179821 -0.1577354001 -2.6846297046 C 1.5747010760 6.8994798327 2.2014151804 C -0.7399918125 -1.5775207293 -2.9166101532 C 0.3453891486 6.6725299956 0.1493570626 H -0.4065546052 -2.5057868023 -2.4386666899 C 1.3178745463 8.7713856112 0.6971617382 H -1.0519280112 -1.8368337902 -3.9321963911 C 1.8155104831 8.2362899704 1.8800250590 H -8.7545223417 -2.0027405156 1.5591207356 C 0.8377316179 6.1226363100 1.3284567389 C -8.0779696344 -1.8071576807 2.3832391700 H 1.5100552564 9.8114154828 0.4549518207 C -6.3447813468 -1.3231742308 4.5491473570 H 2.3925946572 8.8590533091 2.5547393279 C -6.7470612519 -1.4759187507 2.1839975395 H 1.9642897817 6.4818034087 3.1254881811 C -8.5323145679 -1.8911595089 3.6990893107 N -0.3638830172 5.6827977382 -0.5548601426 C -7.6827136585 -1.6524081694 4.7733660876 C -0.3600999040 4.4875580421 0.1110024596 C -5.8834250984 -1.2394066828 3.2499251721 C 0.4298103351 4.6641175402 1.4172001170 H -9.5697369533 -2.1511103673 3.8817974079 H -0.8781768090 6.9179315523 -2.1458285163 174 C -1.0132567106 5.8858109670 -1.8291055396 H 1.4227146705 2.7068226130 1.5146061526 H -0.5838778020 5.2290312277 -2.5931694872 H 2.2794909495 4.0163679457 2.3395217453 H -2.0870622010 5.6847455907 -1.7543157255 C 3.1921805171 -2.3761275035 1.8686470760 C -0.9848247217 3.3774699128 -0.3892271325 H 3.9114511771 -2.1418171324 1.0797715912 H -1.4877318775 3.4859248069 -1.3416263665 H 3.7218404486 -2.3505538542 2.8253803278 C -1.0355557380 2.0949263387 0.2352831481 H 2.4338242322 -1.5894855693 1.8822323760 H -0.5614260943 2.0199253799 1.2079656105 C 1.5674642229 -4.1126087557 2.7671598565 C -1.5649690546 0.9500565922 -0.2797057048 H 2.0810155845 -4.1406750740 3.7323000551 C -1.4222861005 -0.3184782174 0.4491315839 H 1.1149956442 -5.0931527017 2.5982431113 C -0.8032913401 -1.4128052238 -0.2866409200 H 0.7649556790 -3.3742473126 2.8367870417 C 0.1623061583 -2.1898518900 0.3000501190 H -2.7507044175 -1.7800264964 3.0287246837 H 0.4189523059 -1.9596491487 1.3268253035 C -4.1307422769 0.4369705616 2.1288401351 C -2.0684565200 0.8153041246 -1.6989021287 H -4.3361219559 0.6199469743 1.0709200920 H -2.0671574713 1.7855773368 -2.1962737617 H -4.6913115553 1.1689925384 2.7161723427 H -3.1095631009 0.4650383315 -1.7032350485 H -4.5065656223 -0.5567573812 2.3873734796 C -1.1670746961 -1.5247492977 -1.7564935110 Bis-dipole S1 minimum H -0.4656043595 -2.1861096166 -2.2665109806 H -0.4532525559 8.5786797297 -1.0704564991 H -2.1554587831 -1.9962220875 -1.8474842580 C 0.1180083780 8.1684684061 -0.2463105941 C -1.1980219689 -0.1747848298 -2.4707864257 C 1.6424716894 7.1234910824 1.8904819167 H -0.1812521655 0.2255960490 -2.5479315155 C 0.0668152499 6.8272897032 0.1050174762 H -1.5772833236 -0.3041587699 -3.4894848526 C 0.9540494412 8.9882635779 0.5050680393 H 4.5248856260 -6.9748976954 -0.9022278732 C 1.7059506410 8.4770200108 1.5611087817 C 4.5352421802 -6.4741292991 0.0590587290 C 0.8165667852 6.2983085393 1.1499973505 C 4.5881680010 -5.1982374667 2.5704980977 H 1.0204303587 10.0423342155 0.2593245141 C 3.6478316715 -5.4586683970 0.3755761381 H 2.3485120888 9.1393467373 2.1307498809 C 5.4621720384 -6.8442380850 1.0328018063 H 2.2333970918 6.7335229580 2.7133880049 C 5.4934321507 -6.2181785362 2.2741011044 N -0.6929361082 5.7885422128 -0.4724475533 C 3.6656331114 -4.8234285938 1.6122904688 C -0.4527172852 4.6042674828 0.1276482441 H 6.1692136251 -7.6370551183 0.8124188778 C 0.5500170447 4.8133705716 1.2634035274 H 6.2240208206 -6.5238043793 3.0149930411 H -1.7703470656 7.0511795549 -1.7279398917 H 4.6142772466 -4.7109995028 3.5409866031 C -1.6116404624 5.9856554875 -1.5809381117 C 2.5758929042 -3.7697414351 1.6560954686 H -1.2069375659 5.5539547096 -2.5003093511 C 1.9562358109 -3.9132178004 0.2581626089 H -2.5747185682 5.5248989088 -1.3536450397 C 0.9158075403 -3.2240524850 -0.3160183330 C -1.0635256978 3.4281088617 -0.3019269808 H 0.6452324610 -3.5046056936 -1.3251377958 H -1.7410642502 3.5060109116 -1.1433015491 N 2.6229194471 -4.8958697551 -0.4107741150 C -0.8717340758 2.1529661314 0.2575939215 N -1.8475648574 -0.4467786493 1.7064891941 H -0.2083210704 2.0576705694 1.1085215263 C -2.6416000711 0.5856624595 2.4172196590 C -1.4990762239 0.9939571199 -0.1566213093 H -2.3111369530 1.5774463984 2.1390802721 C -1.2210034282 -0.3011688339 0.5095357307 C -1.8373720156 -1.7175076431 2.4359143398 C -0.3666715342 -1.1664521797 -0.2166985757 H -0.9850060261 -1.7732312925 3.1191486000 C 0.4107270457 -2.1279807851 0.4062686962 H -1.8021102247 -2.5567937248 1.7450348019 H 0.4682457011 -2.0617397140 1.4873770941 H -2.4304628951 0.4607675122 3.4818457389 C -2.1753479186 0.8173246897 -1.4721063686 C 2.3133402620 -5.2984355792 -1.7649351601 H -2.5275336826 1.7404204024 -1.9417964615 H 2.4135734389 -4.4512496674 -2.4508480279 H -3.0241955577 0.1327989040 -1.3772334788 H 1.2929550383 -5.6894418080 -1.8309333906 C -0.4612436932 -1.1103422935 -1.7400184374 H 3.0034335775 -6.0788990452 -2.0781490010 H 0.5238784542 -1.2728971369 -2.1892936565 C -0.4533071459 4.4424489065 2.6579581046 H -1.0775037898 -1.9638107782 -2.0563404667 H -0.7585849409 3.3981579770 2.7643488327 C -1.0627163765 0.1695143975 -2.3439881812 H -1.3537394252 5.0606262457 2.6150754495 H -0.2745249467 0.9177676140 -2.4799728684 H 0.1021843479 4.7189687059 3.5586334711 H -1.4696156421 -0.0463369645 -3.3368654584 C 1.6801458991 3.7675661471 1.4590519373 H 4.5206067783 -7.1251273994 -0.8832533029 H 2.3023028173 3.9210655849 0.5736788076 C 4.4879734046 -6.6992332237 0.1132092196 175 C 4.4508219831 -5.5971330974 2.7039363311 H -2.1512618813 -3.6641150189 -9.6070480070 C 3.6158175238 -5.6746018218 0.4503108907 H -1.6775437117 -1.2528607769 -9.8355983383 C 5.3475780046 -7.1695128177 1.1056059002 H -1.1415411654 0.1140687677 -7.8365363781 C 5.3355572456 -6.6299029874 2.3867671902 N -1.4927143871 -3.2864422202 -5.0209809218 C 3.5944403075 -5.1232064061 1.7298439727 C -1.1663449335 -2.2310423835 -4.2361346069 H 6.0418998756 -7.9683015674 0.8660605529 C -1.0313359815 -0.9845679304 -5.1196438513 H 6.0177748155 -7.0070074676 3.1407203254 H -1.9760894589 -5.2837226062 -5.3471667033 H 4.4434862345 -5.1741756045 3.7044999223 C -1.7015509728 -4.6302398972 -4.5222140191 C 2.5503961411 -4.0247643797 1.7909539448 H -0.7879868553 -5.0162567535 -4.0595579426 C 2.0300683031 -4.0172854837 0.3479986770 H -2.5079084206 -4.6431797820 -3.7833049730 C 1.1264722528 -3.1713931290 -0.2400618506 C -0.9885172228 -2.3634980052 -2.8716853373 H 0.9536010289 -3.3030973819 -1.3031846450 H -1.1087442046 -3.3557035574 -2.4549430569 N 2.6613052045 -5.0254084999 -0.3442886575 C -0.6529071314 -1.3278351999 -1.9800078063 N -1.8489380832 -0.6413597270 1.6975658000 H -0.5981058570 -0.3205734530 -2.3724701834 C -2.4543068791 0.3626628885 2.5598116825 C -0.3270607356 -1.4974951296 -0.6463692796 H -1.7933054939 1.2324541548 2.6066552567 C 0.0187370023 -0.3587836033 0.1474907682 C -2.3293460069 -1.9963348600 1.9382871043 C 0.8471979016 -0.5360398889 1.3037718195 H -2.0111943273 -2.3480127021 2.9258606402 C 0.8274151905 0.3875079052 2.3291079663 H -1.9311411289 -2.6748211506 1.1873285739 H 0.1480349166 1.2217337008 2.2055727973 H -2.4841645401 -0.0585613726 3.5707978246 C -0.1903543239 -2.9019266367 -0.0877179213 C 2.3968602266 -5.3366039608 -1.7273455211 H 0.4174582235 -3.4858099465 -0.7901701731 H 2.7800269086 -4.5572123249 -2.3971531045 H -1.1713923640 -3.3935081163 -0.0606714930 H 1.3196949195 -5.4401416258 -1.8909869741 C 1.5315775139 -1.8760658079 1.4167527753 H 2.8725194173 -6.2818530779 -1.9845585781 H 2.2814444865 -2.0036333788 0.6255470444 C -0.0727283832 4.4878544772 2.6355820375 H 2.0570542121 -1.9747032808 2.3670642510 H -0.2875026236 3.4230716980 2.7439679572 C 0.4619648561 -2.9635415378 1.2936192334 H -1.0002228132 5.0448476928 2.7906432370 H 0.8935728812 -3.9565318392 1.4514179590 H 0.6271127262 4.7729807525 3.4253543849 H -0.2840314147 -2.8101531348 2.0808401879 C 1.8530936020 4.0233207546 1.0356750717 H 3.2219132597 1.6027463397 8.3341318739 H 2.2892079335 4.2538306188 0.0604349234 C 2.4337720742 2.2332131627 7.9388140414 H 1.6963818126 2.9447401322 1.0954218061 C 0.3775487044 3.8861507157 6.9467272032 H 2.5805588329 4.3016885068 1.8027959794 C 1.8927896380 2.0430568889 6.6779328395 C 3.2075462256 -2.6871013993 2.1726877206 C 1.9216646577 3.2795832700 8.7046593880 H 4.0167449179 -2.4411113960 1.4802499531 C 0.9073119997 4.0986629843 8.2201144143 H 3.6327205253 -2.7568656156 3.1785767615 C 0.8772408410 2.8509586445 6.1796518474 H 2.4892326358 -1.8646799306 2.1622691737 H 2.3248642773 3.4528156785 9.6968330645 C 1.4469322250 -4.4093089401 2.7940676086 H 0.5252517638 4.9056511779 8.8356787001 H 1.8813543015 -4.5362296972 3.7900350270 H -0.4158572676 4.5264208367 6.5720674984 H 0.9763851692 -5.3545836482 2.5112563111 C 0.5056946470 2.3932461411 4.7829562335 H 0.6679365984 -3.6458512713 2.8593249000 C 1.4505889743 1.1995672511 4.5934654760 H -3.4251631690 -2.0376251868 1.9008934514 C 1.5695284827 0.3327845348 3.5270960440 C -3.8610105062 0.7985463781 2.1515380613 H 2.2980480167 -0.4614916209 3.6260540390 H -3.8543824717 1.2837245372 1.1708956817 N 2.2200635114 1.0744053940 5.7058401301 H -4.2665043269 1.5078836608 2.8794107771 N -0.4357245103 0.8884999883 -0.2107539562 H -4.5451399896 -0.0528919475 2.1034539423 C 0.3989497102 2.0918338845 -0.1582115458 Cyanine-like Franck-Condon point H -0.0551046996 2.8270635131 0.5199076602 H -2.1005241148 -4.7622497151 -7.3991372083 C -1.8078395211 1.1170270608 -0.6478456973 C -1.8907795622 -3.7019818633 -7.4808085848 H -2.2357284377 1.9317129005 -0.0503550591 C -1.3488160721 -0.9468748815 -7.7319381318 H -2.4005859698 0.2177948590 -0.4896161633 C -1.5880776930 -2.9169382047 -6.3807155187 H 1.3671591172 1.8151492223 0.2560976690 C -1.9176060082 -3.0757053449 -8.7261106551 H -1.8850085714 1.4042077206 -1.7006666506 C -1.6508486131 -1.7167005830 -8.8556635321 C 3.2365967768 0.0576351879 5.8751823804 C -1.3183978156 -1.5582053445 -6.4926317738 H 3.9670742169 0.1086199845 5.0626365994 176 H 2.7897176437 -0.9415729631 5.8902115007 H 2.2195702968 -2.1066173754 0.9424059749 H 3.7573232526 0.2207202211 6.8162004744 H 1.7216487627 -2.1138315440 2.6305504833 C -2.0859470243 0.0809929000 -4.7692871967 C 0.3113796434 -3.0570290884 1.2945119008 H -1.9115796245 0.5214155691 -3.7851677950 H 0.7072536526 -4.0564652097 1.4980595685 H -3.0937187106 -0.3419723010 -4.7824424673 H -0.5505368086 -2.9115793574 1.9548381476 H -2.0484857507 0.8858377074 -5.5085644724 H 3.2191652402 1.6463332489 8.3681307749 C 0.3918581898 -0.4022046741 -5.0686434205 C 2.4530719108 2.2960416596 7.9612410777 H 1.1364053041 -1.1597246487 -5.3264488151 C 0.4495655636 4.0011292695 6.9364482210 H 0.6350879035 -0.0073330767 -4.0795379694 C 1.8840835775 2.0827433485 6.7089344646 H 0.4797924548 0.4150587646 -5.7901357418 C 1.9980514273 3.3867322351 8.6934920089 C 0.8007629770 3.5153538382 3.7707151242 C 1.0089007887 4.2333414302 8.1938936532 H 1.8513944759 3.8141360559 3.8106060746 C 0.8915436710 2.9223335748 6.1963365643 H 0.1916321156 4.3919266691 4.0087637388 H 2.4227553339 3.5789992387 9.6731129031 H 0.5701771173 3.2130126951 2.7468030600 H 0.6720687963 5.0766563540 8.7869201306 C -0.9723039258 1.9688819478 4.7337436276 H -0.3226201108 4.6614518440 6.5526676619 H -1.6055997601 2.8182999203 5.0048418029 C 0.4786076907 2.4366175388 4.8226235748 H -1.1724178117 1.1597880819 5.4407100813 C 1.3693645444 1.2056824785 4.6597798875 H -1.2686019070 1.6326064673 3.7372698977 C 1.4395991407 0.2965465000 3.6208297427 C 0.5979544677 2.7262383099 -1.5326762986 H 2.1373413430 -0.5226931435 3.7452241340 H 1.2747421460 3.5807697203 -1.4445949285 N 2.1523469083 1.0798884015 5.7771819520 H -0.3375751835 3.0929698044 -1.9627704872 N -0.4138307717 0.8451831142 -0.1570546973 H 1.0451576755 2.0110627188 -2.2299502246 C 0.5102319947 1.9736960081 -0.2104355894 Cyanine-like S1 minimum H 0.0476477606 2.8362976153 0.2892233062 H -2.0970446081 -4.6902095948 -7.4782609148 C -1.7733732207 1.1183231943 -0.5881005168 C -1.9021996453 -3.6260813122 -7.5451102684 H -2.1918711274 1.9329434053 0.0178917163 C -1.3854720052 -0.8588300070 -7.7581772764 H -2.3904697771 0.2312568883 -0.4468425432 C -1.5956659749 -2.8533611329 -6.4298393378 H 1.4050127869 1.7146895604 0.3575460660 C -1.9468348277 -2.9817905848 -8.7770282746 H -1.8464600159 1.4225336965 -1.6394494152 C -1.6932037751 -1.6156647824 -8.8895928124 C 3.1263227587 0.0264250502 5.9656844603 C -1.3367970025 -1.4848865904 -6.5278708430 H 3.8498110905 0.0253302116 5.1446984555 H -2.1825661647 -3.5581028278 -9.6654884833 H 2.6364397436 -0.9522878013 6.0082307258 H -1.7349384697 -1.1382159683 -9.8625478033 H 3.6616911574 0.1897905190 6.8983055673 H -1.1875515728 0.2048936526 -7.8502189386 C -2.1045889667 0.1251303952 -4.7736480906 N -1.4872054978 -3.2373196669 -5.0900133043 H -1.9363710906 0.5322028158 -3.7742653267 C -1.1493215210 -2.1834508791 -4.2888999153 H -3.1101520559 -0.3017076038 -4.8059613981 C -1.0419746810 -0.9267371683 -5.1516846738 H -2.0658403312 0.9538259288 -5.4864862180 H -2.0700901405 -5.2065655661 -5.4212701803 C 0.3733692790 -0.3198049775 -5.1049298558 C -1.6914873016 -4.5879389045 -4.6104672367 H 1.1279974939 -1.0608875930 -5.3801300437 H -0.7531453661 -5.0195167960 -4.2458605031 H 0.6152036552 0.0630123933 -4.1111612297 H -2.4243132813 -4.5939809003 -3.7984661582 H 0.4410341779 0.5110386917 -5.8132312727 C -0.9311178750 -2.3395435227 -2.9278107831 C 0.7870635377 3.5160863397 3.7651769199 H -1.0067926177 -3.3484292438 -2.5383924732 H 1.8480259103 3.7783313334 3.7680968181 C -0.6105318512 -1.3246390990 -2.0097442447 H 0.2142298338 4.4206335000 3.9889261626 H -0.5847418988 -0.3012846746 -2.3594772977 H 0.5170013384 3.1872723276 2.7591877842 C -0.2679060446 -1.5383001260 -0.6705250671 C -1.0175227639 2.0666745421 4.8072486737 C 0.0068957715 -0.4364066360 0.1874452654 H -1.6163980320 2.9518708180 5.0404420947 C 0.7173421418 -0.6352124580 1.4221007934 H -1.2404706793 1.3009361502 5.5544094162 C 0.7061610458 0.3368879953 2.4140193668 H -1.3313507283 1.6935775965 3.8296443867 H 0.0641848206 1.1903600922 2.2341339558 C 0.9113533541 2.3611882493 -1.6331406495 C -0.1154677799 -2.9585779392 -0.1670631066 H 1.5981337313 3.2128570774 -1.6123407007 H 0.6343178343 -3.4628485860 -0.7918299216 H 0.0470026708 2.6504826645 -2.2379443620 H -1.0508939863 -3.5115408531 -0.3188751446 H 1.4201589976 1.5296805650 -2.1305704993 C 1.3561731918 -1.9855660070 1.6106145897 177 Dye II-12 C -0.0080782464 0.4022149355 2.4123710734 Bis-dipole Franck-Condon point H 0.8693332215 -0.0086676145 2.9064810809 H -5.9127742892 -5.5544325253 -3.7623788414 C -1.1990167745 -0.4532513386 2.1570410006 C -5.3216751816 -5.8525759240 -2.9040518722 H -1.1275643701 -1.5003291939 2.4479559668 C -3.7981683100 -6.6634609513 -0.6749012102 H -0.1884454670 1.4599785263 2.5969187637 C -4.4814805952 -4.9749303783 -2.2391883162 C -2.5811753943 0.1415805080 2.2317068883 C -5.3877310236 -7.1608561557 -2.4270548777 H -2.5735930547 1.1957074929 1.9414995352 C -4.6385868000 -7.5660617912 -1.3272878752 H -2.9526780599 0.0697127157 3.2580402075 C -3.7243998087 -5.3641534627 -1.1403665206 H -3.2833605386 -0.3828365285 1.5783670803 H -6.0374240386 -7.8720101129 -2.9260896434 C 3.8591394802 5.4351881388 -0.7645687959 H -4.7086424163 -8.5892724504 -0.9748399247 H 2.9031140405 5.9154762267 -0.5343843414 H -3.2149063761 -6.9833548169 0.1837474667 H 3.7809661378 4.9308393666 -1.7322463090 N -4.2266031565 -3.6120317634 -2.5043682255 H 4.6252011481 6.2039033248 -0.8356558788 C -3.3313803084 -3.0897192842 -1.6298359844 C 3.3200289952 2.6444575060 3.0352656900 C -2.9129466155 -4.1852487597 -0.6413875253 H 3.0233737202 3.6548112985 3.3284690017 H -5.4144087179 -2.0134122955 -3.1677006144 H 3.9049060902 2.2144061895 3.8531430596 C -4.8484603839 -2.8577819231 -3.5729873656 H 2.4172114376 2.0426988205 2.9147331624 H -4.0939393900 -2.4798225436 -4.2694395094 C 4.5723330101 1.2434648750 1.3221826690 H -5.5327410809 -3.5022112725 -4.1203484788 H 5.1751423409 0.7811234545 2.1089167541 C -2.9276423416 -1.7702968940 -1.6998983997 H 5.1706967606 1.2646731649 0.4077681824 H -3.3519820658 -1.1712343329 -2.4956820730 H 3.7017665157 0.6074515520 1.1456069685 C -2.0087285105 -1.1477251054 -0.8346736365 C -3.3270790223 -3.8369596036 0.8000112463 H -1.5766405365 -1.7500997762 -0.0466273599 H -4.3940857593 -3.6062857253 0.8575041455 C -1.5596276116 0.1552200347 -0.9430649063 H -2.7697064867 -2.9825103890 1.1909731479 C -0.5594951395 0.6431071972 -0.0450186756 H -3.1321406752 -4.6928739357 1.4520677234 C 0.2089884200 1.8061173050 -0.3622671183 C -1.4088105469 -4.4996092767 -0.7332864025 C 1.4046895046 2.0690708025 0.2826867827 H -0.7912852399 -3.6619177656 -0.4016340132 H 1.7232529198 1.3740629888 1.0469957324 H -1.1231591944 -4.7498711442 -1.7581369521 C -2.0312972889 1.0400630257 -2.0749764256 H -1.1791653124 -5.3608090683 -0.0995829748 H -3.1098413095 0.9093309728 -2.2118349865 Bis-dipole S1 minimum H -1.5625887489 0.7283781504 -3.0192488028 H -5.9181845748 -5.5528385541 -3.7800354623 C -0.2500755328 2.6904155159 -1.5023076818 C -5.3268808417 -5.8591882178 -2.9250003642 H -0.0624859533 3.7373599268 -1.2438208229 C -3.7987232503 -6.6933966382 -0.7027083487 H 0.3447187266 2.4846492828 -2.4036407209 C -4.4732708841 -4.9860690489 -2.2578474185 C -1.7279423490 2.5076809199 -1.8146015366 C -5.4025259500 -7.1653815112 -2.4538572374 H -2.3276447732 2.8615761918 -0.9671143437 C -4.6512760559 -7.5840637253 -1.3565509958 H -2.0089646731 3.1133735690 -2.6806694405 C -3.7130143517 -5.3923742094 -1.1587665705 H 6.3713988573 6.3771234060 0.3446190681 H -6.0601329642 -7.8690475486 -2.9534502172 C 6.3837929446 5.5442554071 1.0381633456 H -4.7308173677 -8.6084597164 -1.0092287096 C 6.4442529977 3.3923458411 2.8588207985 H -3.2145532199 -7.0244365932 0.1508899382 C 5.3825578764 4.5876342441 1.0676521066 N -4.2121316466 -3.6381132196 -2.5125689198 C 7.4297591100 5.4039317673 1.9489762096 C -3.3037459743 -3.1234863012 -1.6284498516 C 7.4647724522 4.3438139795 2.8488316291 C -2.8888172512 -4.2261956574 -0.6549628000 C 5.4012588499 3.5229785128 1.9611417553 H -5.3588585413 -2.0066176140 -3.1618059171 H 8.2279648390 6.1385540190 1.9528320318 C -4.8285312267 -2.8710479869 -3.5736901258 H 8.2894876516 4.2574716683 3.5476205962 H -4.0742007263 -2.5181849601 -4.2845154704 H 6.4739586183 2.5670968492 3.5643164838 H -5.5443475686 -3.4939148340 -4.1053382042 C 4.1691858826 2.6659687540 1.7516934233 C -2.8938001660 -1.8031272995 -1.6915001610 C 3.4655037564 3.4177272757 0.6152945292 H -3.3260697432 -1.1992548407 -2.4808362924 C 2.2694948320 3.1383184505 -0.0182895439 C -1.9700203685 -1.1756477489 -0.8309980957 H 1.9723317730 3.8116901087 -0.8115010550 H -1.5157509773 -1.7694359716 -0.0490430468 N 4.2190418870 4.4919270283 0.2738966074 C -1.5532935886 0.1482250623 -0.9288948664 N -0.2790543391 -0.0923161706 1.0826490789 C -0.5946077513 0.6700589736 -0.0019201607 178 C 0.1907818724 1.8186848181 -0.3283037812 C -1.3848449884 -4.5508513040 -0.7550858929 C 1.4051921556 2.0653965685 0.3090518068 H -0.7645625945 -3.7138982882 -0.4272239101 H 1.7310838254 1.3455924262 1.0466754289 H -1.1059140739 -4.8035000120 -1.7810233968 C -2.0305113510 1.0356082198 -2.0534235735 H -1.1556645883 -5.4117065341 -0.1203755000 H -3.1041073377 0.8860056391 -2.2102110519 Cyanine-like Franck-Condon Point H -1.5410260565 0.7413240178 -2.9935116699 H -6.3804304284 -5.3975243414 -3.6313602336 C -0.2798759031 2.7104820454 -1.4551488142 C -5.8736311388 -5.6590494492 -2.7096826333 H -0.1063228748 3.7582872409 -1.1888249635 C -4.5662620208 -6.3755234511 -0.3153489978 H 0.3208539944 2.5204366504 -2.3565936237 C -4.9330553148 -4.8334362072 -2.1169016052 C -1.7543444499 2.5061751543 -1.7742092461 C -6.1535786137 -6.8669714637 -2.0728981621 H -2.3619651497 2.8381879294 -0.9240788893 C -5.5104141896 -7.2252474613 -0.8921056245 H -2.0445163593 3.1177930255 -2.6333034634 C -4.2819854114 -5.1747526613 -0.9381063878 H 6.3871432187 6.3798043692 0.3056955509 H -6.8862527472 -7.5365266783 -2.5104512502 C 6.4039967853 5.5493225572 1.0018945988 H -5.7440510441 -8.1719029775 -0.4174306991 C 6.4746261267 3.4023614711 2.8337090242 H -4.0665173561 -6.6595523553 0.6060894203 C 5.3924984399 4.5951456940 1.0464888393 N -4.4632233302 -3.5678295596 -2.5399823092 C 7.4573584342 5.4076521221 1.8984916928 C -3.5317027098 -3.0741891028 -1.6985235327 C 7.4988441763 4.3501024556 2.8060416141 C -3.3188092241 -4.0707198549 -0.5537243162 C 5.4203719231 3.5309084962 1.9505489839 H -5.2886910550 -1.8802115991 -3.4693026427 H 8.2601052948 6.1374852473 1.8884706654 C -4.9332985601 -2.8810339973 -3.7280090635 H 8.3316405961 4.2648718437 3.4954767937 H -4.1336635899 -2.7977911376 -4.4697626499 H 6.5105087861 2.5796966275 3.5417063647 H -5.7592375972 -3.4386503155 -4.1637122093 C 4.1885102722 2.6722830460 1.7577795823 C -2.9057481131 -1.8540203354 -1.9273713703 C 3.4712207976 3.4232821955 0.6364912958 H -3.1605707168 -1.3349274101 -2.8430687034 C 2.2582763978 3.1514771865 0.0268010660 C -1.9807154078 -1.2686763113 -1.0626481871 H 1.9385294687 3.8452697779 -0.7413326239 H -1.7143570081 -1.7910920536 -0.1561076218 N 4.2317298328 4.5010812552 0.2754237320 C -1.3397004531 -0.0401809545 -1.2413779583 N -0.3102601559 -0.0763480000 1.1342772925 C -0.3673607146 0.3801937469 -0.3015608820 C -0.1006135875 0.4805847623 2.4558188741 C 0.3322965485 1.6150610405 -0.4736088918 H 0.7566509660 0.0952899834 3.0028326837 C 1.4594182111 1.9679164402 0.2574055694 C -1.2772283778 -0.3869828782 2.1895732283 H 1.7923483947 1.3214241750 1.0505006144 H -1.2185666951 -1.4214055822 2.5255412397 C -1.6724060689 0.8332675294 -2.4264952025 H -0.2913222806 1.5445661567 2.5866241345 H -2.6956038149 0.6396409523 -2.7589872094 C -2.6633905926 0.2040172989 2.1914165125 H -1.0179475260 0.5924723019 -3.2759900362 H -2.6520418220 1.2439869300 1.8537813358 C -0.1150947773 2.5698548042 -1.5671842868 H -3.0692742369 0.1776721632 3.2070032816 H -0.0560075071 3.5960820985 -1.1907418280 H -3.3397552772 -0.3556535567 1.5397468392 H 0.5856153462 2.5125483320 -2.4125883450 C 3.8674500870 5.4336342204 -0.7695224813 C -1.5248441677 2.3027561407 -2.0662715116 H 2.9436720521 5.9631896677 -0.5134829362 H -2.2506127133 2.5578307162 -1.2854552216 H 3.7231795843 4.9068127694 -1.7177852135 H -1.7428720819 2.9385461171 -2.9291960905 H 4.6630513811 6.1640966237 -0.8975252288 H 6.1410100400 6.5763982278 0.5231315403 C 3.3525606008 2.6375582111 3.0518623136 C 6.0978711949 5.8225686212 1.3007471974 H 3.0570947339 3.6448684199 3.3559059381 C 6.0078675542 3.8819987666 3.3435982141 H 3.9449890366 2.1991506259 3.8600663139 C 5.1433928742 4.8189380230 1.3096551997 H 2.4496567149 2.0361212199 2.9301199049 C 7.0200585501 5.8377987626 2.3460337043 C 4.5926696277 1.2478259420 1.3255328646 C 6.9798596463 4.8829533565 3.3568559470 H 5.2026675494 0.7880864812 2.1085560513 C 5.0886868782 3.8576168552 2.3116951310 H 5.1829751509 1.2697342677 0.4060629054 H 7.7798046275 6.6117422123 2.3677564119 H 3.7211464884 0.6109971865 1.1582050601 H 7.7072972973 4.9176188119 4.1604015928 C -3.2817488233 -3.8864879493 0.7965452957 H 5.9778070562 3.1389778027 4.1350594899 H -4.3465368331 -3.6511827810 0.8701221357 C 3.9356893930 2.9116583674 2.0425663689 H -2.7137873668 -3.0361177799 1.1807821190 C 3.3588808584 3.4966390780 0.7470030200 H -3.0792986266 -4.7467771680 1.4409232142 C 2.2565167598 3.1015143197 0.0101177437 179 H 1.9992858105 3.7202130314 -0.8384917437 H -1.7023971008 -1.8062922989 -0.1694074396 N 4.1038005419 4.5705138754 0.3876678385 C -1.3465253596 -0.0436771058 -1.2442239167 N -0.1772398302 -0.5461844318 0.7608273237 C -0.3650407355 0.3848742756 -0.3017917639 C 0.2644739794 -0.2576259934 2.1161842511 C 0.3420057883 1.6152116013 -0.4807767210 H 0.5735533827 0.7472268858 2.3804682178 C 1.4737173601 1.9744310101 0.2598168596 C 1.1010619457 -1.0925956449 1.2149835311 H 1.8010122581 1.3272270660 1.0540470146 H 1.9904928688 -0.6239339841 0.7986523582 C -1.6724560160 0.8326905554 -2.4251389337 H -0.3283007726 -0.7491760144 2.8847592588 H -2.6891811465 0.6366656034 -2.7746600801 C 1.1976006141 -2.5875959400 1.3636488571 H -1.0039803787 0.5980664844 -3.2665306353 H 0.2860061190 -2.9913945037 1.8123158778 C -0.1131534507 2.5683545433 -1.5696160936 H 2.0432807282 -2.8543764677 2.0052664538 H -0.0455489381 3.5964333144 -1.2003484901 H 1.3481264998 -3.0667251716 0.3912088799 H 0.5804726533 2.5016466265 -2.4211273938 C 3.8583571556 5.3673861086 -0.7971393038 C -1.5272408235 2.3016082299 -2.0588705577 H 2.8990772451 5.8892172625 -0.7240741292 H -2.2473977993 2.5523943150 -1.2717212115 H 3.8518806494 4.7315435290 -1.6868077937 H -1.7520299853 2.9396129066 -2.9185533553 H 4.6497685531 6.1054323428 -0.9068524437 H 6.1592293109 6.5976031597 0.5264136847 C 2.9137716363 2.9815661855 3.1908412760 C 6.1156939310 5.8410936571 1.3014114477 H 2.5468368783 4.0013918572 3.3302528871 C 6.0216225112 3.8908391777 3.3416691838 H 3.3867543258 2.6619269952 4.1235545220 C 5.1535234240 4.8358646055 1.3064978413 H 2.0548666264 2.3320167465 3.0078935457 C 7.0359324011 5.8501331655 2.3436563097 C 4.4606576641 1.4773004579 1.8509298631 C 6.9954529861 4.8902643104 3.3544677665 H 5.0015486123 1.1663093419 2.7488724380 C 5.1003407295 3.8691745898 2.3127021581 H 5.1494731458 1.4173544255 1.0045721070 H 7.7979405237 6.6220208556 2.3678373918 H 3.6508982968 0.7627353053 1.6892181638 H 7.7249973174 4.9220283201 4.1563051351 C -3.7122816064 -3.4772047460 0.8126547148 H 5.9914349836 3.1456540018 4.1309830529 H -4.7288759474 -3.0759480021 0.7906135204 C 3.9492663520 2.9235311158 2.0452943652 H -3.0346781170 -2.6801814070 1.1244437708 C 3.3735463992 3.5088467128 0.7551766354 H -3.6790066281 -4.2649682160 1.5704871219 C 2.2701626836 3.1105658579 0.0149912684 C -1.8755549256 -4.6069509645 -0.5389923015 H 2.0157105112 3.7270763031 -0.8378184464 H -1.1546375649 -3.8269214768 -0.2866175188 N 4.1233021412 4.5932805478 0.3953102473 H -1.6023781436 -5.0270068900 -1.5106371301 N -0.1764659344 -0.5365047503 0.7638555796 H -1.7910455766 -5.4023424142 0.2066640906 C 0.2530989957 -0.2510596302 2.1215747366 Cyanine-like S1 minimum H 0.5681664991 0.7522812074 2.3880035459 H -6.3939553743 -5.4193757773 -3.6474783909 C 1.0950566653 -1.0876290159 1.2234171939 C -5.8883785675 -5.6764070661 -2.7239847187 H 1.9907793623 -0.6192039254 0.8186079998 C -4.5796812497 -6.3825681182 -0.3231329633 H -0.3449436949 -0.7392321608 2.8885423685 C -4.9472285384 -4.8397116569 -2.1318531594 C 1.1886431410 -2.5838842060 1.3649809825 C -6.1649072499 -6.8798378422 -2.0846058552 H 0.2699017514 -2.9887057943 1.7983597503 C -5.5227757830 -7.2347603468 -0.8988660770 H 2.0257786238 -2.8579975878 2.0148857760 C -4.2950339781 -5.1831706689 -0.9459374282 H 1.3498451092 -3.0564260272 0.3906832879 H -6.8948490682 -7.5535307203 -2.5211115146 C 3.8772495828 5.3923673265 -0.7870897944 H -5.7574212194 -8.1800363442 -0.4217249239 H 2.9142141361 5.9082613567 -0.7141726685 H -4.0807355741 -6.6633216402 0.5997025333 H 3.8744040537 4.7592275651 -1.6793265379 N -4.4875966281 -3.5882758380 -2.5513659558 H 4.6647699639 6.1352221068 -0.8926025893 C -3.5477860591 -3.0849328685 -1.6994762720 C 2.9285034610 2.9860082071 3.1990419258 C -3.3328775176 -4.0806104105 -0.5599214059 H 2.5636263915 4.0054499603 3.3471836856 H -5.3109706822 -1.9061185626 -3.4930054530 H 3.4033687850 2.6564538734 4.1276687659 C -4.9505489451 -2.9080997167 -3.7432043287 H 2.0687896726 2.3390064283 3.0111008844 H -4.1449491725 -2.8227071146 -4.4797149649 C 4.4782096351 1.4867720551 1.8578922349 H -5.7712157410 -3.4694177906 -4.1846687971 H 5.0208236256 1.1803497755 2.7567230403 C -2.9331610668 -1.8586937168 -1.9197876535 H 5.1655924011 1.4248895255 1.0104386863 H -3.2121129808 -1.3256793832 -2.8218263912 H 3.6687115812 0.7710151627 1.7003803930 C -1.9867710338 -1.2761999881 -1.0657131272 C -3.7218697820 -3.4889232294 0.8110601509 180 H -4.7410016045 -3.0940388760 0.7940849332 H -3.0207137899 -8.1329361993 -4.0874038773 H -3.0467907860 -2.6861294444 1.1136304913 H -2.2861777181 -6.7698871166 -2.1488162565 H -3.6766495492 -4.2747105858 1.5707672344 C -2.3314132951 -3.8397973901 -2.1313251375 C -1.8881605899 -4.6214489146 -0.5358672295 C -2.6538782953 -2.5572751987 -2.9100272419 H -1.1682015834 -3.8416971249 -0.2794294356 C -2.5129347777 -1.2435813290 -2.5271783021 H -1.6095005883 -5.0428932688 -1.5053427465 H -2.7828021983 -0.4889335033 -3.2551142709 H -1.8100554337 -5.4153779402 0.2126588858 N -3.1302831111 -2.9041378109 -4.1369953372 N -1.3857055309 0.1494961309 1.3981180839 Dye II-13 C -1.1862991786 0.4841954189 2.8213891733 Bis-dipole Franck-Condon point C -2.4671659454 -0.8076591376 1.7024729009 H 6.1765096223 5.6417629972 2.4354406411 C -2.4329654193 -0.3504492343 3.1738386649 C 6.0223527085 4.7077934497 2.9633603422 H -2.2839966519 -1.1383443293 3.9117338504 C 5.6580359158 2.2808998680 4.3473406960 H -3.2928002885 0.2568585105 3.4580391615 C 4.9054658295 3.9150804237 2.7564344567 H -3.3781710233 -0.6143039125 1.1300916527 C 6.9651979145 4.2603496671 3.8877396320 H -2.1667415361 -1.8494392877 1.5585144081 C 6.7907022399 3.0638012347 4.5746034646 H -1.2234436522 1.5599936857 3.0135486626 C 4.7175136570 2.7147616238 3.4326326520 H -0.2552092497 0.0781808650 3.2270815301 H 7.8497715456 4.8612931486 4.0701807773 C -3.5428948065 -1.9465954704 -5.1396283091 H 7.5384514712 2.7367016034 5.2885616548 H -2.7004816071 -1.3193512124 -5.4486639117 H 5.5246155711 1.3459254103 4.8836596749 H -4.3393422838 -1.3036691517 -4.7521504561 N 3.8108442449 4.1271773749 1.8943287667 H -3.9199810810 -2.4747587259 -6.0128371201 C 2.9107451659 3.1085086002 1.9634042008 C -0.8358327175 -3.9337676521 -1.7819555448 C 3.4129662636 2.0822927763 2.9882982618 H -0.2172680160 -3.8154338786 -2.6751990136 H 4.4752629050 5.9741309190 1.2047140530 H -0.6202157743 -4.9154008352 -1.3506821631 C 3.6604400525 5.2754862600 1.0277374133 H -0.5346647454 -3.1731183067 -1.0575697403 H 3.6796305701 4.9742829249 -0.0247769991 C -3.2131930678 -3.9819746731 -0.8780373320 H 2.7157703967 5.7886014159 1.2320510943 H -3.0398136732 -4.9581747682 -0.4164010346 C 1.7703269003 3.0933428444 1.1942102165 H -4.2733774640 -3.9141729280 -1.1350296187 H 1.6252766252 3.9247953096 0.5164774572 H -2.9938048159 -3.2133189831 -0.1333928049 C 0.7827995734 2.0777424265 1.1888858528 C 2.4542728507 1.9587828867 4.1858137900 H 0.9377403308 1.2385742938 1.8534934149 H 1.4936708217 1.5254889901 3.8971373160 C -0.2988557390 2.0374726975 0.3431085840 H 2.2646446643 2.9345675972 4.6402991062 C -1.1711108945 0.8854354614 0.3003748476 H 2.9002609272 1.3135544592 4.9479699119 C -1.7931371441 0.5264419762 -0.9550047468 C 3.6829841680 0.7119012966 2.3418837282 C -2.0288374380 -0.7880114435 -1.2758863388 H 4.3586604454 0.8083959862 1.4884449750 H -1.7620252321 -1.5418280269 -0.5470947604 H 2.7643976529 0.2319194491 1.9960149569 C -0.5052256403 3.1222707847 -0.6941442645 H 4.1556941476 0.0491573204 3.0722220151 H 0.2921535199 3.0802045885 -1.4495573826 Bis-dipole S1 minimum H -0.4162762495 4.1008669507 -0.2096835517 H 6.1661378899 5.6801872758 2.4689353625 C -2.0196044046 1.6198371402 -1.9787077314 C 6.0265241248 4.7375994479 2.9853103022 H -1.3217102200 1.4992100135 -2.8194748003 C 5.6953565425 2.2869692527 4.3448295152 H -3.0256450928 1.5115621590 -2.3993036099 C 4.9170520322 3.9276310040 2.7660526103 C -1.8591712644 3.0087984384 -1.3788788447 C 6.9713343844 4.2955889680 3.9055661113 H -1.9565315989 3.7716986569 -2.1560870317 C 6.8146887421 3.0864814808 4.5809632811 H -2.6581649985 3.1915251651 -0.6495906231 C 4.7480071495 2.7135954688 3.4350170590 H -3.9426685462 -4.5786549132 -6.3117737457 H 7.8457165571 4.9080325007 4.0992428270 C -3.5822534200 -5.0424342804 -5.4008302113 H 7.5661355545 2.7659623995 5.2942629103 C -2.6457601567 -6.2847161641 -3.0516324929 H 5.5760526342 1.3451688953 4.8723879533 C -3.1679179665 -4.3033494082 -4.3048900381 N 3.8287693194 4.1289284328 1.9136885959 C -3.5202020018 -6.4317144099 -5.2993068281 C 2.9354659833 3.0923540491 1.9811622333 C -3.0594196635 -7.0506221550 -4.1423555783 C 3.4524111338 2.0677085088 2.9909282314 C -2.7025408963 -4.9070742956 -3.1421600582 H 4.4962359337 5.9657531653 1.1970397146 H -3.8385304173 -7.0362370930 -6.1421108777 C 3.6604119082 5.2835270647 1.0585883631 181 H 3.6253524052 4.9823206192 0.0063654375 C -3.1983462167 -4.0181808284 -0.8840676007 H 2.7348829655 5.8140344215 1.3050666327 H -3.0202188785 -4.9925250489 -0.4200742756 C 1.7865232002 3.0687159742 1.2150703815 H -4.2602517096 -3.9507225664 -1.1335174212 H 1.6220985340 3.9183236616 0.5627569969 H -2.9706768969 -3.2447734446 -0.1472996110 C 0.8197618810 2.0361069019 1.1773101276 C 2.4951629151 1.9216732192 4.1896889241 H 0.9747897828 1.1744153856 1.8121639420 H 1.5334478327 1.5007714271 3.8884209977 C -0.2796581530 2.0149791110 0.3314056833 H 2.3109107398 2.8884292802 4.6650340980 C -1.1892094381 0.8995676081 0.3096400692 H 2.9386579577 1.2564348091 4.9360800328 C -1.7630127705 0.5166550235 -0.9558489393 C 3.7335760439 0.6994404562 2.3389016856 C -1.9744028350 -0.8163129582 -1.2752354379 H 4.4095258688 0.8025120599 1.4864073318 H -1.6693106723 -1.5558535713 -0.5467484403 H 2.8171707803 0.2170757923 1.9922538815 C -0.4847512644 3.1057642358 -0.6973126018 H 4.2080981061 0.0378291190 3.0693820416 H 0.3137627022 3.0647770213 -1.4521651721 Cyanine-like Franck-Condon point H -0.3932584619 4.0836425649 -0.2109114810 H 4.2935582544 6.8462183223 4.0198453120 C -2.0050807066 1.6050613179 -1.9782455380 C 4.7274082498 5.8569649855 4.1097249385 H -1.3146995530 1.4823395402 -2.8252070682 C 5.8885686757 3.3007466074 4.3570307407 H -3.0145493982 1.4951913670 -2.3916437903 C 4.1416275334 4.7350710410 3.5471646590 C -1.8398413048 2.9957379665 -1.3818262510 C 5.9199619098 5.6749317492 4.8087478338 H -1.9352113939 3.7566713988 -2.1615006112 C 6.4968492700 4.4156145784 4.9348226996 H -2.6361778984 3.1808272749 -0.6513205468 C 4.7066676414 3.4703968331 3.6609017860 H -3.9743489690 -4.5607247313 -6.3275605270 H 6.4033220913 6.5351639595 5.2596626417 C -3.6082432210 -5.0358954412 -5.4248688504 H 7.4246008202 4.2994089105 5.4842196933 C -2.6563646594 -6.3058999770 -3.0913048037 H 6.3418477436 2.3187721962 4.4564733173 C -3.1792151172 -4.3052614272 -4.3216588481 N 2.9496206384 4.6325314995 2.7984212555 C -3.5538754293 -6.4229911451 -5.3357314474 C 2.7107232265 3.3552574853 2.4063396007 C -3.0847732681 -7.0572787129 -4.1866314674 C 3.8366056160 2.4597459995 2.9402756408 C -2.7067231582 -4.9277137828 -3.1644251555 H 2.4766942464 6.6538668667 2.9385793361 H -3.8849883894 -7.0192768397 -6.1795426331 C 2.0921183690 5.7515068874 2.4684415262 H -3.0535481621 -8.1405507984 -4.1435363403 H 2.0583324786 5.9074164899 1.3854549673 H -2.2912529703 -6.8030334481 -2.1973701151 H 1.0765252948 5.5756449571 2.8345187677 C -2.3236517255 -3.8756150018 -2.1449677462 C 1.6175381353 3.0221743470 1.6329317229 C -2.6429819269 -2.5885823776 -2.9055909799 H 0.9631991602 3.8313105196 1.3330617897 C -2.4949295985 -1.2737475808 -2.5091435028 C 1.2788926750 1.7261051563 1.1908552469 H -2.7925769478 -0.5164355484 -3.2251446431 H 1.8725147882 0.8977527513 1.5557487191 N -3.1329110271 -2.9207804715 -4.1410061960 C 0.2915877030 1.4292687669 0.2746943956 N -1.3770093378 0.1227897525 1.4176353597 C 0.0492434394 0.0622335386 -0.0901029237 C -1.2761552793 0.5754027474 2.8212682070 C -0.4395947408 -0.2317277972 -1.4061837453 C -2.5731708833 -0.6999952872 1.6987573220 C -1.1457152043 -1.3875519173 -1.6593815781 C -2.4880997688 -0.3031987071 3.1849621711 H -1.3289528157 -2.0324481578 -0.8106598605 H -2.2657769150 -1.1269263412 3.8636872360 C -0.4088932688 2.5504460116 -0.4710052674 H -3.3521872828 0.2459467225 3.5594736275 H 0.3469381196 3.3004556813 -0.7311441365 H -3.4610976007 -0.3499902687 1.1628522105 H -1.1237812971 3.0592195159 0.1883289163 H -2.4342882304 -1.7651849678 1.4962810495 C -0.3652385430 0.9171118499 -2.3820462920 H -1.4207953547 1.6551816589 2.9278616688 H 0.6750005697 1.1990595529 -2.5868525307 H -0.3393139195 0.2930040488 3.3090183792 H -0.8155917712 0.6548783396 -3.3399207561 C -3.5489054434 -1.9508236513 -5.1303878950 C -1.1121707335 2.0986048360 -1.7559864683 H -2.7083969754 -1.3129962429 -5.4232867861 H -1.1723885846 2.9391008406 -2.4539727620 H -4.3514974237 -1.3192752743 -4.7359189722 H -2.1395483712 1.7841881428 -1.5444865010 H -3.9182766898 -2.4665443793 -6.0140116396 H -4.5486311052 -4.4909732514 -6.3610992038 C -0.8272560498 -3.9882179830 -1.7937160110 C -4.6256175589 -4.8336030141 -5.3356616805 H -0.2043233071 -3.8743144005 -2.6844427395 C -4.8506501255 -5.7519943521 -2.6805849256 H -0.6260652266 -4.9735734483 -1.3634369828 C -3.9260746107 -4.2378758243 -4.2991067180 H -0.5223657975 -3.2339157707 -1.0651174442 C -5.4519200860 -5.9101294640 -5.0161213904 182 C -5.5676461965 -6.3670544272 -3.7075472382 C 3.8668425640 2.4525767230 2.9518749103 C -4.0294310905 -4.6833672957 -2.9863929060 H 2.5100516580 6.6505206291 3.0092681003 H -6.0123889568 -6.3968803213 -5.8072127987 C 2.1709232028 5.7709042087 2.4664367652 H -6.2188374531 -7.2049440365 -3.4841415526 H 2.2136533095 5.9816376799 1.3924532475 H -4.9427250810 -6.1104478332 -1.6594379158 H 1.1333964862 5.5687056676 2.7475152219 C -3.1427572090 -3.8381004875 -2.0937974008 C 1.7010097469 3.0474429809 1.5691352482 C -2.5531648340 -2.8443003795 -3.1037199250 H 1.0881874584 3.8775870143 1.2366861787 C -1.6994017466 -1.7818075617 -2.8972954166 C 1.3357325654 1.7673657729 1.1119138349 H -1.4423131126 -1.1901502979 -3.7663342610 H 1.8799121222 0.9097515777 1.4851607501 N -3.0341381390 -3.1459976698 -4.3385454397 C 0.3513929862 1.5164435517 0.1558531272 N 0.3097371830 -0.9227460345 0.8021386041 C 0.0118947858 0.1750296261 -0.1926424590 C 0.1791893763 -1.0014655507 2.2709121661 C -0.6171584447 -0.1111656686 -1.4515903022 C 0.7896849533 -2.3128692354 0.6753698622 C -1.2715414786 -1.3165630001 -1.6616270841 C 0.7350703217 -2.4407291696 2.2128284934 H -1.3607368558 -1.9614768966 -0.7971718911 H 1.7084904857 -2.5638952497 2.6877601872 C -0.2867840428 2.6755825994 -0.5806873215 H 0.0573830275 -3.2094158073 2.5839515220 H 0.5176611208 3.3018054033 -0.9883139250 H 0.1340965167 -2.9990044194 0.1396544816 H -0.8340646308 3.3151763306 0.1240154789 H 1.7861737625 -2.3635316101 0.2252087644 C -0.6460712821 1.0243173667 -2.4402181460 H -0.8665009997 -0.9197755692 2.5855197082 H 0.3617286171 1.2469554006 -2.8152035015 H 0.7700482756 -0.2897886792 2.8462300741 H -1.2643800680 0.7846451010 -3.3066787258 C -2.6900742759 -2.4138263335 -5.5387804222 C -1.2111666151 2.2532848541 -1.7221023414 H -1.6111446414 -2.4519108823 -5.7167251479 H -1.3363665057 3.0863073201 -2.4203857363 H -2.9997444627 -1.3673576048 -5.4557201917 H -2.2065901884 2.0052802318 -1.3377831765 H -3.1980388584 -2.8573429967 -6.3922520956 H -4.5977281326 -4.6594736653 -6.2721762877 C -2.0513697691 -4.7199894767 -1.4604519603 C -4.6366045746 -4.9928749147 -5.2415781397 H -1.4449535989 -5.2085716265 -2.2272884956 C -4.7746025209 -5.8759994228 -2.5630879763 H -2.5170830483 -5.4991004088 -0.8503104308 C -3.9445114991 -4.3441130080 -4.2230053163 H -1.3867991897 -4.1418933762 -0.8150631179 C -5.4018083046 -6.0996067525 -4.8910143536 C -3.9826243984 -3.1287098855 -1.0178652751 C -5.4743734263 -6.5417401560 -3.5706009573 H -4.4875982634 -3.8736876014 -0.3965042446 C -4.0109257100 -4.7743694414 -2.8952819897 H -4.7482439063 -2.4947143358 -1.4723220931 H -5.9537441358 -6.6252986302 -5.6631305179 H -3.3668200137 -2.5049639984 -0.3656467676 H -6.0800347373 -7.4072838886 -3.3251496894 C 3.3183556615 1.4098922926 3.9397984112 H -4.8355595894 -6.2226702750 -1.5357352914 H 2.7183435247 0.6393109909 3.4498135586 C -3.1596918747 -3.8714893581 -2.0280974422 H 2.7134428284 1.8735468786 4.7232157305 C -2.6371795478 -2.8705230680 -3.0589289240 H 4.1667944928 0.9135820095 4.4189048637 C -1.8480828550 -1.7503425817 -2.8772271521 C 4.6217910713 1.7965035874 1.7948554972 H -1.6545538126 -1.1480174795 -3.7570126089 H 4.9851224093 2.5423276106 1.0835117473 N -3.1130902963 -3.2262916469 -4.2939665955 H 4.0097764286 1.0746887499 1.2488569788 N 0.3013294619 -0.8532044855 0.6736717343 H 5.4881610935 1.2683326012 2.2029156808 C 0.1383431060 -1.0073013814 2.1243519975 Cyanine-like S1 minimum C 0.9600358436 -2.1532077254 0.4945038295 H 4.3429114639 6.8394811607 4.0577100929 C 0.7741274966 -2.4122487501 2.0073879997 C 4.7621348699 5.8449623382 4.1569352952 H 1.7005161278 -2.5476440619 2.5661121116 C 5.8898318570 3.2705183953 4.4207065624 H 0.0954222684 -3.2322166431 2.2442651977 C 4.1739526687 4.7276662303 3.5728768178 H 0.4569926735 -2.8564432277 -0.1753398304 C 5.9317580934 5.6465176901 4.8828310935 H 2.0024631221 -2.0587963593 0.1664156208 C 6.4936826824 4.3779169799 5.0180851947 H -0.9118382660 -0.9897546161 2.4383985365 C 4.7274122894 3.4516840583 3.6967249780 H 0.6904243127 -0.2956364765 2.7450840564 H 6.4142299755 6.4989300627 5.3495627647 C -2.8062951756 -2.5154760757 -5.5165671294 H 7.4061025723 4.2512840820 5.5906346464 H -1.7242328904 -2.3957456021 -5.6208850150 H 6.3329793764 2.2846954056 4.5262706530 H -3.2758644543 -1.5255730009 -5.5257760074 N 3.0107632986 4.6413732546 2.8041096743 H -3.1720943152 -3.0852314414 -6.3682707289 C 2.7707740383 3.3596750257 2.3926606426 C -2.0201774072 -4.6841493125 -1.3811802105 183 H -1.3909611349 -5.1555401418 -2.1403893598 H 4.3637997674 -7.0105924973 -0.8615873391 H -2.4445510853 -5.4736713098 -0.7541458259 C 4.4813908585 -6.3953269660 0.0231765766 H -1.3872806177 -4.0591909623 -0.7475515903 C 4.8176755520 -4.8160890768 2.3302406177 C -4.0213605393 -3.1849911445 -0.9501626177 C 3.6096313845 -5.3618799535 0.3261112871 H -4.4545494334 -3.9418094481 -0.2897265863 C 5.5368639699 -6.6279369225 0.9044543132 H -4.8406358956 -2.6208963400 -1.4028725826 C 5.7089585867 -5.8519609056 2.0451407832 H -3.4292423492 -2.4997145605 -0.3398583418 C 3.7682611366 -4.5769091934 1.4638697668 C 3.3145858844 1.3978524678 3.9317233332 H 6.2338685867 -7.4314827464 0.6904945142 H 2.7086802020 0.6458186079 3.4209138761 H 6.5376853664 -6.0520919327 2.7154283270 H 2.7054210217 1.8617733575 4.7116590017 H 4.9530429819 -4.2104719489 3.2219621449 H 4.1481696146 0.8811861981 4.4160372924 C 2.6623178888 -3.5396674291 1.5226246765 C 4.6740832097 1.7800073308 1.8238572122 C 1.8721441327 -3.8622718383 0.2443783523 H 5.0757165123 2.5241122067 1.1315132825 C 0.7566210504 -3.2619515734 -0.2700917476 H 4.0596221077 1.0787583009 1.2548013499 H 0.3771803165 -3.6554006835 -1.2042869445 H 5.5146219425 1.2269197538 2.2530259592 N 2.4780475459 -4.9193808694 -0.3811327649 N -2.0952169848 -0.3982947956 1.6735809294 Dye II-14 C -2.8084900916 0.7196706213 2.3327525195 Bis-dipole Franck-Condon point H -2.8195494937 1.5623986803 1.6506131097 H 0.6349376915 8.2892412142 -1.0881209221 C -2.1393344665 -1.6654905315 2.4479377984 C 0.8789553559 7.8614932833 -0.1224432698 H -2.3772991084 -1.3836711219 3.4741903318 C 1.5287573768 6.7839474921 2.3979682200 H -1.1511303669 -2.1121117927 2.4764844009 C 0.5510003985 6.5586853649 0.2154564513 H -2.2304577123 1.0111454721 3.2165813052 C 1.5465749165 8.6254137538 0.8342830234 C 2.0016619642 -5.4959332094 -1.6164207180 C 1.8704565662 8.0993219342 2.0799823804 H 2.0109557871 -4.7539314971 -2.4219767373 C 0.8669294961 6.0181532314 1.4572328156 H 0.9814159943 -5.8763329612 -1.4992568773 H 1.8159019870 9.6491800057 0.5965310134 H 2.6467100991 -6.3238115798 -1.9034381402 H 2.3901457468 8.7133067675 2.8073439819 C -0.6708366488 4.4477764220 2.6469811604 H 1.7825135858 6.3747950606 3.3717179713 H -1.0486424453 3.4258873166 2.7358920968 N -0.1134695840 5.5817836974 -0.5510622012 H -1.5201652220 5.1133297511 2.4731994580 C -0.2493271751 4.4097348641 0.1341235636 H -0.2194483600 4.7206804032 3.6050147149 C 0.3758491373 4.5846308689 1.5263748223 C 1.5601774608 3.6277657025 1.7458009362 H -0.3589664778 6.7942519011 -2.2213757415 H 2.2945001886 3.7240077593 0.9421003291 C -0.5907099929 5.7807799542 -1.9010985550 H 1.2407305972 2.5836100529 1.7914934076 H -0.1079329920 5.0799359098 -2.5899626290 H 2.0588278146 3.8696594277 2.6887935419 H -1.6749017797 5.6388577967 -1.9531656509 C 3.2589573346 -2.1224740615 1.4811710971 C -0.8577940448 3.3117128975 -0.4193658530 H 3.8619627343 -1.9786991268 0.5810735332 H -1.2275147063 3.4137224977 -1.4312158533 H 3.9065942175 -1.9692815911 2.3494455307 C -1.0524915729 2.0590881191 0.2265268587 H 2.4840178965 -1.3517894393 1.4978332879 H -0.7272413969 1.9993495665 1.2591693647 C 1.8197430354 -3.7515538759 2.7928258045 C -1.5524330606 0.9128520615 -0.3286030884 H 2.4592144324 -3.6652400839 3.6760329226 C -1.5813106525 -0.3218787389 0.4504898406 H 1.3660311510 -4.7458798063 2.8025889318 C -1.0075833460 -1.4986310846 -0.2256223632 H 1.0224021191 -3.0095322751 2.8891041333 C 0.0428195271 -2.1711159728 0.3163040976 C -3.1577234746 -2.6685450197 1.9201573993 H 0.4073976422 -1.8265213465 1.2773865471 C -4.2458754689 0.3878184301 2.7192365455 C -1.9136045988 0.7828042446 -1.7960302057 H -3.1551040483 -3.5522008888 2.5644877394 H -1.6324393393 1.6899779819 -2.3325559456 H -2.9051128571 -2.9900564365 0.9082426044 H -3.0047391962 0.6949306987 -1.8936432327 H -4.8357703452 0.1128254601 1.8409454159 C -1.5047847372 -1.6923997234 -1.6418172306 H -4.6950115522 1.2838702079 3.1558907584 H -1.0080099747 -2.5450278868 -2.1057175498 H -4.3262756153 -0.4101168853 3.4599670533 H -2.5793872102 -1.9217701077 -1.6404119448 H -4.1680984670 -2.2558836118 1.9146169260 C -1.2576492517 -0.4266189370 -2.4628908774 Bis-dipole S1 minimum H -0.1782408261 -0.2594780252 -2.5457883288 H 0.2860838718 8.4573592234 -1.3483677394 H -1.6494567350 -0.5469899241 -3.4779953228 C 0.3785756838 8.1904280933 -0.3017331995 184 C 0.6236791619 7.5335170424 2.4248502099 H -0.6149162792 -1.4648278603 2.9945802167 C 0.2025782892 6.8901608443 0.1469112506 H -3.3209839846 0.7118080464 3.1077515769 C 0.6821992334 9.1663018634 0.6468943473 C 1.1400623534 -6.1261535344 -1.1980250776 C 0.8045424105 8.8497434605 1.9950838515 H 1.1823324434 -5.6393140316 -2.1764242627 C 0.3218118203 6.5578742818 1.4947111357 H 0.1136481741 -6.1138667502 -0.8276811826 H 0.8263454524 10.1910805163 0.3209411342 H 1.4522487860 -7.1627342527 -1.3026095550 H 1.0408143417 9.6264998334 2.7139556758 C -1.1334018173 4.8380916828 2.5944989824 H 0.7217996318 7.2861742446 3.4780178697 H -1.3373107481 3.7741324434 2.7355970561 N -0.1038267286 5.7335369017 -0.5840764312 H -2.0315505769 5.3077952192 2.1853684922 C -0.1997610055 4.6308700213 0.2323539366 H -0.9410431221 5.2769902778 3.5780516075 C 0.0783306803 5.0709913381 1.6747492280 C 1.3378640970 4.3909583631 2.2411517935 H -0.1147072094 6.6741347171 -2.4366250402 H 2.2016430810 4.5705982532 1.5957386420 C -0.2834728156 5.6855187205 -2.0140004614 H 1.2046242082 3.3110762263 2.3382240547 H 0.4288197219 4.9890157734 -2.4702985543 H 1.5662712709 4.7973672042 3.2311002564 H -1.2992864971 5.3653181776 -2.2715399760 C 3.6326592910 -2.6263714953 0.8957105604 C -0.4861875731 3.3812438366 -0.2554598732 H 3.9754583378 -2.6614538258 -0.1414804837 H -0.6439480729 3.3040024249 -1.3258409024 H 4.5085548070 -2.4965416201 1.5365064666 C -0.5851264947 2.1822974927 0.4933801176 H 2.9954539343 -1.7484350374 1.0168024821 H -0.4817188418 2.2357755348 1.5709452146 C 2.4132347255 -3.8719081228 2.7498028862 C -0.7832076128 0.9129024200 -0.0320141178 H 3.2709384332 -3.7518671522 3.4165888426 C -1.0765740890 -0.1949114568 0.7894255738 H 1.8949449626 -4.7927770119 3.0291275271 C -0.8072800179 -1.5227141501 0.1821379081 H 1.7373446011 -3.0306832493 2.9177151749 C 0.2942489546 -2.2721587570 0.5485682227 C -2.6237230660 -2.2591586516 3.0070685887 H 0.9210006823 -1.8559677336 1.3275372196 C -4.1027745546 0.4505229346 1.1140153637 C -0.8600462785 0.7094379199 -1.5445043186 H -2.4163776007 -2.9520509843 3.8288545088 H -0.0327850502 1.2248185814 -2.0435552959 H -2.5502922542 -2.8125155791 2.0658574350 H -1.7717730152 1.2177794234 -1.8878320238 H -3.7817544963 0.5746238869 0.0757171106 C -1.5903842024 -1.7374456270 -1.0651824660 H -4.9449238421 1.1285482814 1.2829836538 H -1.5570492662 -2.7509289779 -1.4746902665 H -4.4600762977 -0.5748984183 1.2452414575 H -2.6380650131 -1.4597544478 -0.9160923489 H -3.6556909293 -1.9140436613 3.1161878478 C -0.9033895355 -0.7454841950 -2.0479720826 Cyanine-like Franck-Condon point H 0.1155927349 -1.1084248466 -2.2195743712 H -2.3741513178 7.3412183402 -4.8119609291 H -1.4171902299 -0.7872758483 -3.0132311173 C -2.0416422170 7.4397967681 -3.7850189082 H 3.4524088129 -7.8244417990 -0.9805234658 C -1.1749442069 7.7337156438 -1.1195130824 C 3.8853060320 -7.1559397293 -0.2455368583 C -1.6814306125 6.3473044259 -3.0133771531 C 5.0533562070 -5.4133635058 1.6471117825 C -1.9596258981 8.6988231457 -3.1917891425 C 3.2597964911 -5.9873591852 0.1625602966 C -1.5320663865 8.8499068945 -1.8769555090 C 5.1234028189 -7.4415142207 0.3212816804 C -1.2519730311 6.4810373400 -1.6980951713 C 5.7016301135 -6.5848362373 1.2563983436 H -2.2340124652 9.5736181093 -3.7717918512 C 3.8243656489 -5.1163119763 1.0879933963 H -1.4757008727 9.8401092576 -1.4383036374 H 5.6457763505 -8.3443353158 0.0249552925 H -0.8414520605 7.8544445378 -0.0929641817 H 6.6684774985 -6.8303287340 1.6812116687 N -1.6690611268 4.9793715762 -3.3574802034 H 5.5143132198 -4.7497358266 2.3716432812 C -1.2335445707 4.2061530755 -2.3287026367 C 2.9079404107 -3.9285653971 1.2902491150 C -0.9406663539 5.1123214899 -1.1255789334 C 1.7684552247 -4.2683607800 0.3292017881 H -1.1953316249 3.9992034986 -5.1565298976 C 0.6341004096 -3.5231506204 0.0097555980 C -2.0514758884 4.4596861901 -4.6533843754 H -0.0296406869 -3.9390422756 -0.7381678966 H -2.8449811725 3.7142648795 -4.5471768745 N 2.0178766160 -5.4593710558 -0.2502350815 H -2.4237540414 5.2723382949 -5.2733483898 N -1.8035776423 -0.1096753613 1.9709082746 C -1.0938743823 2.8398682499 -2.4529885010 C -2.9657702903 0.7813086248 2.0763208708 H -1.3332456404 2.4113859622 -3.4178229712 H -2.6626826914 1.8195592869 1.9212321622 C -0.6600457063 1.9598003393 -1.4390921958 C -1.6409441472 -1.0905791028 3.0352995503 H -0.5015132923 2.3802322423 -0.4536506316 H -1.7335979790 -0.5648650214 3.9931751250 C -0.3770913799 0.6166135509 -1.5755576017 185 C 0.0753892204 -0.1462578026 -0.4485732035 H 0.6071733074 -3.9337381833 4.3830809285 C 0.8125997341 -1.3516255105 -0.6719051374 H 0.8630507264 -2.7055361834 3.1374183992 C 0.8268844843 -2.3386164366 0.2979845137 C 0.5335280672 5.0350683387 -0.6932832991 H 0.2399148118 -2.1568000239 1.1893707343 H 1.2000300784 5.2451951742 -1.5335255780 C -0.2902779267 -0.0735097298 -2.9141727975 H 0.7903540597 4.0514497818 -0.2929289442 H -0.5514716112 0.6030629322 -3.7286262146 H 0.7273667448 5.7781207969 0.0854527736 H -0.9879065579 -0.9190821837 -2.9678114487 C -1.8881923943 4.8159457458 0.0512003204 C 1.4536846660 -1.6285477314 -2.0200581248 H -1.7020146242 3.8333306910 0.4907319565 H 2.5400062202 -1.7370389245 -1.9064724151 H -2.9332663476 4.8563012280 -0.2664935789 H 1.0898086420 -2.6026344607 -2.3704961828 H -1.7449526131 5.5669517510 0.8331980492 C 1.1438517411 -0.5782454849 -3.0858181090 Cyanine-like S1 minimum H 1.8259907561 0.2741243977 -2.9969733179 H -2.4484752646 7.4003298605 -4.7331659734 H 1.2956638311 -1.0076172985 -4.0806821032 C -2.1293321189 7.4961712208 -3.7018912937 H 3.0845058427 -8.4281320943 1.3319510706 C -1.2889619137 7.7796976982 -1.0213244276 C 2.3990888396 -7.9896803260 2.0480891289 C -1.7365951501 6.3995248964 -2.9406497613 C 0.6204121573 -6.8782889783 3.9318550727 C -2.0931003598 8.7447460964 -3.0914193347 C 1.8844844472 -6.7127415001 1.8977703260 C -1.6788564273 8.8924441142 -1.7682624496 C 2.0021307136 -8.7113355241 3.1727626694 C -1.3176902700 6.5325973161 -1.6143366888 C 1.1240690992 -8.1679700780 4.1049002583 H -2.3913689260 9.6191350056 -3.6601248982 C 1.0073290794 -6.1541445680 2.8199848081 H -1.6583428622 9.8789565693 -1.3180795934 H 2.3878805701 -9.7147312276 3.3184980069 H -0.9666183841 7.8999447906 0.0087199016 H 0.8299604131 -8.7500898007 4.9713478132 N -1.6769962572 5.0527846975 -3.2999487650 H -0.0648914831 -6.4572951118 4.6617705237 C -1.2102346672 4.2763061515 -2.2730033953 C 0.6358991343 -4.7524707727 2.3788748982 C -0.9604231850 5.1700835217 -1.0585373223 C 1.4292129195 -4.6249084337 1.0732594884 H -1.1617916145 4.1647500364 -5.1365313202 C 1.4975934691 -3.5699543543 0.1828022024 C -2.0421787265 4.5387237832 -4.6025042114 H 2.1250634774 -3.7090486227 -0.6882119366 H -2.7670222745 3.7257802009 -4.4996404304 N 2.1134268733 -5.7764467592 0.8661335883 H -2.4975058770 5.3322732324 -5.1911827931 N -0.2113399781 0.2668292723 0.8328254653 C -1.0072535055 2.9170841909 -2.4224931242 C 0.7922926290 0.2317575172 1.9047404390 H -1.2146702351 2.5026209697 -3.4019451466 H 1.7178597836 -0.1484334402 1.4741769918 C -0.5608567067 2.0228464188 -1.4243343511 H 0.4935288408 -0.4677011859 2.6933311880 H -0.4407918250 2.4018758845 -0.4165256751 C -1.5451908507 0.7562299079 1.2067892088 C -0.2380655341 0.6849310697 -1.6106512190 H -2.1710105679 0.7128664723 0.3164594336 C 0.1128071452 -0.1479206706 -0.4922488272 H -1.5017004093 1.8059414649 1.5179077940 C 0.7553686906 -1.4009098379 -0.7036162291 C 1.0428084997 1.6076682352 2.5156873536 C 0.7728384623 -2.3704701673 0.3051775545 H 1.3285100847 2.3329244994 1.7475662607 H 0.2192902862 -2.1435900079 1.2074716713 H 1.8617511101 1.5403739204 3.2375236241 C -0.1221792797 0.0577318874 -2.9744774493 H 0.1703085085 1.9939743470 3.0494245636 H -0.2332120029 0.8014480177 -3.7652195462 C -2.1829049817 -0.0738438017 2.3179539513 H -0.9101935693 -0.6924126571 -3.1268347566 H -1.6510962974 0.0197219872 3.2685950591 C 1.3685393215 -1.7301035787 -2.0487015363 H -2.2209954404 -1.1327634611 2.0441206309 H 2.4232735757 -2.0052867225 -1.9220713816 H -3.2082239789 0.2689347590 2.4833265570 H 0.8711853677 -2.6288581683 -2.4381423128 C 2.9727943826 -6.0118809786 -0.2761575147 C 1.2483509656 -0.6115978766 -3.0795657388 H 3.8018357153 -5.2980687745 -0.2876459092 H 2.0222239776 0.1463006173 -2.9143688961 H 2.4069462126 -5.9160573850 -1.2075484152 H 1.4066576990 -1.0166422025 -4.0835206393 H 3.3802667518 -7.0187797127 -0.2209019785 H 3.0422589304 -8.4580622038 1.3978786751 C -0.8799787884 -4.6497806488 2.1344742848 C 2.3847971866 -8.0006919811 2.1282345327 H -1.4160568992 -4.8678738836 3.0624935416 C 0.6663059958 -6.8412394864 4.0450103576 H -1.2065527532 -5.3698443386 1.3798913762 C 1.8731554685 -6.7174043250 1.9681379512 H -1.1717354387 -3.6506107359 1.8019804868 C 2.0175603427 -8.6967136243 3.2748334657 C 1.1035262085 -3.7299207154 3.4301701312 C 1.1698473687 -8.1302931860 4.2256014074 H 2.1825653360 -3.7959448649 3.5914921148 C 1.0207763306 -6.1376847259 2.9101664447 186 H 2.3997295185 -9.7004593130 3.4278036308 H 1.0256538771 10.0475232758 0.5989792850 H 0.9004388445 -8.6964532392 5.1106583880 H 1.8217472689 9.1135705973 2.7409036312 H 0.0054636003 -6.4049596802 4.7882625473 H 1.5198840178 6.7014463230 3.2420653256 C 0.6389789552 -4.7448187506 2.4546515481 N -0.4809563032 5.8219020719 -0.6085960561 C 1.3878369432 -4.6472829259 1.1274210419 C -0.4390952078 4.6175537813 0.0349517111 C 1.4174136680 -3.6147161844 0.2017141768 C 0.2347372230 4.8212467379 1.4002714828 H 1.9977505854 -3.7931504137 -0.6957367416 H -0.9766252048 7.0555999917 -2.2071297147 N 2.0783294885 -5.8085906971 0.9263165300 C -1.0513425080 6.0079101161 -1.9234548329 N -0.1955658834 0.2791492509 0.7980014734 H -0.5173762765 5.4075348515 -2.6675647527 C 0.8084714758 0.3236229487 1.8587661223 H -2.1079644053 5.7217327238 -1.9305069806 H 1.6597558336 -0.2902798822 1.5604349751 C -0.9307764317 3.4730203131 -0.5376141713 H 0.3995473684 -0.1269679576 2.7722595759 H -1.3542978980 3.5687082617 -1.5285252467 C -1.5691280815 0.6063890934 1.1767470621 C -0.9382237968 2.1782516964 0.0566426106 H -2.1076920855 0.9398696465 0.2876898841 H -0.5826885111 2.1248177836 1.0768748289 H -1.5546360587 1.4533805147 1.8727452134 C -1.2848470556 1.0001348440 -0.5450775956 C 1.2885030360 1.7436959042 2.1528290255 C -1.1767954100 -0.2791695116 0.1558689888 H 1.7655385972 2.1769823221 1.2684787681 C -0.5752033325 -1.3922813490 -0.5641059433 H 2.0208439361 1.7385667377 2.9662791489 C 0.2781078020 -2.2430255499 0.0927334597 H 0.4646135602 2.3982683032 2.4538663051 H 0.4600725466 -2.0375307980 1.1406440131 C -2.3119537915 -0.5700126205 1.8072440529 C -1.6239987459 0.9007375204 -2.0178237262 H -1.8073119895 -0.9308646908 2.7094694601 H -1.5413898044 1.8785842222 -2.4923980300 H -2.3888712306 -1.4011989086 1.0994991676 H -2.6684455087 0.5836719593 -2.1424203137 H -3.3261017296 -0.2730235837 2.0923465066 C -0.8000040966 -1.4634182552 -2.0603682554 C 2.9166347541 -6.0631966800 -0.2263761090 H -0.0706691776 -2.1340310946 -2.5168973263 H 3.6844026197 -5.2890203866 -0.3163043020 H -1.7889449691 -1.8975328330 -2.2633651418 H 2.3202913282 -6.0810429472 -1.1444053478 C -0.7103314979 -0.0940909985 -2.7268649122 H 3.4084238497 -7.0264626275 -0.1115814835 H 0.3226488323 0.2688879153 -2.6845584377 C -0.8861176191 -4.6376401720 2.2590998652 H -0.9845642650 -0.1744060641 -3.7834520382 H -1.3920444686 -4.8339230323 3.2089001644 H 4.3944203142 -7.3039890220 -0.8184518946 H -1.2414566471 -5.3692187698 1.5289975457 C 4.3764661314 -6.7980145992 0.1400092908 H -1.1793133895 -3.6421960035 1.9182207758 C 4.3562531388 -5.5076892436 2.6445464235 C 1.1369138831 -3.6976839414 3.4711022634 C 3.5327604301 -5.7304099647 0.3990643861 H 2.2175111234 -3.7729857680 3.6165959511 C 5.2214122340 -7.2136135309 1.1685188392 H 0.6526324390 -3.8678549595 4.4369966711 C 5.2161857428 -6.5807555422 2.4067523350 H 0.9037894241 -2.6799792343 3.1499670180 C 3.5151019808 -5.0874580308 1.6318894318 C 0.5139475252 5.1372325827 -0.6126105718 H 5.8933372678 -8.0472676841 0.9935938065 H 1.1799928148 5.3923565307 -1.4405808353 H 5.8832020683 -6.9221958909 3.1907352721 H 0.7994330770 4.1532794092 -0.2344249376 H 4.3538455724 -5.0145955742 3.6124249217 H 0.6724896533 5.8664111777 0.1871260485 C 2.4910784698 -3.9695945662 1.6052801717 C -1.8991515368 4.8194804617 0.1143015804 C 1.9518152369 -4.0834593804 0.1718733662 H -1.6855533728 3.8302998566 0.5261890056 C 0.9982981390 -3.3298726023 -0.4695217076 H -2.9457034647 4.8422132106 -0.2000229282 H 0.7760891165 -3.5971074081 -1.4941609526 H -1.7715927379 5.5535736252 0.9151483346 N 2.5920273290 -5.1136678781 -0.4495969767 N -1.6269233341 -0.4341780493 1.4062545248 Dye II-15 C -2.2937722337 0.6274899252 2.1963852653 Bis-dipole Franck-Condon point H -2.8948579530 1.2399472146 1.5204223390 H -0.0788502215 8.6143485034 -1.0769606899 C -1.8879861814 -1.7396450634 2.0507193367 C 0.2641587630 8.1868941755 -0.1417019097 H -1.1117109271 -1.9548326109 2.7937865041 C 1.1685372162 7.1107609009 2.2991468835 H -1.8786356045 -2.5299820944 1.3032723670 C 0.1069894603 6.8438753881 0.1602564042 H -1.5535222849 1.2769899907 2.6666121771 C 0.8893403968 8.9920092272 0.8099558164 C 2.3374542048 -5.5095833754 -1.8170481004 C 1.3380726772 8.4671001532 2.0168638923 H 2.5411533978 -4.6811011251 -2.5029864603 C 0.5510807867 6.3040131680 1.3626629008 H 1.2970474310 -5.8259977684 -1.9420657712 187 H 2.9860084737 -6.3424162606 -2.0801424426 C -0.5737746348 -1.3223411481 -2.0597610682 C -0.7282770000 4.5254290430 2.5635101758 H 0.2920812654 -1.8259824813 -2.4966107806 H -0.9856172891 3.4652128528 2.6226965642 H -1.4524283401 -1.9299318766 -2.3200066892 H -1.6546855988 5.0963284804 2.4616661389 C -0.7193368013 0.0529825595 -2.7141865130 H -0.2595549361 4.8094243883 3.5100360540 H 0.2473562604 0.5689897485 -2.7028938534 C 1.5313927381 4.0031970224 1.5260159605 H -1.0123148848 -0.0624980703 -3.7626103553 H 2.2123477456 4.2207153662 0.6993318450 H 4.3205625126 -7.3647480864 -0.8171040539 H 1.3388308357 2.9274739899 1.5333420433 C 4.3225506870 -6.8636253193 0.1441242981 H 2.0408062084 4.2614482074 2.4589431917 C 4.3597486959 -5.5798421751 2.6538010942 C 3.1758660773 -2.6145679329 1.8540319320 C 3.5034721986 -5.7750332726 0.4148335203 H 3.9556709316 -2.4277237108 1.1113631399 C 5.1673513855 -7.3017374345 1.1610260328 H 3.6455482111 -2.6161357192 2.8419388042 C 5.1914655947 -6.6725773326 2.4026201954 H 2.4667087180 -1.7839274134 1.8194074118 C 3.5170532342 -5.1348560966 1.6538525416 C 1.3929831319 -4.2415131016 2.6492507171 H 5.8178430488 -8.1505177308 0.9766740756 H 1.8382077645 -4.2901043571 3.6469851339 H 5.8603481818 -7.0318243862 3.1771633161 H 0.8941311116 -5.1946064428 2.4559591379 H 4.3812533442 -5.0899955875 3.6231396916 H 0.6365032288 -3.4538379430 2.6570687723 C 2.5233378649 -3.9907069450 1.6427668526 C -3.2366787213 -1.5340600593 2.7252180591 C 1.9718081833 -4.0808445312 0.2172521785 C -3.1299137247 -0.1059334919 3.2543745843 C 1.0528959757 -3.2749389484 -0.4192809235 H -3.4218177379 -2.2712320841 3.5089430979 H 0.8260638391 -3.5207810880 -1.4500208350 H -4.0372237626 -1.6171846242 1.9835435677 N 2.5731369276 -5.1377650515 -0.4154634841 H -4.1002693498 0.3717983362 3.4006447143 N -1.7281023511 -0.4474426614 1.3942099958 H -2.6105869825 -0.0979207203 4.2171673422 C -2.5802570982 0.5712328772 2.0314409837 Bis-dipole S1 minimum H -3.3190389839 0.9422377542 1.3106951780 H -0.1939757702 8.6536866392 -1.0157902563 C -2.0106699461 -1.7777959792 1.9615718983 C 0.1956146783 8.2244210241 -0.1000405494 H -1.2236156929 -2.0742088565 2.6651562497 C 1.2241767923 7.1390600281 2.2938122459 H -2.0433462330 -2.5232375503 1.1650672073 C 0.0905421767 6.8693244724 0.1906468647 H -1.9953043156 1.4283633147 2.3720322339 C 0.8286928206 9.0327883490 0.8389577016 C 2.2837054687 -5.5299199059 -1.7758825852 C 1.3367917276 8.5034676215 2.0237745945 H 2.5346630687 -4.7245264589 -2.4745672656 C 0.5993607007 6.3245622540 1.3694881030 H 1.2226469126 -5.7759653584 -1.8875938067 H 0.9263736911 10.0948775614 0.6408070219 H 2.8721802489 -6.4077515790 -2.0343667596 H 1.8233294661 9.1566105098 2.7399137389 C -0.5139665965 4.4492992369 2.6059983471 H 1.6236251210 6.7300859781 3.2171488560 H -0.7101579731 3.3755202339 2.6433901676 N -0.4963077111 5.8451856252 -0.5625224169 H -1.4717629511 4.9756439243 2.5940337931 C -0.3969001073 4.6354994200 0.0655133125 H 0.0115521813 4.7242623203 3.5248583439 C 0.3468709294 4.8315645666 1.3882931411 C 1.6890094638 4.0719055563 1.3996914549 H -1.0605533546 7.0853807001 -2.1357309784 H 2.3007191035 4.3449535800 0.5362205514 C -1.1218891407 6.0367289977 -1.8541948962 H 1.5441189069 2.9892846742 1.3896040832 H -0.6134146245 5.4403375198 -2.6180109768 H 2.2464066004 4.3313322086 2.3041247117 H -2.1763525477 5.7457835341 -1.8185577385 C 3.2449379965 -2.6541175680 1.8959460022 C -0.8984081644 3.4817389761 -0.5008756986 H 4.0283604391 -2.4858776141 1.1525746812 H -1.3988015985 3.5884497015 -1.4556114125 H 3.7147875519 -2.6713208671 2.8838127114 C -0.8206182701 2.1716675077 0.0422626149 H 2.5551625758 -1.8077133151 1.8629953933 H -0.3545602069 2.0580496152 1.0139343169 C 1.4249659711 -4.2321763810 2.6958696264 C -1.3048120479 1.0255370580 -0.5433766101 H 1.8731291218 -4.2750963054 3.6928397228 C -1.2113102803 -0.2787364121 0.1401266357 H 0.9103967882 -5.1792891517 2.5151472360 C -0.4448678082 -1.2770408709 -0.5457182243 H 0.6825739369 -3.4311834570 2.6931283111 C 0.3811590008 -2.1586286354 0.1370155352 C -3.3389622378 -1.6004239274 2.6911573500 H 0.5225522541 -1.9633933124 1.1932596433 C -3.2534009115 -0.1610017896 3.1919956094 C -1.7463507156 0.9252511066 -1.9744260769 H -3.4734756126 -2.3310567709 3.4918045862 H -1.8210807046 1.9015876937 -2.4575319817 H -4.1721381841 -1.7108588380 1.9892514547 H -2.7348785127 0.4519057445 -2.0326132856 H -4.2240731213 0.2737157445 3.4392222825 188 H -2.6269665268 -0.1083348086 4.0883417298 C -0.1972780781 1.2004597392 -1.2525756911 Cyanine-like Franck-Condon point H -1.0996154180 1.7835980372 -1.0689923211 H 8.8108258670 -0.5040163616 2.8121686602 C 0.4521745979 -1.0907467634 -0.7500848092 C 8.5154400847 -0.2616323177 1.7978357994 H -0.3832855562 -1.7942224016 -0.6269585790 C 7.7838552654 0.3709967033 -0.8503648442 H 1.3180713452 -1.5278919779 -0.2526669309 C 7.1896795799 -0.1199099218 1.4232201651 H 0.6404869898 1.9098627279 -1.3150958870 C 9.4823782828 -0.0785518090 0.8104247837 C -5.9512051919 2.8889115178 2.4615865944 C 9.1268062121 0.2337646443 -0.4976134201 H -6.9582978877 3.2856876671 2.5692147027 C 6.8170221233 0.1925706939 0.1211518169 H -5.2625751340 3.7268500038 2.3207021501 H 10.5298889565 -0.1825548077 1.0725995495 H -5.6837992298 2.3579484089 3.3805848413 H 9.8979865086 0.3717614945 -1.2474952914 C 4.7810055134 -0.8040611060 -0.9356986563 H 7.5100674908 0.6146971238 -1.8727347522 H 3.6907951226 -0.7962851743 -1.0023795917 N 6.0228379914 -0.2477667979 2.2088207806 H 5.0979740747 -1.8026857547 -0.6243844834 C 4.9021163174 -0.0270127765 1.4813177913 H 5.1818117597 -0.6204239198 -1.9365759266 C 5.3063476698 0.2717613986 0.0325712315 C 4.8677248937 1.6811374431 -0.4022018059 H 5.5683148485 0.2523554090 4.1976722265 H 5.2336723460 2.4392074536 0.2949096506 C 6.0194916388 -0.5623244830 3.6232682754 H 3.7807023279 1.7694154059 -0.4625299011 H 5.4589511936 -1.4829649252 3.8093345489 H 5.2806367664 1.9051292798 -1.3899095767 H 7.0422978232 -0.7034666513 3.9652014282 C -4.4287121946 1.0688555713 -1.6289742019 C 3.6412771374 -0.0731129033 2.0488206860 H -4.6366138701 2.1307065257 -1.7839553378 H 3.5887148347 -0.2853629416 3.1095693865 H -4.8076762158 0.5225024221 -2.4972939102 C 2.4285596037 0.1487833109 1.3751302798 H -3.3455035700 0.9327235399 -1.5932540558 H 2.4566870345 0.3043735058 0.3035444166 C -4.8117929897 -0.9408781074 -0.1200966765 C 1.1846357399 0.2434960376 1.9757198198 H -5.1861106891 -1.5282599535 -0.9633461578 C 0.0432642575 0.5096590008 1.1630708804 H -5.3006272287 -1.3048082295 0.7871694140 C -1.1154297610 1.1108434449 1.7399578716 H -3.7392697412 -1.1269491997 -0.0282909936 C -2.3280501886 1.0301815823 1.0824390679 C 0.6936243091 -0.7951891322 -2.2286951923 H -2.3236265731 0.4530183502 0.1655006409 H 0.5317654669 -1.6727183001 -2.8581453372 C 1.0737383681 0.2248477069 3.4871058342 H 1.7238618800 -0.4557936006 -2.3852208133 H 1.7868935278 0.9555339140 3.8902269865 C -0.2821575152 0.3480312765 -2.5160712078 H 1.3927957315 -0.7507777514 3.8756079890 H -1.2968134314 -0.0480342678 -2.6363414637 C -0.9653849778 1.6466827759 3.1420191840 H -0.0356028100 0.9148614133 -3.4163173344 H -0.3353688219 2.5457609077 3.1541923329 Cyanine-like S1 minimum H -1.9313455025 1.9340054168 3.5606381552 H 8.8374019483 -0.5097944766 2.8248571490 C -0.3244182447 0.5582544411 4.0065667918 C 8.5482131574 -0.2702379337 1.8080813653 H -0.2623936972 0.8760678802 5.0516933642 C 7.8297944575 0.3647040051 -0.8476738840 H -0.9646199935 -0.3303448906 3.9804998455 C 7.2182491157 -0.1289990760 1.4261845268 H -8.6791181929 2.6819038475 1.4860400590 C 9.5179620708 -0.0863110235 0.8280735732 C -8.3516146477 2.0123563839 0.6990459466 C 9.1704544243 0.2269151713 -0.4852725226 C -7.5367873295 0.2624108402 -1.3549531629 C 6.8553635169 0.1868104907 0.1150418108 C -7.0282668488 1.6311450463 0.5508370833 H 10.5644217741 -0.1881056638 1.0957779978 C -9.2725745901 1.4965964074 -0.2117319120 H 9.9472108627 0.3652763862 -1.2295788674 C -8.8759065369 0.6329033716 -1.2273382102 H 7.5634023623 0.6097922272 -1.8716355648 C -6.6156648301 0.7672852547 -0.4567717608 N 6.0582602125 -0.2551308154 2.1962240555 H -10.3167860995 1.7764336579 -0.1212653766 C 4.9347825438 -0.0204013581 1.4567377230 H -9.6115597428 0.2446399383 -1.9231746339 C 5.3471919244 0.2716196938 0.0150155688 H -7.2303221951 -0.4125583758 -2.1487369243 H 5.6360019579 0.2535925846 4.1916252625 C -5.1193350114 0.5481882443 -0.3547361344 C 6.0424290292 -0.5787882323 3.6075686177 C -4.7707065815 1.4032886879 0.8704091823 H 5.4316562893 -1.4689892059 3.7862844586 C -3.5519531126 1.5896893321 1.4933416771 H 7.0562245789 -0.7798585412 3.9464233217 H -3.5432856008 2.2252537711 2.3699528999 C 3.6696098614 -0.0357648344 2.0249063777 N -5.9036871536 1.9985581255 1.3203807460 H 3.6206158832 -0.2179988699 3.0924834124 N 0.0734315032 0.2179585186 -0.1870422720 C 2.4534833850 0.1831121343 1.3571681459 189 H 2.4612205258 0.3044896686 0.2812052773 C -4.8630538763 -0.9562136006 -0.1557440287 C 1.2105759254 0.3164498837 1.9818278932 H -5.2307503319 -1.5321577703 -1.0098661604 C 0.0435786596 0.5130816281 1.1909007601 H -5.3604740835 -1.3288742287 0.7431842409 C -1.1533933080 1.0431423509 1.7730389931 H -3.7915882944 -1.1435663178 -0.0571958939 C -2.3549498861 0.9783936238 1.0768288975 C 0.6611721698 -0.8112084023 -2.2026331970 H -2.3234877047 0.4273218513 0.1447683821 H 0.4586425702 -1.6777532198 -2.8359816510 C 1.1281499319 0.3450841280 3.4919321865 H 1.7062520351 -0.5204187263 -2.3601485257 H 1.7612147809 1.1661743458 3.8556915662 C -0.2576695349 0.3802202542 -2.4901528875 H 1.5623254897 -0.5725752687 3.9086903296 H -1.2892038177 0.0332947283 -2.6199059950 C -1.0470236811 1.5604599091 3.1832970452 H 0.0219464418 0.9384865266 -3.3863456529 H -0.5111803963 2.5195862696 3.2066226664 H -2.0338010867 1.7385224179 3.6146136846 Dye II-16 C -0.2898486894 0.5324959304 4.0264382198 Bis-dipole Franck-Condon Point H -0.2519384811 0.8456746127 5.0740561491 H 0.3185552181 8.4650419556 -0.9912417798 H -0.8341887635 -0.4177809630 3.9949642436 C 0.5761978977 7.9989264164 -0.0470323213 H -8.7041695105 2.6991461059 1.4960086277 C 1.2584657723 6.8235201963 2.4195157007 C -8.3842623861 2.0304327307 0.7053540514 C 0.3229424465 6.6614759404 0.2120407489 C -7.5868366643 0.2781268400 -1.3598131847 C 1.1838491590 8.7469797336 0.9610217381 C -7.0572392635 1.6397690071 0.5524383681 C 1.5237640013 8.1729953935 2.1808001183 C -9.3092352636 1.5239165161 -0.2011603548 C 0.6562801588 6.0733451311 1.4279085560 C -8.9228611859 0.6578892811 -1.2234983578 H 1.3930064399 9.7968428829 0.7840347778 C -6.6564010810 0.7720767967 -0.4665575222 H 1.9959709358 8.7752645584 2.9491869960 H -10.3517326560 1.8089005800 -0.1061959319 H 1.5241330894 6.3759703458 3.3731054906 H -9.6654535497 0.2768509535 -1.9161742253 N -0.2731750850 5.6930432600 -0.6157600295 H -7.2900725121 -0.3973836223 -2.1566993826 C -0.3502937656 4.4760140142 0.0049358467 C -5.1631475343 0.5392168753 -0.3743768539 C 0.2506131303 4.6116365528 1.4128757524 C -4.8044916086 1.3783616897 0.8515910463 H -0.5752706639 6.9785797467 -2.2206282009 C -3.5835826948 1.5398522206 1.4821109675 C -0.7472794082 5.9367025456 -1.9584294401 H -3.5753825198 2.1614519428 2.3698896671 H -0.2160454627 5.3054857848 -2.6786573074 N -5.9393506077 1.9893199212 1.3118430148 H -1.8203867469 5.7324167423 -2.0338776929 N 0.0705458554 0.2184550706 -0.1688348531 C -0.8900054350 3.3797187666 -0.6111031377 C -0.1429510372 1.2192912181 -1.2192012987 H -1.2572650063 3.5138978701 -1.6204673590 H -1.0300342772 1.8296709141 -1.0286614176 C -1.0228081855 2.0816818858 -0.0323387214 C 0.4104048484 -1.0976814845 -0.7221665441 H -0.6927823693 1.9823184073 0.9965297999 H -0.4332060784 -1.7919074295 -0.5941658433 C -1.4787150144 0.9493068105 -0.6374573641 H 1.2748314317 -1.5460048861 -0.2248562004 C -1.4327739432 -0.3240170311 0.0957597865 H 0.7151761391 1.9068825917 -1.2761892535 C -0.7457176596 -1.4197989274 -0.5837200522 C -5.9692625794 2.8792151243 2.4529978318 C 0.1708621639 -2.2022604725 0.0668260349 H -6.9726265988 3.2807204000 2.5759846042 H 0.3530484402 -1.9815989559 1.1102497657 H -5.2763276178 3.7131970680 2.3040291135 C -1.8119430070 0.8490107875 -2.1075487539 H -5.6907317908 2.3459390472 3.3680894723 H -1.7093747879 1.8228263400 -2.5876741231 C 4.8201351208 -0.7993295458 -0.9619435559 H -2.8604329247 0.5479709625 -2.2371889313 H 3.7294844595 -0.7918198984 -1.0220587657 C -0.9942761316 -1.5213348205 -2.0788837867 H 5.1404325935 -1.7998171572 -0.6602386153 H -0.2816931555 -2.2130328461 -2.5290228170 H 5.2153925652 -0.6053496226 -1.9634326200 H -1.9903118174 -1.9517508519 -2.2525262578 C 4.9142417602 1.6828822184 -0.4274397897 C -0.9051866653 -0.1726794009 -2.7900075649 H 5.2904811120 2.4424976400 0.2623696200 H 0.1290620616 0.1879114866 -2.7644553464 H 3.8272079357 1.7753345758 -0.4779990283 H -1.1852463779 -0.2883680625 -3.8419510443 H 5.3195980510 1.8970254952 -1.4205747952 H 4.5796307096 -7.0174703704 -0.8212779299 C -4.4699878952 1.0588778485 -1.6508735956 C 4.5166946200 -6.5231589781 0.1413608324 H -4.6770660250 2.1206580345 -1.8073871517 C 4.3807725544 -5.2627156018 2.6570314899 H -4.8463399953 0.5100820634 -2.5191593874 C 3.6142745937 -5.5026219179 0.3928919450 H -3.3869648693 0.9220905716 -1.6093769370 C 5.3609035727 -6.9066010598 1.1829409290 190 C 5.2987435605 -6.2884156978 2.4269305630 C 0.8185171206 6.4853979918 1.0067785182 C 3.5397923427 -4.8748378349 1.6315425630 H 0.9571693255 10.2097939194 0.0271346556 H 6.0776392817 -7.7033156369 1.0137199815 H 2.3587557714 9.3592458871 1.8695896739 H 5.9661133325 -6.6043979044 3.2212149414 H 2.2816237790 6.9654296607 2.5111229201 H 4.3336970828 -4.7807210204 3.6294024003 N -0.7246685433 5.9214590908 -0.5652963301 C 2.4620652055 -3.8086800017 1.5950498948 C -0.4511111196 4.7538809418 0.0538679253 C 1.9515245023 -3.9391216930 0.1520553150 C 0.5705767394 5.0015481001 1.1631054155 C 0.9671006526 -3.2369851330 -0.4974412711 H -1.8039212184 7.1299554577 -1.8734137145 H 0.7759142944 -3.5086018005 -1.5269904022 C -1.6602319330 6.0722752491 -1.6668916955 N 2.6597340211 -4.9269336906 -0.4680391605 H -1.2764433308 5.5836216011 -2.5667705038 N -1.9940329615 -0.4496993363 1.2985198744 H -2.6263965092 5.6380918762 -1.4012044137 C -2.9083473324 0.5658890463 1.8848611378 C -1.0352909922 3.5569120599 -0.3511111815 H -3.9287159449 0.2726582133 1.6133339659 H -1.7155940913 3.6024713388 -1.1928212444 C -1.9630300827 -1.7142792297 2.0709126691 C -0.8012048349 2.2943464033 0.2219587245 H -1.0449431149 -1.7409227707 2.6680984001 H -0.1671419948 2.2311825983 1.0978023806 H -1.9198189651 -2.5424884661 1.3625263522 C -1.3476893649 1.1079272046 -0.2189010566 H -2.7247675456 1.5315469351 1.4359426541 C -1.0317778898 -0.1804774460 0.4468258354 C 2.4504604853 -5.3215922561 -1.8430772055 C -0.1371548067 -1.0139082649 -0.2511210985 H 2.6236109502 -4.4772592977 -2.5181327958 C 0.5689207226 -2.0315291156 0.3800806042 H 1.4298981360 -5.6894252807 -1.9902611166 H 0.5197950198 -2.0419044224 1.4622480997 H 3.1448800521 -6.1180759845 -2.1019000580 C -1.9665929300 0.9041386466 -1.5574100308 C -0.7959514742 4.3522334423 2.5115520214 H -2.3677478368 1.8043705920 -2.0318505323 H -1.1030775452 3.3036559595 2.5481071990 H -2.7644708149 0.1571430863 -1.4997177203 H -1.6865545469 4.9665935389 2.3567996155 C -0.0836600264 -0.8772173717 -1.7715594921 H -0.3748953428 4.6093425339 3.4877696680 H 0.9532549413 -0.9039019440 -2.1231623370 C 1.4867520080 3.7148457895 1.5972842346 H -0.5554691922 -1.7788682186 -2.1849323642 H 2.2247263493 3.8998611168 0.8126117281 C -0.7739755387 0.3537701975 -2.3899328192 H 1.2289175926 2.6529817999 1.5773485626 H -0.0511743841 1.1693135212 -2.4975436832 H 1.9581331861 3.9300393527 2.5607423296 H -1.1256660179 0.1113038804 -3.3974017625 C 3.0770221170 -2.4232188873 1.8593952319 H 4.6484109593 -7.0583814975 -0.9039017168 H 3.8544446939 -2.1944089247 1.1260900555 C 4.4404944450 -6.7854177742 0.1245237163 H 3.5354360775 -2.4075551248 2.8524786303 C 3.9199811534 -6.1101067473 2.8075764498 H 2.3284764194 -1.6277973618 1.8209853601 C 3.5839241559 -5.7454103239 0.4543288418 C 1.3651192721 -4.1387387950 2.6229164554 C 5.0384305533 -7.4877812278 1.1702924691 H 1.7999694439 -4.1758626912 3.6257867457 C 4.7860151746 -7.1606875223 2.4978116625 H 0.9118261322 -5.1117000786 2.4163354168 C 3.3226137940 -5.4060377464 1.7806009013 H 0.5727279131 -3.3868372952 2.6290415442 H 5.7128798604 -8.3054138726 0.9373331353 C -3.1575635454 -1.8465548983 3.0074092901 H 5.2617735172 -7.7226795297 3.2941251683 H -3.0896740673 -2.8227721143 3.4957508703 H 3.7222464074 -5.8539466512 3.8447705876 H -4.0836567465 -1.8634711040 2.4236874025 C 2.3548272156 -4.2390216461 1.8249082852 C -2.7631618621 0.6166158125 3.4002888035 C 2.1216869122 -3.9791521310 0.3328594427 H -3.3714911296 1.4437276017 3.7762602141 C 1.3439626820 -3.0231302995 -0.2695665365 H -1.7234303814 0.8606377438 3.6460548226 H 1.3343225146 -3.0186082374 -1.3539875332 C -3.1823978929 -0.7194021124 4.0463885487 N 2.8610456890 -4.8895345220 -0.3877538853 H -4.1844743212 -0.6418232555 4.4768213969 N -1.7424440935 -0.5682741396 1.5697082281 H -2.5078936546 -0.9599384283 4.8736388024 C -2.3482657838 0.4300501314 2.4497031151 Bis-dipole S1 minimum H -3.1859068637 0.9482077010 1.9573339992 H -0.5463447582 8.7038273515 -1.2206936985 C -2.2433091712 -1.9437735716 1.7100822429 C 0.0577703054 8.3167858327 -0.4086459438 H -1.6706219134 -2.4941311195 2.4684389546 C 1.6599761808 7.3339431429 1.7010782268 H -2.0825764754 -2.4563778433 0.7609965198 C 0.0330631774 6.9829753280 -0.0281780977 H -1.5980954286 1.1913670507 2.6871927576 C 0.9096306849 9.1606198422 0.2970834640 C 2.8901432982 -4.9302881359 -1.8288059052 C 1.7015109936 8.6798011645 1.3384196805 H 3.2473772910 -3.9784320489 -2.2375022134 191 H 1.8923765822 -5.1312147688 -2.2346698500 C -1.8561680318 6.3658064970 -1.8200605123 H 3.5624142765 -5.7201062707 -2.1585391420 H -1.7639456209 9.7216158501 -3.7060834135 C -0.0228934501 4.7041691663 2.5549229835 H -3.3515509800 9.3924917726 -1.8444408427 H -0.2343689558 3.6415883961 2.6895287268 H -3.4177919338 7.2363760618 -0.6212742150 H -0.9475275148 5.2638327679 2.7171382285 N -0.2161222636 5.3866151358 -3.0582006437 H 0.6925646899 5.0052135697 3.3246360599 C -0.5650515535 4.4221456418 -2.1709074249 C 1.8750036644 4.2161367901 0.9278769231 C -1.6723043698 4.9688836073 -1.2617047735 H 2.2878782855 4.4228808447 -0.0629166019 H 0.8675723477 6.1241793357 -4.6747482342 H 1.7264454558 3.1389429280 1.0197493593 C 0.7972353410 5.2168007238 -4.0790796111 H 2.6171599084 4.5184558649 1.6712775911 H 1.7730715182 5.0196535897 -3.6252868209 C 3.0066822190 -3.0319062880 2.5220883236 H 0.5373621617 4.3852122241 -4.7407914769 H 3.9258880641 -2.7355175027 2.0100169343 C 0.0367174903 3.1785079557 -2.1770853604 H 3.2632433475 -3.2937754134 3.5529581450 H 0.8003564854 3.0130872745 -2.9262566945 H 2.3377818852 -2.1686867874 2.5475593380 C -0.2434912258 2.1098847285 -1.3040614710 C 1.0580719035 -4.6542314940 2.5433573522 H -0.9591831552 2.2759027419 -0.5099735809 H 1.2812393432 -4.9368104845 3.5764414243 C 0.2825537390 0.8361190249 -1.4165213533 H 0.5970037945 -5.5131228158 2.0492725950 C -0.0730668551 -0.1756706385 -0.4677423779 H 0.3304306552 -3.8398436480 2.5640328583 C 0.0078984991 -1.5532589242 -0.8680119966 C -3.7209912600 -1.9387759346 2.0898100957 C 0.2991850550 -2.5250171018 0.0631569421 H -4.0970316015 -2.9663963571 2.0998146359 H 0.4329473533 -2.1835901631 1.0809661275 H -4.2764598054 -1.4109925410 1.3060495119 C 1.1108968536 0.4840920428 -2.6416178959 C -2.8448933560 -0.2234910057 3.7351036953 H 2.0844744723 0.9891071521 -2.5984172942 H -3.2071272478 0.5525128540 4.4157530735 H 0.5986456617 0.8984437916 -3.5181954362 H -1.9915001441 -0.6997479065 4.2298340844 C 0.0915236639 -1.7898992693 -2.3546735764 C -3.9442231284 -1.2605890689 3.4532768604 H 0.1864265491 -2.8509559423 -2.5873468806 H -4.9286037564 -0.7824873832 3.4698232136 H -0.8123524576 -1.4330919123 -2.8635128178 H -3.9494267672 -2.0065310035 4.2537779902 C 1.3119649366 -1.0181603477 -2.8633834715 Cyanine-like Franck-Condon Point H 2.1957674703 -1.3761155330 -2.3248834369 H -0.2234359147 7.9225059394 -4.3912593911 H 1.4866657319 -1.2105391948 -3.9264127561 C -0.9130857608 7.7603076986 -3.5708820058 H 1.8770626329 -8.8769496660 0.7280175574 C -2.7185097432 7.3767786772 -1.4402897117 C 2.0124987742 -8.2028988916 1.5661223364 C -0.9717935218 6.5649240167 -2.8735969833 C 2.3809464988 -6.4796418549 3.7650586885 C -1.7866237334 8.7736817190 -3.1789375489 C -2.6804391639 8.5895560946 -2.1292052161 C 1.6849643704 -6.8587235007 1.4981662374 C 0.8364786646 -6.6883959355 -0.8774518885 C 2.5353753405 -8.6759510415 2.7688937752 H 1.4644452940 -6.2427764254 -1.6557622246 C 2.7187671963 -7.8303411852 3.8577100832 H -0.2146141904 -6.5151244223 -1.1263417512 C 1.8639555829 -5.9998914882 2.5765278222 H 1.0143847613 -7.7614528301 -0.8599728305 H 2.8034173066 -9.7240789529 2.8506619657 C -2.9745323169 4.1611015624 -1.4000255216 H 3.1273910529 -8.2219359676 4.7828027270 H -2.8647790144 3.1426130502 -1.0199205217 H 2.5271879139 -5.8212873935 4.6164754620 H -3.2919231101 4.1033870395 -2.4442627885 C 1.4177977867 -4.6030647764 2.1918487470 H -3.7709309554 4.6505744386 -0.8322892869 C 0.9793278764 -4.8147344361 0.7358601625 C -1.2171998475 5.0466072202 0.2068327887 C 0.5072585820 -3.9008104142 -0.1807183351 H -0.2701743149 5.5841588920 0.2999196947 H 0.2954342934 -4.2709067249 -1.1756068079 H -1.0938939414 4.0543229215 0.6459569514 N 1.1489595689 -6.1262167117 0.4190817497 H -1.9682615717 5.5822705847 0.7940975242 N -0.4868052983 0.1546882191 0.7934999943 C 2.5966921021 -3.6198835739 2.2991839855 C 0.1358909131 1.2405255724 1.5748666065 H 3.4305556613 -3.9351661949 1.6666523454 H -0.3937330207 2.1914709595 1.4557404825 H 2.9520882958 -3.5862436792 3.3331256823 C -1.5754809092 -0.5753235430 1.4768319573 H 2.3108183296 -2.6066475554 2.0065205315 H -1.2073039469 -1.4428138992 2.0338911473 C 0.2442408690 -4.1650369903 3.0869098241 H -2.2592816301 -0.9512712771 0.7132077837 H 0.5578315056 -4.1851078715 4.1343715695 H 1.1499161017 1.3861675771 1.1984854649 H -0.6089770234 -4.8390949699 2.9764998348 192 H -0.0881302441 -3.1496790626 2.8581460458 C -1.0864761558 6.6007738491 -2.8438983473 C -2.2814011767 0.3555016427 2.4563553902 C -1.9273816778 8.8117549104 -3.0730976159 H -3.1530226766 -0.1599856352 2.8695975855 C -2.7456892274 8.6156288598 -1.9614177099 H -2.6657590663 1.2254128376 1.9119105338 C -1.8996143789 6.3899590702 -1.7282055286 C 0.1249296028 0.8723732759 3.0543586456 H -1.9465407007 9.7649049975 -3.5904514812 H 0.7028267743 1.6143864622 3.6126874792 H -3.3934559127 9.4166429227 -1.6227917231 H 0.6384067787 -0.0866070664 3.1874202690 H -3.3750282819 7.2475690893 -0.4181769107 C -1.3213357743 0.7944828568 3.5766658617 N -0.3480432475 5.4392678253 -3.0880180775 H -1.6355290388 1.7675211643 3.9662502655 C -0.6366953434 4.4581751154 -2.1829797967 H -1.3731294378 0.0940934430 4.4158605683 C -1.6767936222 4.9890492954 -1.1983491148 Cyanine-like S1 minimum H 0.6574346424 6.2112052452 -4.7392176233 H -0.4568018528 7.9781395612 -4.4031659099 C 0.5933543802 5.2824987539 -4.1767803597 C -1.0832605870 7.8074433570 -3.5351533245 H 1.5880168508 5.0387386258 -3.7910126013 C -2.7345797306 7.3963131153 -1.2824803274 H 0.2697962090 4.4845932893 -4.8530558689 C -0.0388628104 3.2077244838 -2.2508311870 H 1.3486431884 1.1578171535 1.1664018639 H 0.6575316326 3.0543414014 -3.0671871144 C 0.9122773029 -6.7158282114 -0.7933179012 C -0.2485273271 2.1226078715 -1.3848567924 H 1.6027778231 -6.3199892485 -1.5456988581 H -0.8994768444 2.2507350979 -0.5300735415 H -0.1136312883 -6.4920988164 -1.1015440284 C 0.2818184531 0.8409291602 -1.5735486265 H 1.0315996096 -7.7958552702 -0.7458839200 C 0.0457508095 -0.1811563794 -0.6153946646 C -2.9863453036 4.1772693873 -1.2582639226 C 0.2583233102 -1.5618502115 -0.9613365791 H -2.8423847202 3.1531952768 -0.9062473771 C 0.4667892902 -2.5068468190 0.0316394406 H -3.3779544419 4.1379079025 -2.2780682600 H 0.5186767121 -2.1196920018 1.0413117079 H -3.7411501263 4.6514213941 -0.6245302348 C 1.0347555217 0.5349320806 -2.8525488401 C -1.1285317277 5.0422969668 0.2416315505 H 1.9065305439 1.1956750929 -2.9413356127 H -0.2019781873 5.6203096647 0.2903693217 H 0.3818582285 0.7888981830 -3.6983208576 H -0.9292033318 4.0420641102 0.6318453619 C 0.4079203615 -1.8596903918 -2.4289465894 H -1.8625447796 5.5209516495 0.8962853223 H 0.6923569342 -2.8983851389 -2.6047289239 C 2.5751471719 -3.6296614341 2.4467777494 H -0.5403211337 -1.6922195492 -2.9568895283 H 3.4434970724 -3.9696802580 1.8769076623 C 1.4790392254 -0.9208030280 -2.9896901586 H 2.8583048813 -3.5863868099 3.5025064004 H 2.4118456879 -1.0865932641 -2.4396616280 H 2.3271751181 -2.6169839000 2.1206638485 H 1.6816943272 -1.1469498612 -4.0411268287 C 0.1682126404 -4.1040769881 3.0872125763 H 1.8114210408 -8.9023419689 0.8806787081 H 0.4237650067 -4.0942057820 4.1507805313 C 1.9120921823 -8.2229357561 1.7190085293 H -0.6907415533 -4.7658681004 2.9510175136 C 2.1940790290 -6.4763809620 3.9191604618 H -0.1274228645 -3.0915267636 2.8030756437 C 1.6269809658 -6.8647475811 1.6132613318 C -2.2044368927 0.4211513708 2.2924104470 C 2.3430012315 -8.6924533693 2.9545440749 H -3.1414114707 -0.0168362055 2.6493137721 C 2.4842404077 -7.8358605495 4.0459449308 H -2.4653873502 1.3826759469 1.8346768057 C 1.7667257178 -5.9941075372 2.6976003247 C 0.2364261497 0.6578667946 2.9653871888 H 2.5732172552 -9.7464125356 3.0679085501 H 0.8452278852 1.3234405515 3.5845962759 H 2.8222313371 -8.2295860213 4.9981511177 H 0.6853025297 -0.3394726617 3.0452678695 H 2.3070386564 -5.8134208011 4.7719106800 C -1.2243941288 0.6313611274 3.4592065158 C 1.3834038627 -4.5919449638 2.2722864772 H -1.4679354388 1.5655445551 3.9744286030 C 1.0338667077 -4.8105156438 0.7998970300 H -1.3457656076 -0.1674545465 4.1980670217 C 0.6552718423 -3.8940912034 -0.1619639464 H 0.4967265483 -4.2791982405 -1.1624471658 N 1.1816195971 -6.1411601256 0.5074561695 N -0.3971804501 0.1413510146 0.6626083539 C 0.3121889783 1.1057639938 1.5086524411 H -0.0979229783 2.1225928138 1.4315281842 C -1.6014573647 -0.4858588444 1.2250308420 H -1.3976368993 -1.4679508276 1.6736759654 H -2.3129881353 -0.6544083471 0.4116102886 193 REFERENCES (1) Rathore, N.; Panwar, N. L.; Yettou, F.; Gama, A. A comprehensive review of different types of solar photovoltaic cells and their applications. International Journal of Ambient Energy 2021, 42 (10), 1200-1217. DOI: 10.1080/01430750.2019.1592774. (2) Husain, A. A. F.; Hasan, W. Z. W.; Shafie, S.; Hamidon, M. N.; Pandey, S. S. A review of transparent solar photovoltaic technologies. Renew Sust Energ Rev 2018, 94, 779-791. DOI: 10.1016/j.rser.2018.06.031. (3) Traverse, C. J.; Pandey, R.; Barr, M. C.; Lunt, R. R. Emergence of highly transparent photovoltaics for distributed applications. Nat Energy 2017, 2 (11). DOI: 10.1038/s41560-017-0016-9. (4) Yang, C. C.; Lunt, R. R. Limits of Visibly Transparent Luminescent Solar Concentrators. Adv Opt Mater 2017, 5 (8). DOI: ARTN 160085110.1002/adom.201600851. (5) Sharma, M.; Gungor, K.; Yeltik, A.; Olutas, M.; Guzelturk, B.; Kelestemur, Y.; Erdem, T.; Delikanli, S.; McBride, J. R.; Demir, H. V. Near-Unity Emitting Copper- Doped Colloidal Semiconductor Quantum Wells for Luminescent Solar Concentrators. Adv Mater 2017, 29 (30). DOI: ARTN 170082110.1002/adma.201700821. (6) Ooyama, Y.; Harima, Y. Photophysical and Electrochemical Properties, and Molecular Structures of Organic Dyes for Dye-Sensitized Solar Cells. Chemphyschem 2012, 13 (18), 4032-4080. DOI: 10.1002/cphc.201200218. (7) Yang, C. In PhD Thesis “HIGH-PERFORMANCE VISIBLY TRANSPARENT LUMINESCENT SOLAR CONCENTRATORS”. Michigan State University 2022. (8) Zhao, Y.; Lunt, R. R. Transparent Luminescent Solar Concentrators for Large-Area Solar Windows Enabled by Massive Stokes-Shift Nanocluster Phosphors. Adv Energy Mater 2013, 3 (9), 1143-1148. DOI: 10.1002/aenm.201300173. (9) Kuttipillai, P. S.; Yang, C. C.; Chen, P.; Wang, L. L.; Bates, M.; Lunt, S. Y.; Lunt, R. R. Enhanced Electroluminescence Efficiency in Metal Halide Nanocluster Based Light Emitting Diodes through Apical Halide Exchange. Acs Appl Energ Mater 2018, 1 (8), 3587-3592. DOI: 10.1021/acsaem.8b00837. (10) Sun, W.; Guo, S. G.; Hu, C.; Fan, J. L.; Peng, X. J. Recent Development of Chemosensors Based on Cyanine Platforms. Chem Rev 2016, 116 (14), 7768- 7817. DOI: 10.1021/acs.chemrev.6b00001. 194 (11) Samanta, A.; Vendrell, M.; Das, R.; Chang, Y. T. Development of photostable near- infrared cyanine dyes. Chem Commun 2010, 46 (39), 7406-7408. DOI: 10.1039/c0cc02366c. (12) Davydenko, I.; Barlow, S.; Sharma, R.; Benis, S.; Simon, J.; Allen, T. G.; Cooper, M. W.; Khrustalev, V.; Jucov, E. V.; Castaneda, R.; et al. Facile Incorporation of Pd(PPh3)(2)Hal Substituents into Polymethines, Merocyanines, and Perylene Diimides as a Means of Suppressing Intermolecular Interactions. J Am Chem Soc 2016, 138 (32), 10112-10115. DOI: 10.1021/jacs.6b06361. (13) Zhao, Y. M.; Meek, G. A.; Levine, B. G.; Lunt, R. R. Near-Infrared Harvesting Transparent Luminescent Solar Concentrators. Adv Opt Mater 2014, 2 (7), 606- 611. DOI: 10.1002/adom.201400103. (14) Yang, C. C.; Zhang, J.; Peng, W. T.; Sheng, W.; Liu, D. Y.; Kuttipillai, P. S.; Young, M.; Donahue, M. R.; Levine, B. G.; Borhan, B.; et al. Impact of Stokes Shift on the Performance of Near-Infrared Harvesting Transparent Luminescent Solar Concentrators. Sci Rep-Uk 2018, 8. DOI: ARTN 1635910.1038/s41598-018- 34442-3. (15) Peng, X. J.; Song, F. L.; Lu, E.; Wang, Y. N.; Zhou, W.; Fan, J. L.; Gao, Y. L. Heptamethine cyanine dyes with a large stokes shift and strong fluorescence: A paradigm for excited-state intramolecular charge transfer. J Am Chem Soc 2005, 127 (12), 4170-4171. DOI: 10.1021/ja043413z. (16) Pascal, S.; Haefele, A.; Monnereau, C.; Charaf-Eddin, A.; Jacquemin, D.; Le Guennic, B.; Andraud, C.; Maury, O. Expanding the Polymethine Paradigm: Evidence for the Contribution of a Bis-Dipolar Electronic Structure. J Phys Chem A 2014, 118 (23), 4038-4047. DOI: 10.1021/jp501358q. (17) Das, R. K.; Samanta, A.; Ha, H. H.; Chang, Y. T. Solid phase synthesis of ultra- photostable cyanine NIR dye library. Rsc Adv 2011, 1 (4), 573-575. DOI: 10.1039/c1ra00498k. (18) Le Guennic, B.; Jacquemin, D. Taking Up the Cyanine Challenge with Quantum Tools. Accounts Chem Res 2015, 48 (3), 530-537. DOI: 10.1021/ar500447q. (19) Bassal, F.; Laurent, A. D.; Le Guennic, B.; Jacquemin, D. Exploring the excited- states of squaraine dyes with TD-DFT, SOS-CIS(D) and ADC(2). Dyes Pigments 2017, 138, 169-175. DOI: 10.1016/j.dyepig.2016.11.046. (20) Yanai, T.; Tew, D. P.; Handy, N. C. A new hybrid exchange-correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chem Phys Lett 2004, 393 (1-3), 51-57. DOI: 10.1016/j.cplett.2004.06.011. 195 (21) Ufimtsev, I. S.; Martinez, T. J. Quantum Chemistry on Graphical Processing Units. 3. Analytical Energy Gradients, Geometry Optimization, and First Principles Molecular Dynamics. J Chem Theory Comput 2009, 5 (10), 2619-2628. DOI: 10.1021/ct9003004. (22) Isborn, C. M.; Luehr, N.; Ufimtsev, I. S.; Martinez, T. J. Excited-State Electronic Structure with Configuration Interaction Singles and Tamm-Dancoff Time- Dependent Density Functional Theory on Graphical Processing Units. J Chem Theory Comput 2011, 7 (6), 1814-1823. DOI: 10.1021/ct200030k. (23) Liu, X. G.; Xu, Z. C.; Cole, J. M. Molecular Design of UV-vis Absorption and Emission Properties in Organic Fluorophores: Toward Larger Bathochromic Shifts, Enhanced Molar Extinction Coefficients, and Greater Stokes Shifts. J Phys Chem C 2013, 117 (32), 16584-16595. DOI: 10.1021/jp404170w. (24) Siebert, M. R.; Tantillo, D. J. Fundamental properties of N-alkenylaziridines- implications for the design of new reactions and organocatalysts. J Phys Org Chem 2011, 24 (6), 445-449. DOI: 10.1002/poc.1776. (25) Dong, V. M.; Fiedler, D.; Carl, B.; Bergman, R. G.; Raymond, K. N. Molecular recognition and stabilization of iminium ions in water. J Am Chem Soc 2006, 128 (45), 14464-14465. DOI: 10.1021/ja0657915. (26) Zhang, J.; Moemeni, M.; Yang, C. C.; Liang, F. C.; Peng, W. T.; Levine, B. G.; Lunt, R. R.; Borhan, B. General strategy for tuning the Stokes shifts of near infrared cyanine dyes. J Mater Chem C 2020, 8 (47), 16769-16773. DOI: 10.1039/d0tc03615c. (27) Zhang, Q.; Kan, B.; Liu, F.; Long, G. K.; Wan, X. J.; Chen, X. Q.; Zuo, Y.; Ni, W.; Zhang, H. J.; Li, M. M.; et al. Small-molecule solar cells with efficiency over 9%. Nat Photonics 2015, 9 (1), 35-41. DOI: 10.1038/Nphoton.2014.269. (28) Xiao, Z.; Jia, X.; Ding, L. M. Ternary organic solar cells offer 14% power conversion efficiency. Sci Bull 2017, 62 (23), 1562-1564. DOI: 10.1016/j.scib.2017.11.003. (29) Meng, L. X.; Zhang, Y. M.; Wan, X. J.; Li, C. X.; Zhang, X.; Wang, Y. B.; Ke, X.; Xiao, Z.; Ding, L. M.; Xia, R. X.; et al. Organic and solution-processed tandem solar cells with 17.3% efficiency. Science 2018, 361 (6407), 1094-+. DOI: 10.1126/science.aat2612. (30) Xiao, Z.; Jia, X.; Li, D.; Wang, S. Z.; Geng, X. J.; Liu, F.; Chen, J. W.; Yang, S. F.; Russell, T. P.; Ding, L. M. 26 mA cm(-2) J(sc) from organic solar cells with a low- bandgap nonfullerene acceptor. Sci Bull 2017, 62 (22), 1494-1496. DOI: 10.1016/j.scib.2017.10.017. 196 (31) Wang, J. Y.; Zhang, J. X.; Xiao, Y. Q.; Xiao, T.; Zhu, R. Y.; Yan, C. Q.; Fu, Y. Q.; Lu, G. H.; Lu, X. H.; Marder, S. R.; et al. Effect of Isomerization on High- Performance Nonfullerene Electron Acceptors. J Am Chem Soc 2018, 140 (29), 9140-9147. DOI: 10.1021/jacs.8b04027. (32) Yang, C. H.; Moemeni, M.; Bates, M.; Sheng, W.; Borhan, B.; Lunt, R. R. High- Performance Near-Infrared Harvesting Transparent Luminescent Solar Concentrators. Adv Opt Mater 2020, 8 (8). DOI: ARTN 190153610.1002/adom.201901536. (33) Liu, G. J.; Zhao, H. G.; Diao, F. Y.; Ling, Z. B.; Wang, Y. Q. Stable tandem luminescent solar concentrators based on CdSe/CdS quantum dots and carbon dots. J Mater Chem C 2018, 6 (37), 10059-10066. DOI: 10.1039/c8tc02532k. (34) Mateen, F.; Ali, M.; Lee, S. Y.; Jeong, S. H.; Ko, M. J.; Hong, S. K. Tandem structured luminescent solar concentrator based on inorganic carbon quantum dots and organic dyes. Sol Energy 2019, 190, 488-494. DOI: 10.1016/j.solener.2019.08.045. (35) Liu, C.; Li, B. Multiple dyes containing luminescent solar concentrators with enhanced absorption and efficiency. J Optics-Uk 2015, 17 (2). DOI: Artn 02590110.1088/2040-8978/17/2/025901. (36) Banal, J. L.; Zhang, B. L.; Jones, D. J.; Ghiggino, K. P.; Wong, W. W. H. Emissive Molecular Aggregates and Energy Migration in Luminescent Solar Concentrators. Accounts Chem Res 2017, 50 (1), 49-57. DOI: 10.1021/acs.accounts.6b00432. (37) Zhang, B. L.; Banal, J. L.; Jones, D. J.; Tang, B. Z.; Ghiggino, K. P.; Wong, W. W. H. Aggregation-induced emission-mediated spectral downconversion in luminescent solar concentrators. Mater Chem Front 2018, 2 (3), 615-619. DOI: 10.1039/c7qm00598a. (38) Goetzberger, A.; Greubel, W. Solar-Energy Conversion with Fluorescent Collectors. Appl Phys 1977, 14 (2), 123-139. DOI: Doi 10.1007/Bf00883080. (39) Kirakci, K.; Kubat, P.; Dusek, M.; Fejfarova, K.; Sicha, V.; Mosinger, J.; Lang, K. A Highly Luminescent Hexanuclear Molybdenum Cluster - A Promising Candidate toward Photoactive Materials. Eur J Inorg Chem 2012, (19), 3107-3111. DOI: 10.1002/ejic.201200402. (40) Sarma, T.; Panda, P. K.; Setsune, J. Bis-naphthobipyrrolylmethene derived BODIPY complex: an intense near-infrared fluorescent dye. Chem Commun 2013, 49 (84), 9806-9808. DOI: 10.1039/c3cc44834g. (41) Yang, C. C.; Sheng, W.; Moemeni, M.; Bates, M.; Herrera, C. K.; Borhan, B.; Lunt, R. R. Ultraviolet and Near-Infrared Dual-Band Selective-Harvesting Transparent 197 Luminescent Solar Concentrators. Adv Energy Mater 2021, 11 (12). DOI: ARTN 200358110.1002/aenm.202003581. (42) Michie, M. S.; Gotz, R.; Franke, C.; Bowler, M.; Kumari, N.; Magidson, V.; Levitus, M.; Loncarek, J.; Sauer, M.; Schnermann, M. J. Cyanine Conformational Restraint in the Far-Red Range. J Am Chem Soc 2017, 139 (36), 12406-12409. DOI: 10.1021/jacs.7b07272. (43) Matikonda, S. S.; Hammersley, G.; Kumari, N.; Grabenhorst, L.; Glembockyte, V.; Tinnefeld, P.; Ivanic, J.; Levitus, M.; Schnermann, M. J. Impact of Cyanine Conformational Restraint in the Near-Infrared Range. J Org Chem 2020, 85 (9), 5907-5915. DOI: 10.1021/acs.joc.0c00236. (44) Yang, Q. L.; Ma, Z. R.; Wang, H. S.; Zhou, B.; Zhu, S. J.; Zhong, Y. T.; Wang, J. Y.; Wan, H.; Antaris, A.; Ma, R.; et al. Rational Design of Molecular Fluorophores for Biological Imaging in the NIR-II Window. Adv Mater 2017, 29 (12). DOI: ARTN 160549710.1002/adma.201605497. 198 Chapter III: Discovery of a Novel Cyanine Degradation Pathway 199 III-1 Introduction to cyanine fluorescent dyes Organic fluorescent dyes have grown to be instrumental in applications including but not limited to: cellular biology, biomedical drug design, advanced materials engineering, as well as energy capture/conversion.1-8 The ability to synthetically tune structure and in turn, photophysical properties of a chromophore to suit a particular application, are crucial to the continuation of the growth of the field. Among one of the most widely utilized chromophores, cyanine dyes, have caught the attention of many different disciplines, due to their unique structural characteristics.9-12 Cyanines in particular boast a high relative brightness, and have significant advantages as a result of their ease of synthetic tunability, as well as an electronic push-pull structure that gives them the absorption and emission wavelength ranging from ultraviolet (UV) to deep far- red. Cyanine dyes are typically classed based on the number of methine carbons between the two indolinium based heterocyclic units connecting the methine chain (Figure III-1). 2 4 6 N 3 5 7 N 1 I Cy7 2 4 2 N N N N I 1 3 5 I 1 3 Cy5 Cy3 Figure III-1. Structure of famous cyanine dyes 200 In general, the monomethine (Cy1) and trimethine (Cy3) cyanines absorb and emit light in the UV to visible range of the spectrum, while pentamethine (Cy5) and heptamethine (Cy7) cyanines absorb and emit in the near infrared region (NIR). More specifically, pentamethine and heptamethine cyanines find a diverse range of applications both for in vivo imaging and photodynamic therapy owing to their NIR spectrum profile displaying deep tissue penetration with minimal autofluorescence.4, 13-17 Additionally, the NIR cyanines (Cy5 & Cy7) have become a focus for solar energy harvesting, as a result of a high flux of solar radiation in this region of the spectrum.2, 7, 18-21 III-2 Photo-degradation pathways of cyanine dyes The stability of the cyanine fluorophores however, tends to suffer as a result of the reactivity of their methine backbone with other reactive species. In particular, the oxidative degradation of cyanines involving singlet oxygen has been of intense interest in the last decades and different studies have reported the oxidative cleavage of the methine chain to yield carbonyl containing fragments (Figure III-2).22-24 O2, h𝒗 R O R R R N O N n N n n N X R R R R X III-1 III-2 III-3 n = 1, 2, or 3 n = 1 or 2 n = 0 or 1 Figure III-2. Cyanine photolysis products As shown in Figure III-3, in 2015, Schnermann and co-workers25 reported an experimental and theoretical study on the photooxidative cleavage of heptamethine cyanines. The degraded fragments of this reaction were identified via mass spectroscopy, 201 demonstrating that the photolysis products were obtained only in the presence of a source of singlet oxygen (generated chemically or via photosensitization). O N O N I h𝒗 III-4 III-5 N N I Cy7 O N O N I III-6 III-7 N N O I O III-8 N N O I O III-9 Figure III-3. Mechanism and degradation products of cyanine photooxidation Understanding the basis of cyanines degradation through photooxidation has opened development of novel methods. Recent literature reports highlight the photooxidative degradation process of heptamethine cyanines as the critical step for a NIR uncaging strategy relevant for biological studies.26 Alternatively, the oxidative cleavage of cyanines with respect to a reactive singlet oxygen (RSO) species, has led to the development of NIR fluorescent probes.27, 28 In more recent advancements, a phenomenon defined as “photoblueing” takes place through selective photodegradation using various wavelengths of light, cleaving away smaller cyanine fragments, demonstrating potential applications in super-resolution imaging and single-particle 202 tracking.29-31 This blue shifting effect is the result of phototruncation of two methine carbons from the cyanine’s unsaturated backbone, initiated by a singlet oxygen species (Figure III-4). h𝒗 N N N N I I Cy5 Cy3 Figure III-4. Photoblueing results from two carbon truncation In 2021, Schnermann and co-workers proposed a detailed mechanism for this transformation.32 As shown in Figure III-5, This mechanism initiates with attack by singlet oxygen to the C1 position of Cy5 to generate a peroxy intermediate III-10 which as described before, could generate fragments III-4 and III-7 (path A) or carry out a hydration to yield the hydroperoxyethanol III-11 (path B). Attack from the uncharged nitrogen to the iminium side, led to the formation of a four member intermediate in III-12. Elimination of hydroperoxyethenol in the final step resulted in a truncated trimethine cyanine as the final product. Initially, the isolated yield of the photo-truncated cyanine (Cy5) in this reaction was less than 2%, however, in this recently published report, investigators optimized the reaction increasing the pH to 9.5 and improving the yield to 17.2%. 203 O N O N N N I O III-4 III-7 O III-13 Path A 1O H 2O 2 Path B N N N N I Cy5 O O III-10 HOO OH HO OOH OH N N N N I O III-12 OH III-11 N N I Cy3 Figure III-5. Photodegradation mechanism (by Schnermann and co-workers) A separate published work by Lee and co-workers in the same year, applied the cyanine photoconversion for single-particle tracking in a living cell.33 In this study, they showed another mechanistic approach to cyanine phototruncation. As shown in Figure III-6, the carbonyl products III-14 and III-15 were formed through the previously described mechanism. The conversion of these aldehydes to their respective Fischer base III-16 is not clear, however they hypothesized a retro-aldol-type carbon−carbon bond cleavage or 204 a ROS-mediated decarbonylation. The subsequent condensation of the Fisher base III- 16 with another aldehyde III-15 provides the Cy3 product. O3S SO3 O3S SO3 h𝒗 retro-aldol or O2 O decarbonylation N N N O N I I R R R R III-14 III-15 Cy5 SO3 O3S SO3 O3S SO3 H 2O III-15 OH N N N N N I I R III-16 III-17 Cy3 Figure III-6. Photodegradation mechanism (by Lee and co-workers) III-3 Discovery and development of a non-photoactivated, oxygen-free degradation of cyanine dyes III-3-1 An observation leads to novel cyanine degradation pathway As described in Chapter II, we previously reported a general strategy to tune heptamethine cyanine’s photophysical properties (Stokes shift) through the C4′- substitution of an existing halogen with a variety of structurally diverse amines34 (Figure III-7a). In subsequent studies used to supplement the initial findings, we attempted to synthetically access the C3′ (asymmetric) position, but to our surprise, instead of the expected aminated cyanine product, we observed truncation of the parent Cy7 heptamethine cyanine, to yield Cy5 and AsCy5 as the primary species (Figure III-7b). 205 A. Reaction for amination at C4′ position R2NH R R X N DIPEA N N ACN, heat N N I I III-18 III-19 B. Reaction for amination at C3′ position N N I Et2NH Br DIPEA C3′-Br-Cy5 N N ACN, heat m/z: 461.1590 I Br C3′-Br-Cy7 Et N N Br Et I As-Br-Cy5 m/z: 387.1438 Figure III-7. A. Amination at C4′ for tuning the Stokes shift, B. Amination at C3′ resulted in corresponding Cy5 and As-Cy5 derivatives These findings inspired us to investigate the working mechanism of this two-carbon truncation that converts the parent Cy7 to symmetrical Cy5 and smaller products. As outlined below, the heterocyclic indolinium “head groups”, can be exchanged between dyes in the truncation process. Via separation and spectroscopic identification of key degradation products as well as synthesis of cyanines labeled with deuterium atoms we developed insight into the nature of the degradation pathways. This work is the first study of non-photoactivated, anaerobic, thermally driven degradation of a commonly utilized class of cyanines. The truncation reaction is also a practical and novel method for the conversion of heptamethine cyanine dyes to their corresponding symmetric and asymmetric pentamethine cyanine derivatives with high efficiency. 206 III-3-2 Identification and optimization of degradation products The heptamethine cyanines Cy7 and C3′-bromo substituted Cy7 (C3′-Br-Cy7) were synthesized according to the procedure reported by Klan and co-workers35 (Figure III-8). The Zincke salts were generated from substituted pyridine and react with heterocycle head groups to make the cyanines. X X OTs OTs N N N I NO2 NO2 X = H, Br 4-Bromoaniline, NaOAc Toluene, 110℃, 16 h MeOH, rt 16 h NO2 NO2 III-20 III-21 N N I X Cy7 (X = H) C3′-Br-Cy7 (X = Br) Figure III-8. General synthesis of heptamethine cyanines As shown in Figure III-7B, we initially observed this two carbon truncation while attempting the amination of the asymmetrically halogenated heptamethane cyanines (C3′-Br-Cy7), by subjecting them to previously employed methods: nucleophilic addition of an amine under basic conditions, (NHEt2 – 10 equiv, DIPEA – 2 equiv, at 70 ºC for 24 h). Upon the reaction of the C3′-Br-Cy7 under these conditions, we observed two compounds with the mass of m/z: 461.1590 and m/z: 387.1438 corresponding to C3′-Br- Cy5 and As-Br-Cy5, respectively (Figure III-7B). These fragments were subsequently isolated as the main products and their structures were assigned based on NMR and 207 Mass spectroscopies. Notably, apparent dehalogenation of C3′-Br-Cy7 to Cy7 was also observed under these conditions. For further studies, we chose heptamethine (Cy7) in order to establish a generalized approach for our degradation studies. Degradation of Cy7 under the abovementioned conditions led to fragments with observed masses of m/z: 383.2477 for Cy5 and m/z: 309.2327 for AsCy5. These were obtained as primary degradation products (Figure III-9). N N I Et2NH Cy5 DIPEA m/z: 383.2477 N N ACN, heat I Cy7 Et N N Et I AsCy5 m/z: 309.2327 Figure III-9. Study the conversions on Cy7 to investigate the generality of this reaction These findings led us to investigate a series of reaction conditions using Cy7 to better comprehend the role of each of the reaction parameters in this unique transformation. All reactions were degassed and run in the dark under. Argon atmosphere. First, we omitted the tertiary amine (DIPEA) and ran the reaction using only 10 equivalents of diethylamine. These results are summarized in Table III-1. Interestingly, not only we saw a change in the ratio of AsCy5/ Cy5 (2.75:1) but also an improvement in the yield of the previously isolated AsCy5 (Table III-1, entry 2). Next, we lowered the temperature from 70 ºC to room temperature. The same products were formed but more 208 slowly and in a ratio of AsCy5/ Cy5 (3.3:1). Extending the reaction time we were able to achieve a yield of 41% for AsCy5 (Table III-1, entry 3). Table III-1. Reaction optimization with secondary amine N N R2NH, R3N I Cy5 N N ACN I temp., time Cy7 Et N N AsCy5 Et I Entrya Secondary Amine Tertiary Amine Temp. Time Product (yield %) DIPEA 1 Et2N (10 equiv.) 70 °C 60 h Cy5 (11), AsCy5 (24) (2 equiv.) 2 Et2N (10 equiv.) - 70 °C 60 h Cy5 (12), AsCy5 (33) 3 Et2N (10 equiv.) - r.t. 160 h Cy5 (17), AsCy5 (41) Cy5 (11), M-As-Cy5 4 Morpholine (10 equiv.) - r.t. 20 h (40) [a] The reactions was done in sealed tube, under argon, and followed by LC-MS. Increasing the reaction time also led interestingly to the conversion of AsCy5 to AsCy3 and subsequently to AsCy1 (Figure III-10). The degradation products AsCy5, AsCy3 and AsCy1 were isolated and characterized by NMR and mass spectroscopy. As discussed above, the conversion of Cy7 to AsCy5 is higher yielding at room temperature. At higher temperatures, AsCy5 converts to smaller fragments AsCy3 and AsCy1 faster, reducing the isolated yield of AsCy5. As shown in Figure III-10 (dashed box), there were two hypothesized key fragments III-22 and III-23 that were present in the crude reaction mass, but were not isolable presumably due to their limited formation, and/or instability 209 during purification. The structures were hypothesized according to the mass of the compounds. Et2NH ACN, heat Et N N N N I Cy7 AsCy5 Et I continue heating other degraded species Et N N N N AsCy3 Et I I Cy5 continue heating N N I Et III-22 III-23 N N I AsCy1 Et Figure III-10. Identified compounds from cyanine truncation with secondary amine To extend the generality of our method, we additionally studied a variety of secondary amines. For instance, as listed in Table III-1 (entry 4), when the amine was changed to morpholine we successfully isolated and characterized the corresponding M- As-Cy5 and M-As-Cy3 (Reaction details in the experimental section). In summary, use of a 2° amine instead of a 3° amine, along with decreasing the temperature to room temperature with longer reaction time, improved the yield of AsCy5. On the other hand, under identical conditions at higher temperature, AsCy5 converts to the smaller fragments AsCy3 and AsCy1 with a higher rate. Optimization studies have enabled us to selectively favor the formation of the asymmetric-aminated hemi-cyanines. We next examined the role of a tertiary amine to optimize conversion to symmetrically 210 substituted truncated structures. Reacting heptamethine Cy7 with 10 equivalents of DIPEA disabled the formation of AsCy5, but improved the yield of Cy5. As listed in Table III-2, in our initial attempt, after 60 hours, we isolated 18% of Cy5. This represented a 7% improvement relative to using the secondary and tertiary amine together (entry 1). There were other compounds in this reaction, including but not limited Cy3 which were isolated and characterized, in addition to masses suggesting III-22 and III-23 species. Table III-2. Reaction optimization with tertiary amine N N I R 3N Cy5 N N solvent I temp., time Cy7 N N I Cy3 Entrya Tertiary Amine Solvent Temp. Time Product (yield %) 1 DIPEA ACN 70 °C 60 h Cy5 (18), Cy3b 2 DIPEA ACN 100 °C 30 h Cy5 (44), Cy3b 3 DIPEA ACN 180 °C 1h Cy5 (38), Cy3 (8) 4 DIPEA EtOH 70 °C 60 h Cy5b 5 DIPEA DCM 70 °C 60 h Cy5 (26), Cy3b 6 Quinuclidine ACN 70 °C 60 h Cy5 (5), Cy3 (15) 7 Quinuclidine ACN 100 °C 36 h Cy5 (10), Cy3 (21) [a] The reaction was done in sealed tube, under argon, and followed by LC-MS. [b] trace amount. 211 Increasing the temperature to 100 ºC, led to the full conversion of Cy7 in 30 hours with substantial improvement in the yield for Cy5 (44%). Increasing the temperature to 180 ºC led to complete degradation of Cy7 in 1 hour with 38% yield of Cy5. As listed in Table III-2, using 10 equivalents of DIPEA, we observed the partial formation of Cy3 in the reaction (up to 8% at 180 ºC). We also screened various solvents to observe any influence on the reaction. Switching acetonitrile to a protic solvent such as ethanol decreased the yield of Cy5 dramatically. For instance, at 70 ºC using 10 equivalents DIPEA in ethanol provided a trace amount of Cy5. While the reaction in dichloromethane had improved the yield of Cy5 to 26% (Table III-2, entry 5). Having changed the solvent and temperature, the next parameter was varying the nature of the tertiary amine. The reaction with quinuclidine finished in 36 hours at 100ºC and both Cy5 (10%) and Cy3 (21%) were observed as the products. Interestingly, the major product was to Cy3, not Cy5. To summarize the effect of tertiary amines, we saw that different tertiary amines could convert Cy7 to Cy5 (DIPEA); similarly, we can also choose to convert Cy7 to Cy3 as the favored product in the presence of quinuclidine. On the other hand, we studied the generality of this conversion by testing cyanines with different backbones (Cy7.5) in the presence of DIPEA and we observed the same pattern of the reaction with Cy5.5 being the major product (Figure III-11). 212 N N I Cy5.5 DIPEA N N ACN I 100 °C, 40 h Cy7.5 N N I Cy3.5 Figure III-11. Conversion of Cy7.5 in the presence of tertiary amine (DIPEA) The degradation pattern of di-substituted cyanine III-24 was also studied. As shown in Figure III-12, the mass of the methylated Cy5 III-25 was observed while the bromo substituted Cy5 was not observed. Compound III-25 could not be isolated as it was produced in low amounts, but as shown previously, thde asymmetric brominated Cy7 (C3′-Br-Cy7) converts to the symmetric C3′-Br-Cy5 (Figure III-7B), therefore the methyl substitution would present at C3′ position. In this reaction after 16 hours, Cy3 was the dominant signal in mass analysis. Noteworthy, there were other masses that we could not identify. 3′ N N I DIPEA III-25 N N ACN I 100 °C, 40 h Br III-24 N N I Cy3 major pdt Figure III-12. Conversion of di-substituted cyanine 213 These optimizations take advantage of the unique cyanine degradation pathways, and can easily serve as a synthetic handle to transform traditional heptamethine cyanines into a wide series of cyanines and hemi-cyanines with varying degrees of conjugation, and maximum absorption/emission that can extend the wavelength range from UV to NIR. The absorption/emission of all convertible cyanines from the blue shifted AsCy1 to the red shifted Cy7 is shown in Figure III-13. CY7 1 Abs/Em (normalized) N N I Cy7 0 600 650 700 750 800 850 Wavelength (nm) CY5 1 Abs/Em (normalized) N N I Cy5 0 500 600 700 800 Wavelength (nm) Figure III-13. Normalized absorption and emission of all cyanine’s degradation fragments 214 Figure III-13 (cont’d) CY3 1 Abs/Em (normalized) Et N N AsCy5 Et I 0 450 500 550 600 650 700 Wavelength (nm) 309 1 Abs/Em (normalized) N N I Cy3 0 450 500 550 600 650 700 Wavelength (nm) 283-DCM 1 Abs/Em (normalized) Et N N AsCy3 Et I 0 400 500 600 Wavelength (nm) 215 Figure III-13 (cont’d) Normalize of 257- DCM [Sample1] 1 Abs/Em (normalized) Et N N I AsCy1 Et 0 300 400 500 600 Wavelength (nm) III-3-3 Investigation into the mechanism of cyanine degradation The non-oxidative degradation of cyanines has not been reported and thus its mechanism would be of particular interest and significance. Initially we studied the mechanism for the conversion of Cy7 to the series of aminated hemi-cyanines. A series of studies were conducted to deduce whether Cy7 directly converts to AsCy3 and AsCy1, or alternatively, via a domino reaction, it first generates AsCy5 and subsequently AsCy5 converts to AsCy3, and further degradation leads to AsCy1. There are two main pieces of evidence in support of the former mechanistic hypothesis; 1) based on mass spectral data, AsCy5 is first formed from Cy7, and further less conjugated asymmetric Cy derivatives are generated more slowly (Figure III-10). 2) Continuation of the reaction after full conversion of Cy7, results in the yield and ratio between AsCy5, AsCy3 and AsCy1 to swing in favor of the less conjugated derivatives, pointing in the direction that AsCy5 is converting to AsCy3, which would then further convert to AsCy1. 216 To interrogate the site at which amine reacts and carbons that are lost, we resorted to deuterium labeling studies. For the synthesis of the deuterated heptamethine cyanine, a fully deuterated pyridine III-26 was converted to its Zinke Salt precursor III-27, followed by nucleophilic ring opening to yield Cy7-D5 (Figure III-14a). The deuterated cyanine was subsequently heated in the presence of diethylamine in acetonitrile as before. The asymmetric hemi-cyanine (AsCy5-D5) was isolated and identified by mass spectroetry and NMR (Figure III-14b). Retention of all five deuterium atoms is evidence for C1′- C2′ methine cleavage, following C2′ attack by the amine. In isotopic studies, the AsCy3-D3 was isolated and characterized, suggesting that the secondary amine would have attacked the C3′ methine position of AsCy5 derivative to neutralize the charge, and later, the amine’s nitrogen atom would donate its lone pair of electrons to cleave the C2′- C3′ bond. Perhaps the same steps would happen to convert the AsCy3-D3 to AsCy1-D1, since we isolated and characterized the AsCy1-D1 (Figure III-14b). 217 A. Synthesis of deuterated Cy7 OTs D NO2 D D D OTs D N III-20 N D I D D NO2 NO2 4-Bromoaniline, NaOAc D N D Toluene, 110 °C. 16 h MeOH, rt 16 h III-26 III-27 NO2 D D D N N I H D D H Cy7-D5 B. Deuterium isotopic tracing studies D D D Et N 3′ 2′ N H D D Et I AsCy5-D5 Et2NH D D D D D ACN, 70 °C Et N 2′ 1′ N N N I H D D H H D Et I Cy7-D5 AsCy3-D3 D Et N N H Et I AsCy1-D1 Figure III-14. A. Synthesis of Cy7-D5, B. Conversion of deuterated Cy7 with secondary amine 218 Deuterium isotopic labeling studies, suggest that the amine attacks the C2′ position, which upon the engagement of the nitrogen atom leads to the cleavage of the C1′- C2′. This cleavage requires a proton exchange to release the Fisher base head group. To discover the most electron dense carbon capable of the required proton exchange, we conducted a deuterium exchange study to identify the most acidic protons. Subsequently, we heated Cy7 in acetonitrile in presence of 20 equivalents of D2O and isolated and characterized (NMR and ESI-MS) the C1′-deutrated-Cy7 (III-28) as the proton exchanged cyanine product (Figure III-15A). A. D2O (20 equiv.) H H H H H H 3′ 1′ ACN, heat 3′ 1′ N 2′ N N 2′ N I I H H H H H H H D Cy7 III-28 B. H H H 3′ 1′ N 2′ N I H H H D D2O (20 equiv.) III-28 DIPEA (10 equiv.) H H H H H 3′ 1′ ACN, heat N 2′ N N I N H H H H I H H D Cy7 III-29 H H N N I H H H Cy5 Figure III-15. A. Deuterium exchange in D2O, B. Deuterium exchange in D2O and DIPEA 219 The same study performed in the presence of the 10 equivalents of DIPEA, showed the mass of the C1′-deutrated-Cy7 (III-28) and C1′-deutrated-Cy5 (III-29) in addition to Cy5 (Figure III-15B). Extended heating shows a small amount of exchange in other sites, but the C1′-exchange occurred at a faster rate. These experimental results helped us to proposed a mechanism for the conversion of Cy7 to the series of aminated hemi-cyanines (Figure III-16). Based on deuterium isotope labeling and species isolated during purification, it is likely that a secondary amine would attack the C2′ position of the methine backbone, and push the pi electrons towards the indolinium end, neutralizing the charged on the nitrogen atom (also, DFT computational modeling (EDF2/6-31G*/SM8 CH3CN) finds a free energy preference of 5.8 kcal/mol for C2′ vs C4′ attack on Cy7) (insert the computational). Following that, the proton transfer likely happens at C1′ position, according to our deuterium exchange study, to yield III-31. Subsequently, the lone pair of the amine would regenerate the conjugated cyanine by breaking the C1′- C2′ bond, yielding AsCy5 and the Fischer base III-23 (Figure III-16). AsCy5 could convert to the AsCy3 in a similar fashion. The secondary amine would attack the C3′ position (shown on the structure) of the methine backbone, and push pi electrons towards the diethyliminum end, neutralizing the charge on the nitrogen atom. Upon proton transfer, the lone pair of the amine would reestablish the conjugated cyanine that leads to formation of AsCy3. The same scenario is possible for truncation of AsCy3 to AsCy1. 220 R2NH R I R NH N 2′ N N N 1′ I Cy7 III-30 P.T. R2NH R P.T. R N R N N 3′ 1′ N N N 2′ I R III-23 III-31 H H AsCy5 I note: reversible H+ exchange at C1′ position R P.T. R I R N P.T. R NH I R R R N N N N N N R H H R AsCy3 R III-32 III-33 I Figure III-16. Proposed mechanism of cyanine conversion with secondary amines Next, we probed the mechanism for the conversion of Cy7 to symmetric Cy5. The net change in this transformation is the loss of ethyne, which from a thermodynamic perspective cannot be supported. We first subjected, a Cy7-D5 with DIPEA under the same conditions as previously employed. We successfully isolated and characterized the centrally deuterated pentamethine Cy5-D3 which presumably is derived from the cleavage of the C2′ and C3′ carbons from the backbone chain (Figure III-17). D D D DIPEA D D N N ACN, 100 °C N N I I H D D H H D H Cy5-D3 Cy7-D5 Figure III-17. Conversion of deutrated Cy7 with tertiary amine (DIPEA) 221 In our previous attempts to understand the mechanism of cyanine’s degradation in the presence of secondary amines, we observed cleavage at C1′- C2′ along with the formation of Fisher base III-23. A potential process for the conversion of Cy7 to Cy5 could be the generation of Fisher base III-23 through the aforementioned nucleophilic attack, and subsequent attack of the Fisher base to form the shortened cyanine. To support the idea of the heterocyclic indole (III-23) breaking off from the methine chain and re- attacking, we reacted a 1:1 mixture of symmetric cyanines; Cy7 and Cy7.5 with DIPEA and we were pleased to observe the mass of the scrambled heptamethine cyanine with mixed head groups, (i.e. mismatched indole cyanines), showing a clear m/z corresponding to Cy7.25 and also, recombination chain shortening which led to formation of Cy 5.25 (Figure III-18). This observation pointed us in the direction of the indole unit playing a role in displacement and re-appendage to the cyanine chain to facilitate formation of scrambled cyanines. N N I N N Cy7 DIPEA I Cy5.25 ACN, heat N N N N I I Cy7.5 Cy7.25 (Note: Mass signals for Cy5, Cy5.5, Head group and starting materials were observed as wel) Figure III-18. Recombinative chain shortening 222 Our initial hypothesis involved attack of the amine to the methine chain of the cyanine, followed by formation of a cyclobutane intermediate which would undergo the elimination of acetylene, leading to the formation of a symmetric Cy5. This proposed mechanism has two primary issues, 1) From an energetic standpoint, thermochemistry (and calculations) predict the actual loss of acetylene gas would be uphill in energy by 30-40 kcal/mol, and 2) detection and conformation of the presence of acetylene via NMR and HRMS was unsuccessful. An alternate hypothesis is supported by two facts: first of which being the observation of the indolinium head group cleavage, originating from the parent heptamethine chain between C1′- C2′ and, second, the observation of a small amount of acetaldehyde by NMR study, during the course of the reaction. In this instance, a water molecule (water was not intentionally added to the reaction directly, however a trace amount of water could have been introduced via solvent, amine or other reagents) would attack the C2′ methine carbon generating the III-34, after a proton transfer (Figure III-19). Subsequently, the lone pair of oxygen would donate its electrons, facilitating the formation of the conjugated cyanine that leads to the cleavage of the C1′- C2′ bond. This then generates aldehyde III-35, and Fischer base III-23. At this step, the Fischer base could act as a nucleophile, attacking the ß-position of the carbonyl generating Cy5 via elimination of acetaldehyde. Hydration of acetylene could effectively pay for the release of (CH)2 as its exothermicity (33 kcal/mol) compensates for what would be a high energy reaction. 223 OH2 P.T. OH N 2′ N N N I 1′ I H H III-34 Cy7 H exchange observed in D2O Base O N N N N I Cy5 O III-23 III-35 Acetaldehyde Figure III-19. Proposed mechanism of cyanine conversion with tertiary amines Lastly, we proposed a mechanism for the truncation of the heptamethine Cy7 to a symmetric trimethine Cy3. The first part of the mechanism is analogous to that described for the truncation of Cy7 to AsCy5 (Figure III-16) and Cy7 to Cy5 (Figure III-19) in which the nucleophilic attack, (amine or water) would lead to generation of Fischer’s base III- 23. With the exception of generating the free indole unit, (Fisher’s base) it could undergo an attack to a different Cy7 backbone to form III-36 (Figure III-20). Presumably of the indole attacking the C2′ carbon would generate an intermediate with three indolinium head groups (the relative m/z for this compound was observed in the reaction mass spectroscopy analysis) that upon proton transfer, converts to the observed trimethine Cy3 by donation of the nitrogen atom lone pair from one of the nearby head groups, thereby cleaving the C2′- C3′ bond (Figure III-20). Our mechanism is supported by observing the m/z of the Fisher base III-23 and the degraded fragment III-38 in the reaction mixture. 224 Base N H N I N 2′ N N I Cy7 N A N N I Cy3 P.T. N N N N B C Figure III-20. Proposed mechanism of Cy7 conversion to Cy3 In a supplementary experiment conducted to further support our mechanistic proposal, Cy7 was heated with a neutral indole containing an exocyclic methylene group (vs methyl) in acetonitrile in the absence of any amine. Interestingly, the trimethine cyanine Cy3 was observed as the main product (Figure III-21). N III-23 N N ACN, heat N N I I Cy7 Cy3 Figure III-21. Cy7 reaction with; A. neutralized head group, B. charged head group 225 In addition, to prove that a pentamethine Cy5 is not an intermediate structure facilitating conversion of Cy7 to Cy3, we subjected a pentamethine Cy5 cyanine under the same reaction conditions using tertiary amines, and did not observe formation of any trimethine cyanine in the reaction mixture (Figure III-22, Path A). To complement the prior experiment, Cy5 was heated with the neutral indole in acetonitrile in absence of the tertiary amine, and as expected, Cy3 was not observed (Figure III-22, Path B). N DIPEA or No Observable Quinuclidine No Observable Chain Shortening ACN, heat ACN, heat Chain Shortening N N Reaction B I Reaction A Cy5 Figure III-22. Cy5 conversion reactions failed in different conditions In summary, we have discovered a non-photoactivated, oxygen-free, degradative pathway for cyanine dyes that could have important ramifications for this family of molecules. During the reaction of heptamethine cyanines (Cy7) with amine, we obtained the two-carbon truncated Cy5 and AsCy5 as major products. We optimized the reaction and were able to develop a practical and novel method for conversion of heptamethine cyanine dyes to corresponding pentamethane and trimethine cyanine derivatives with high efficiency (Figure III-23). 226 N N Cy5 N N Cy3 I I Quinuclidine, DIPEA, CH3CN, 100 ºC CH3CN, 100 ºC Et2NH, CH3CN, 110 ºC R N N N N I Cy7 AsCy1 R I Et2NH, Et2NH, CH3CN, r.t. CH3CN, 70 ºC AsCy5 AsCy3 R R N N N N R I R I Figure III-23. Optimized cyanine conversion reactions This is the first known transformation that provides products in good yields and can be tailored to produce a wide novel series of cyanines and hemi-cyanines with varying degrees of conjugation, with maximum absorption/emission that can extend the wavelength range from ultraviolet to near infrared (Figure III-24). We separated and identified all degraded species and have used deuterium label tracing studies and deuterium exchange studies in addition to other supporting experiment reactions to propose a multi-step mechanisms for the degradation to different fragments. 227 As As Cy 3 Cy Cy As Cy Cy 1 3 Cy 5 5 7 1 Absorption 0 300 400 500 600 700 800 Wavelength (nm) AsCy 1 AsCy Cy 3 3 Cy Cy As 5 7 1 Cy 5 Emission 0 400 500 600 700 800 Wavelength (nm) Figure III-24. top: Normalized absorptions (in DCM), bottom: Normalized emissions (in DCM) 228 III-3-4 Future work While the factors governing cyanine degradation pathways is critical for further developments within this chromophore family, it is of equal importance to understand the mitigation of these pathways, in an effort to bolster stability when employed in various applications. As such, our group is actively seeking to design and synthesize various substituted cyanines which, based on our understanding, would potentially hinder the previously observed conversion. The basis for appropriate structural modifications, is our prior mechanistic studies where we observed nucleophilic attack at the C2′, initiating truncation. Therefore, we aim to synthesize C2′-substituted cyanines to study the stability and propensity to degrade relative to the parent Cy7 (Figure III-25A). We also showed that the exchangeable proton at C1′ is essential for expelling Fisher base III-23, from which we hypothesize there may be valuable potential for studying C1′-substituted cyanines (Figure III-25B). A. B. R R 1′ 1′ N 2′ N N 2′ N I I R R R = Me, i-Pr Figure III-25. Cyanine structures for stability study As previously mentioned, NIR cyanines have been applied widely as fluorescent probes in biological cell imaging.4, 16, 17 The discovery of non-photoactivated cyanine degradation has inspired us to further probe this conversion in a cellular environment, in the hopes of developing a novel fluorescent probe with completely distinct fluorescent 229 emissions upon degradation. To mimic the cellular environment, we are actively studying cyanine truncation in the presence of various amino acids under different conditions. 230 III-4 Experimental section III-4-1 General remarks Molecular sieves (4Å) were dried at 160 °C under 0.25 mtorr vacuum prior to use. Unless otherwise mentioned, solvents were purified as follows. CHCl3 (amylene stabilized) was purchased from Sigma Aldrich and incubated over 4Å MS for 48 h prior to use. Toluene and CH2Cl2 were dried over CaH2 whereas and Et2O were dried over sodium (dryness was monitored by colorization of benzophenone ketyl radical); they were freshly distilled prior to use. Acetonitrile (ACN) and dimethylformamide (DMF) for reactions was HPLC grade from Sigma-Aldrich. NMR spectra were obtained using a 500 MHz or 600 MHz Varian NMR spectrometer and referenced using the residual 1H peak from the deuterated solvent. Waters 2795 (Alliance HT) instrument was used for HRMS (ESI) analysis with polyethylene glycol (PEG-400-600) as a reference. UV-Vis was performed on Agilent Cary 100 series machine and PL was recorded on Fluorolog by ISA instrument. Quantum yield measurement was performed on absolute PL quantum yield spectrometer C11347 by Hamamatsu. Column chromatography was performed using Silicycle 60Å, 35-75 µm silica gel. Pre-coated 0.25 mm thick silica gel 60 F254 plates were used for analytical TLC and visualized using UV light. 231 III-4-2 General synthesis of substituted cyanines N OTs I N III-40 R R R R p-Bromoaniline N N O2N NO2 I R R NaOAc MeOH, rt, 16 h III-39 III-41 Substituted cyanines III-40 were synthesized according to the previous reported procedures35. To a solution of corresponding Zincke salt (1 equiv.) in methanol (7 mL/mmol of Zincke salt), was added the and 4-bromoaniline (1.2 equiv.). The mixture was stirred at room temperature for 30 minutes. Then, 1,2,3,3-tetramethyl-3H-indolium iodide (3 equiv.) and NaOAc (6 equiv.) were added at once, at which point the mixture was stirred at this temperature for 16 hours. Then, diethyl ether (21 mL/mmol Zincke salt) was added, and the mixture was cooled at -15 ℃ for 3 hours. The resulting solid was collected by vacuum filtration, rinsed with water (2 x 10 mL/mmol Zincke salt) followed by diethyl ether (10 mL/mmol Zincke salt). The crude solid was then purified using column chromatography (100% DCM gradually to 15% MeOH/DCM). III-4-2-1 Analytical Data N N I Cy7 1,3,3-trimethyl-2-((1E,3E,5E)-7-((E)-1,3,3-trimethylindolin-2-ylidene)hepta-1,3,5-trien-1- yl)-3H-indol-1-ium iodide 232 The title compound was prepared according to the general procedure at 1 mmol scale. Product was isolated as a green solid (455 mg, 85%). 1H NMR (500 MHz, Methanol-d4) δ 7.65 (t, J = 13.1 Hz, 2H), 7.33 (t, J = 12.4 Hz, 1H), 7.18 (dd, J = 7.5, 1.2 Hz, 2H), 7.11 (td, J = 7.7, 1.2 Hz, 2H), 7.00 – 6.91 (m, 4H), 6.27 (t, J = 12.6 Hz, 2H), 5.98 (d, J = 13.6 Hz, 2H), 3.31 (s, 6H), 1.41 (s, 12H). 13C NMR (126 MHz, Methanol-d4) δ 173.79, 157.83, 153.00, 144.41, 142.34, 129.72, 126.94, 125.98, 123.26, 111.61, 104.79, 50.24, 31.45, 27.89. N N I Br C3′-Br-Cy7 2-((1E,3Z,5E)-3-bromo-7-((E)-1,3,3-trimethylindolin-2-ylidene)hepta-1,3,5-trien-1-yl)- 1,3,3-trimethyl-3H-indol-1-ium The title compound was prepared according to the general procedure at 1 mmol scale. Product was isolated as a green solid (577 mg, 94%). 1H-NMR (500 MHz, Methanol-d4): δ 8.16 (dd, J = 14.2, 12.1 Hz, 1H), 7.95 (d, J = 13.10 Hz, 1H), 7.85 (d, J = 12.6 Hz, 1H), 7.56 (dt, J = 7.4, 1.0 Hz, 1H), 7.50-7.43 (m, 3H), 7.41- 7.34 (m, 2H), 7.27-7.20 (m, 2H), 6.85 (t, J = 12.3 Hz, 1H), 6.60 (d, J = 14.2 Hz, 1H), 6.23 (d, J = 13.0 Hz, 1H), 3.75 (s, 3H), 3.59 (s, 3H), 1.74 (s, 6H), 1.72 (s, 6H). 233 13C-NMR (126 MHz, Methanol-d4): δ 177.33, 173.28, 155.16, 153.74, 146.93, 144.46, 143.94, 143.13, 142.03, 129.96, 129.68, 127.59, 125.73, 123.47, 123.26, 116.34, 112.98, 111.34, 108.08, 101.56, 51.31, 50.06, 32.30, 31.30, 27.88, 27.54. N N I Br III-24 2-((1E,3Z,5E)-3-bromo-5-methyl-7-((E)-1,3,3-trimethylindolin-2-ylidene)hepta-1,3,5- trien-1-yl)-1,3,3-trimethyl-3H-indol-1-ium iodide The title compound was prepared according to the general procedure at 1 mmol scale. Product was isolated as a green solid (314 mg, 50%). 1H-NMR (500 MHz, DMSO-d6): δ 8.07 (d, J = 14.7 Hz, 1H), 7.97 – 7.90 (m, 2H), 7.70 (d, J = 7.4 Hz, 1H), 7.59 – 7.55 (m, 2H), 7.51 – 7.46 (tm, 1H), 7.40 – 7.33 (m, 3H), 7.22 – 7.17 (m, 1H), 6.44 (d, J = 14.7 Hz, 1H), 6.09 (d, J = 12.9 Hz, 1H), 3.79 (s, 3H), 3.55 (s, 3H), 2.38 (s, 3H), 1.71 (s, 6H), 1.65 (s, 6H). 13C NMR (126 MHz, DMSO-d6): δ 175.54, 172.04, 170.81, 156.09, 152.32, 145.95, 143.03, 142.46, 141.75, 140.45, 128.60, 128.36, 126.24, 124.08, 122.51, 122.29, 112.41, 111.07, 110.47, 103.65, 99.71, 49.79, 48.34, 32.10, 30.82, 27.15, 26.58, 13.65. 234 D D D N N I D D Cy7-D5 1,3,3-trimethyl-2-((1E,3E,5E)-7-((E)-1,3,3-trimethylindolin-2-ylidene)hepta-1,3,5-trien-1- yl-2,3,4,5,6-d5)-3H-indol-1-ium iodide The title compound was prepared according to the general procedure at 0.1 mmol scale. Product was isolated as a dark green solid (24 mg, 60%) 1H-NMR (500 MHz, Methanol-d4): δ 7.47 (d, J = 7.5 Hz, 2H), 7.42 – 7.38 (m, 2H), 7.28 – 7.22 (m, 4H), 6.26 (bs, 2H), 3.59 (s, 6H), 1.69 (s, 12H). 13C NMR (151 MHz, Methanol-d4) δ 172.34, 155.69, 151.11, 143.01, 140.95, 128.31, 125.15, 124.55, 121.87, 110.23, 103.32, 48.83, 30.25, 26.57. HRMS (ESI+): calcd. for C29H28 D5N2+ [M-I–]: 414.2952; found 414.2950 III-4-3 General Procedure for cyanine degradation III-4-3-1 General Procedure: Cyanine degradation with amine and base I N N R2NH R 3N Cy5 N N ACN, heat I Cy7 Et N N AsCy5 Et I 235 In a 15 mL sealed tube, was added dry acetonitrile (0.03 mM) and degassed under an atmosphere of argon for a period of 15 minutes. Then, the cyanine derivative (1 equiv.) was added, followed by the secondary amine (10 equiv.), base (2 equiv.) followed placing it in a pre-heated oil bath in the dark. The reaction mixture was stirred at the desired temperature for the designated time and monitored by LC-MS, before cooling to room temperature. The solvent was removed under reduced pressure, and the residue purified via column chromatography (100% DCM gradually to 10% MeOH/DCM). III-4-3-2 General Procedure: Cyanine degradation with amine only N N I Cy5 R R2NH N N ACN, heat AsCy5 R I N N I Cy7 R N N AsCy3 R I R N N I AsCy1 R In a 15 mL sealed tube, was added dry acetonitrile (0.03 mM) and degassed under an atmosphere of argon for a period of 15 minutes. Then, the cyanine derivative (1 equiv.) was added, followed by the secondary amine (10 equiv.) followed by capping the mixture prior to placing it in a pre-heated oil bath in the dark. The mixture was stirred at the desired 236 temperature for the designated time and monitored by LC-MS, before removing and cooling to room temperature. The solvent was removed under reduced pressure, and the residue directly purified via column chromatography (100% DCM gradually to 10% MeOH/DCM). III-4-3-3 General Procedure: Cyanine degradation with base only I N N R 3N Cy5 ACN, heat N N I Cy7 N N I Cy3 In a 15 mL sealed tube, was added dry acetonitrile (0.03 mM) and degassed under an atmosphere of argon for a period of 15 minutes. Then, the cyanine derivative (1 equiv.) was added, followed by the base (10 equiv.) followed by capping the mixture prior to placing it in a pre-heated oil bath in the dark. The mixture was stirred at the desired temperature for the designated time and monitored by LC-MS, before removing and cooling to room temperature. The solvent was removed under reduced pressure, and the residue directly purified via column chromatography (100% DCM gradually to 10% MeOH/DCM). 237 III-4-3-4 Analytical Data N N I Cy5 1,3,3-trimethyl-2-((1E,3E)-5-((E)-1,3,3-trimethylindolin-2-ylidene)penta-1,3-dien-1-yl)- 3H-indol-1-ium iodide The title compound was isolated according to the general procedure III-4-3-3 with DIPEA as the base at 0.05 mmol scale, 100°C and 30 h. The product was isolated as dark blue solid (11.8 mg, 44%). 1H-NMR (500 MHz, Methanol-d4): δ 8.23 (t, J = 13.1 Hz, 2H), 7.46 (d, J = 7.4 Hz, 2H), 7.37 (t, J = 7.7 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 7.22 (t, J = 7.5 Hz, 2H), 6.67 (t, J = 12.4 Hz, 1H), 6.28 (d, J = 13.7 Hz, 2H), 3.64 (s, 6H), 1.68 (s, 12H). 13C-NMR (126 MHz, Methanol-d4): δ 175.19, 155.44, 144.23, 142.52, 129.66, 126.68, 126.15, 123.27, 111.79, 104.41, 50.45, 31.71, 27.86. HRMS (ESI+): calcd. for C27H31N2+ [M-I–]: 383.2482; found 383.2477 N N I Cy7.5 238 1,1,3-trimethyl-2-((1E,3E,5E)-5-(1,1,3-trimethyl-1,3-dihydro-2H-benzo[e]indol-2- ylidene)penta-1,3-dien-1-yl)-1H-benzo[e]indol-3-ium iodide The title compound was isolated according to the general procedure III-4-3-3 with DIPEA as the base at 0.05 mmol scale, 100°C and 40 h. The product was isolated as dark blue solid (7.3 mg, 24%). 1H-NMR (500 MHz, Methanol-d4): δ 8.37 (t, J = 12.4 Hz, 2H), 8.25 (d, J = 8.6 Hz, 2H), 8.04 – 7.98 (m, 4H), 7.67 – 7.60 (m, 4H), 7.50 – 7.46 (m 2H), 6.68 (t, J = 12.4 Hz, 1H), 6.33 (d, J = 13.8 Hz, 2H), 3.76 (s, 6H), 2.02 (s, 12H). 13C-NMR (126 MHz, Methanol-d4): δ 176.44, 154.42, 141.68, 134.86, 133.40, 131.66, 131.12, 129.42, 128.72, 126.04, 123.34, 111.92, 103.99, 52.35, 31.83, 27.49. N N I Br C3′-Br-Cy5 2-((1E,3Z)-3-bromo-5-((E)-1,3,3-trimethylindolin-2-ylidene)penta-1,3-dien-1-yl)-1,3,3- trimethyl-3H-indol-1-ium iodide The title compound was isolated according to the general procedure III-4-3-3 with DIPEA as the base at 0.05 mmol scale, 70°C and 60 h. The product was isolated as a purple solid. 239 1H-NMR (500 MHz, Methanol-d4): 𝛿 (ppm) 8.54 (d, J = 14.1 Hz, 2H), 7.53 (d, J = 7.8 Hz, 2H), 7.44 – 7.36 (m, 2H) 7.31 – 7.24 (m, 4H), 5.88 (d, J = 14.1 Hz, 2H), 3.47 (s, 6H), 1.83 (s,12H). 13C-NMR (126 MHz, Methanol-d4): 𝛿 (ppm): 174.7, 152.3, 142.7, 141.1, 128.4, 125.3, 121.9, 110.8, 100.8, 49.5, 30.3, 26.2. HRMS (ESI+): calcd. for C27H30BrN2+ [M-I–]: 461.1587; found 461.1590 D D N N I D Cy5-D3 1,3,3-trimethyl-2-((1E,3E)-5-((E)-1,3,3-trimethylindolin-2-ylidene)penta-1,3-dien-1-yl- 2,3,4-d3)-3H-indol-1-ium iodide The title compound was isolated according to the general procedure III-4-3-3 with DIPEA as the base at 0.05 mmol scale, 100°C and 30 h. The product was isolated as a dark blue solid. 1H-NMR (500 MHz, Methanol-d4): 𝛿 7.49 (dd, J = 7.5, 1.2 Hz, 2H), 7.41 (td, J = 7.7, 1.2 Hz, 2H), 7.32 – 7.24 (m, 4H), 6.26 (s, 2H), 3.62, (s, 6H), 1.73 (s, 12H). 13C-NMR (126 MHz, Methanol-d4): 173.95, 144.3, 142.5, 129.7, 126.2, 123.3, 111.8, 104.1, 50.5, 31.5, 27.8. 240 HRMS (ESI+): calcd. for C27H28 D3N2+ [M-I–]: 386.2670; found 386.2679 N N I Cy3 1,3,3-trimethyl-2-((E)-3-((E)-1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)-3H-indol-1- ium iodide The title compound was isolated according to the general procedure III-4-3-3 with quinuclidine as the base at 0.05 mmol scale, 100°C and 36 h. The product was isolated as pink-red solid (5.6 mg, 21%). 1H-NMR (500 MHz, Methanol-d4): δ 8.56 (t, J = 13.5 Hz, 1H), 7.54 (dt, J = 7.3, 1.0 Hz, 2H), 7.45 (td, J = 7.4, 1,0 HZ, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.32 (td, J = 7.5, 1.0 Hz, 2H), 6.41 (d, J = 13.5 Hz, 2H), 3.68 (s, 6H), 1.78 (s, 12H). 13C-NMR (126 MHz, Methanol-d4): δ 176.66, 152.15, 144.09, 142.06, 129.96, 126.75, 123.39, 112.24, 103.65, 49.00, 31.70, 28.15. HRMS (ESI+): calcd. for C25H29N2+ [M-I–]: 357.2325; found 357.2326 Et N N AsCy5 Et I 241 2-((1E,3E,5E)-6-(diethylamino)hexa-1,3,5-trien-1-yl)-1,3,3-trimethyl-3H-indol-1-ium iodide The title compound was isolated according to the general procedure III-4-3-2 with diethylamine at 0.05 mmol scale, r.t. and 160 h. The product was isolated as pink-red solid (8.9 mg, 41%). 1H-NMR (500 MHz, Methanol-d4): δ 7.91 (t, J = 13.1 Hz, 1H), 7.83 (d, J = 11.7 Hz, 1H), 7.64 (t, J = 12.7 Hz, 1H), 7.43 – 7.39 (m, 1H), 7.37 – 7.32 (m, 1H), 7.16 – 7.14 (m, 2H), 6.48 (t, J = 12.6 Hz, 1H), 6.19 (t, J = 13.1 Hz, 1H), 6.02 (d, J = 13.1 Hz, 1H), 3.65 (q, J = 7.3 Hz, 4H), 3.48 (s, 3H), 1.65 (s, 6H), 1.36 (t, J = 7.2 Hz, 3H), 1.31 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, Methanol-d4) δ 171.23, 161.58, 161.46, 152.54, 143.20, 140.25, 131.60, 128.12, 121.97, 121.68, 109.29, 107.98, 99.80, 51.99, 44.20,29.36, 26.77, 13.11, 11.45. HRMS (ESI+): calcd. for C21H29N2+ [M-I–]: 309.2325; found 309.2327 D D D Et N N H D D Et I AsCy5-D5 N-ethyl-N-((2E,4E)-6-((E)-1,3,3-trimethylindolin-2-ylidene)hexa-2,4-dien-1-ylidene- 1,2,3,4,5-d5)ethanaminium iodide 242 The title compound was isolated according to the general procedure III-4-3-2 with diethylamine at 0.05 mmol scale, 70°C and 40 h. The product was isolated as red solid. 1H NMR (500 MHz, Methanol-d4) δ 7.42 – 7.33 (m, 2H), 7.16 (t, J = 7.5 Hz, 2H), 6.01 (s, 1H), 3.65 (q, J = 7.2 Hz, 4H), 3.48 (s, 3H), 1.65 (s, 6H), 1.34 – 1.29 (m, 6H). HRMS (ESI+): calcd. for C21H24D5N2+ [M-I–]: 314.2639; found 314.2638 N N I O M-As-Cy5 4-((2E,4E)-6-((E)-1,3,3-trimethylindolin-2-ylidene)hexa-2,4-dien-1-ylidene)morpholin-4- ium iodide The title compound was isolated according to the general procedure III-4-3-2 with morpholine at 0.05 mmol scale, r.t. and 20 h. The product was isolated as purple-red solid (9 mg, 40%). 1H NMR (500 MHz, Methanol-d4): δ 7.96 (t, J = 13.1 Hz, 1H), 7.77 (d, J = 11.7 Hz, 1H), 7.65 (t, J = 12.7 Hz, 1H), 7.45 – 7.42 (m, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.22 – 7.18 (m, 2H), 6.48 (t, J = 12.7 Hz, 1H), 6.21 (t, J = 11.7 Hz, 1H), 6.08 (d, J = 13.5 Hz, 1H), 3.85 – 3.80 (m, 4H), 3.75 – 3.72 (m, 4H), 3.52 (s, 3H), 1.66 (s, 6H). HRMS (ESI+): calcd. for C21H27N2O+ [M-I–]: 323.2118; found 323.2124 243 Et N N Br Et I As-Br-Cy5 N-((2Z,4E)-3-bromo-6-((E)-1,3,3-trimethylindolin-2-ylidene)hexa-2,4-dien-1-ylidene)-N- ethylethanaminium The title compound was isolated according to the general procedure III-4-3-2 with diethylamine at 0.05 mmol scale, 70°C and 40 h. The product was isolated as a purple solid. 1H NMR (500 MHz, Methanol-d4): δ (ppm) 8.04 (d, J = 13.1 Hz, 1H), 7.97 (d, J = 11.6 Hz, 1H), 7.82 (d, J = 12.5 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.43 – 7.39 (m, 1H), 7.29 – 7.24 (m, 2H), 6.28 (t, J = 12.1 Hz, 1H), 6.20 (d, J = 13.1 Hz, 1H), 3.72 (m, 4H), 3.60 (s, 3H), 1.68 (s, 6H), 1.39 (m, 6H). HRMS (ESI+): calcd. for C21H28BrN2+ [M-I–]: 387.1430; found 387.1438 Et N N AsCy3 Et I 2-((1E,3E)-4-(diethylamino)buta-1,3-dien-1-yl)-1,3,3-trimethyl-3H-indol-1-ium iodide 244 The title compound was isolated according to the general procedure III-4-3-2 with diethylamine at 0.05 mmol scale, 70°C and 40 h. The product was isolated as an orange solid. 1H NMR (500 MHz, Methanol-d4) δ 8.24 – 8.15 (t, J = 12.7 Hz, 1H), 8.02 (d, J = 11.7 Hz, 1H), 7.48 – 7.43 (m, 1H), 7.39 (ddd, J = 8.5, 7.5, 1.2 Hz, 1H), 7.29 – 7.16 (m, 2H), 6.24 – 6.11 (m, 2H), 3.68 – 3.61 (m, 4H), 3.54 (s, 3H), 1.68 (s, 6H), 1.40 – 1.32 (m, 6H). 13C NMR (126 MHz, Methanol-d4) δ 175.72, 162.97, 159.11, 130.87, 129.65, 125.75, 123.19, 117.18, 111.34, 108.26, 100.51, 53.24, 45.43, 30.78, 28.08, 14.55, 12.80. HRMS (ESI+): calcd. for C19H27N2+ [M-I–]: 283.2174; found 283.2179 D D Et N N D Et I AsCy3 N-ethyl-N-((E)-4-((E)-1,3,3-trimethylindolin-2-ylidene)but-2-en-1-ylidene-1,2,3- d3)ethanaminium iodide The title compound was isolated according to the general procedure III-4-3-2 with diethylamine at 0.05 mmol scale, 70°C and 40 h. The product was isolated as an orange solid. 245 1H NMR (500 MHz, Methanol-d4) δ 7.45 (d, J = 7.4 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.25 – 7.21 (m, 2H), 6.15 (s, 1H), 3.64 (q, J = 7.3 Hz, 4H), 3.54 (s, 3H), 1.68 (s, 6H), 1.37 (t, J = 7.3 Hz, 3H), 1.33 (t, J = 7.3 Hz, 3H). 13C NMR (201 MHz, Methanol-d4) δ174.24, 172.03, 161.67 (t, J = 31.4 Hz), 161.14 (t, J = 24.9 Hz), 157.24 (t, J = 22.8 Hz), 129.47, 128.24, 124.31, 121.79, 109.92, 98.92, 51.76, 43.96, 31.69, 26.67, 13.15, 11.39. HRMS (ESI+): calcd. for C19H24 D3N2+ [M-I–]: 286.2357; found 286.2353 Et N N I AsCy1 Et (E)-2-(2-(diethylamino)vinyl)-1,3,3-trimethyl-3H-indol-1-ium iodide The title compound was isolated according to the general procedure III-4-3-2 with diethylamine at 0.05 mmol scale, 110°C and 30 h. The product was isolated as a yellow solid. 1H-NMR (500 MHz, Methanol-d4): δ 8.27 (d, J = 12.8 Hz, 1H), 7.50 (d, J = 7.4, 1H), 7.43 (td, J = 7.7, 1.2 Hz, 1H), 7.34 – 7.27 (m, 2H), 5.67 (d, J = 12.9 Hz, 1H), 3.80 – 3.70 (m, 4H), 3.62 (s, 3H), 1.68 (s, 6H), 1.41-1.35 (m, 6H). HRMS (ESI+): calcd. for C17H25N2+ [M-I–]: 257.2018; found 257.2126 246 N N I O M-As-Cy3 4-((E)-4-((E)-1,3,3-trimethylindolin-2-ylidene)but-2-en-1-ylidene)morpholin-4-ium iodide The title compound was isolated according to the general procedure III-4-3-2 with morpholine at 0.05 mmol scale, 70°C and 24 h. The product was isolated as an orange solid. 1H-NMR (500 MHz, Methanol-d4): δ 8.21 (t, J = 12.9 Hz, 1H), 7.98 (d, J = 11.7 Hz, 1H), 7.47 (d, J = 7.4 Hz, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.28-7.23 (m, 2H), 6.24 (t, J = 12.7 Hz, 1H), 6.18 (d, J = 13.7 Hz, 1H), 3.86 – 3.81 (m, 4H), 3.76 – 3.71 (m, 4H), 3.57, (s, 3H), 1.68 (s, 6H). 13C NMR (126 MHz, Methanol-d4): δ 176.27, 162.49, 159.48, 144.15, 142.01, 129.69, 126.03, 123.24, 111.61, 107.27, 101.04, 68.08, 67.11, 56.17, 30.77, 28.04. HRMS (ESI+): calcd. for C19H25N2O+ [M-I–]: 297.1961; found 297.1976 III-4-4 General Procedure for synthesis of Zincke salts R OTs R N NO2 OTs N NO2 Toluene, 110 °C, 16 h NO2 NO2 III-20 III-39 247 Substituted Zincke salts III-39 were synthesized according to the previous reported procedures.35 To a mixture 2,4-dinitrophenyl p-toluenesulfonate III-20 (1.1 equiv.) in toluene (7 mL/mmol) was added the corresponding pyridine derivative (1 equiv.) The reaction mixture was refluxed for 16 h and then cooled to rt. Vacuum filtration was used to isolate the suspended solids, which were then washed with toluene (2 × 5 mL/mmol) and Et2O (2×5 mL/mmol), and dried under vacuum to give the Zincke salt products. III-4-4-1 Analytical Data N OTs NO2 NO2 III-42 1-(2,4-dinitrophenyl)pyridin-1-ium 4-methylbenzenesulfonate The title compound was isolated according to the general procedure at 3 mmol scale,. The product was isolated as a white solid (1 g, 80%). 1H-NMR (500 MHz, DMSO-d6): δ (ppm) 9.42-9.35 (m, 2H), 9.12 (d, J = 2.5 Hz, 1H), 9.00-9.81 (m, 2H), 8.48-8.37 (m, 3H), 7.46 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 2.28 (s, 3H). 13C NMR (126 MHz, DMSO-d6): δ (ppm) 149.1, 148.8, 146.1, 145.8, 143.0, 138.7, 137.5, 131.9, 130.2, 128.0, 125.5, 121.4, 20.8. 248 D D D OTs D N D NO2 NO2 III-27 1-(2,4-dinitrophenyl)pyridin-1-ium-2,3,4,5,6-d5 4-methylbenzenesulfonate The title compound was isolated according to the general procedure at 3 mmol scale,. The product was isolated as a white solid (760 mg, 60%). 1H-NMR (500 MHz, DMSO-d6): δ (ppm) 9.12 (d, J = 2.4 Hz, 1H), 8.97 (dd, J = 8.7, 2.4 Hz, 1H) 8.42 (d, J = 8.7 Hz, 1H), 7.45 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 7.5 Hz, 2H), 2.28 (s, 3H). 13C NMR (126 MHz, DMSO-d6): 149.18, 145.84, 144.64, 143.08, 138.68, 137.54, 136.36, 131.88, 130.23, 128.05, 125.50, 121.46, 20.80. HRMS (ESI+): calcd. for C11H3 D5N3O4 [M-TsO–]: 251.0823; found 251.0850 Br N OTs NO2 NO2 III-43 3-bromo-1-(2,4-dinitrophenyl)pyridin-1-ium 4-methylbenzenesulfonate 249 The title compound was isolated according to the general procedure at 3 mmol scale,. The product was isolated as a white solid (1.38 g, 93%). 1H-NMR (500 MHz, DMSO-d6): δ (ppm) 9.85 (d, J = 1.7 Hz, 1H), 9.44 (dt, J = 6.1, 1.2 Hz, 1H), 9.30-9.19 (m, 1H), 9.10 (d, J = 2.5 Hz, 1H), 8.97 (dd, J = 8.7, 2.5 Hz, 1H), 8.43 – 8.37 (m, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 2.28 (3H). 13C NMR (126 MHz, DMSO-d6): δ 151.10, 149.26, 147.27, 145.71, 145.35, 142.80, 137.98, 137.61, 132.03, 130.24, 128.65, 128.06, 125.47, 121.84, 121.36, 20.80. Me Br N OTs NO2 NO2 III-44 3-bromo-1-(2,4-dinitrophenyl)-5-methylpyridin-1-ium 4-methylbenzenesulfonate The title compound was isolated according to the general procedure at 1 mmol scale,. The product was isolated as a white solid (270 mg, 53%). 1H-NMR (500 MHz, DMSO-d6): δ (ppm) 9.70 – 9.67 (m, 1H), 9.36 – 9.34 (m, 1H), 9.16 – 9.13 (m, 1H), 9.12 (d, J = 2.4 Hz, 1H), 8.99 (dd, J = 8.7, 2.6 Hz, 1H), 8.37 (d, J = 8.7 Hz, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.11 (m, 2H), 2.59 (s, 3H), 2.28 (s, 3H). 13C NMR (126 MHz, DMSO-d6): δ (ppm) 151.2, 149.3, 145.8, 144.8, 144.3, 142.7, 139.8, 137.9, 137.6, 131.9, 130.3, 128.0, 125.4, 121.4, 120.9, 20.8, 17.7. 250 REFERENCES (1) Lou, Z. R.; Li, P.; Song, P.; Han, K. L. Ratiometric fluorescence imaging of cellular hypochlorous acid based on heptamethine cyanine dyes. Analyst 2013, 138 (21), 6291-6295. DOI: 10.1039/c3an00198a. (2) Geiger, T.; Schoger, I.; Rentsch, D.; Veron, A. C.; Oswald, F.; Meyer, T.; Nuesch, F. Unsymmetrical Heptamethine Dyes for NIR Dye-Sensitized Solar Cells. Int J Photoenergy 2014, 2014. DOI: Artn 25898410.1155/2014/258984. (3) Ooyama, Y.; Harima, Y. Photophysical and Electrochemical Properties, and Molecular Structures of Organic Dyes for Dye-Sensitized Solar Cells. Chemphyschem 2012, 13 (18), 4032-4080. DOI: 10.1002/cphc.201200218. (4) Shi, C. H.; Wu, J. B.; Pan, D. F. Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy. J Biomed Opt 2016, 21 (5). DOI: Artn 05090110.1117/1.Jbo.21.5.050901. (5) Sun, W.; Guo, S. G.; Hu, C.; Fan, J. L.; Peng, X. J. Recent Development of Chemosensors Based on Cyanine Platforms. Chem Rev 2016, 116 (14), 7768- 7817. DOI: 10.1021/acs.chemrev.6b00001. (6) Hong, G. S.; Antaris, A. L.; Dai, H. J. Near-infrared fluorophores for biomedical imaging. Nat Biomed Eng 2017, 1 (1). DOI: ARTN 001010.1038/s41551-016-0010. (7) Traverse, C. J.; Pandey, R.; Barr, M. C.; Lunt, R. R. Emergence of highly transparent photovoltaics for distributed applications. Nat Energy 2017, 2 (11). DOI: 10.1038/s41560-017-0016-9. (8) Kiyose, K.; Aizawa, S.; Sasaki, E.; Kojima, H.; Hanaoka, K.; Terai, T.; Urano, Y.; Nagano, T. Molecular Design Strategies for Near-Infrared Ratiometric Fluorescent Probes Based on the Unique Spectral Properties of Aminocyanines. Chem-Eur J 2009, 15 (36), 9191-9200. DOI: 10.1002/chem.200900035. (9) Samanta, A.; Vendrell, M.; Das, R.; Chang, Y. T. Development of photostable near- infrared cyanine dyes. Chem Commun 2010, 46 (39), 7406-7408. DOI: 10.1039/c0cc02366c. (10) Arjona-Esteban, A.; Stolte, M.; Wurthner, F. Conformational Switching of pi- Conjugated Junctions from Merocyanine to Cyanine States by Solvent Polarity. Angew Chem Int Edit 2016, 55 (7), 2470-2473. DOI: 10.1002/anie.201510620. (11) Davydenko, I.; Barlow, S.; Sharma, R.; Benis, S.; Simon, J.; Allen, T. G.; Cooper, M. W.; Khrustalev, V.; Jucov, E. V.; Castaneda, R.; et al. Facile Incorporation of Pd(PPh3)(2)Hal Substituents into Polymethines, Merocyanines, and Perylene 251 Diimides as a Means of Suppressing Intermolecular Interactions. J Am Chem Soc 2016, 138 (32), 10112-10115. DOI: 10.1021/jacs.6b06361. (12) Gopika, G. S.; Prasad, P. M. H.; Lekshmi, A. G.; Lekshmypriya, S.; Sreesaila, S.; Arunima, C.; Kumar, M. S.; Anil, A.; Sreekumar, A.; Pillai, Z. S. Chemistry of cyanine dyes-A review. Mater Today-Proc 2021, 46, 3102-3108. DOI: 10.1016/j.matpr.2021.02.622. (13) Bilici, K.; Cetin, S.; Aydindogan, E.; Acar, H. Y.; Kolemen, S. Recent Advances in Cyanine-Based Phototherapy Agents. Front Chem 2021, 9. DOI: ARTN 70787610.3389/fchem.2021.707876. (14) Usama, S. M.; Thavornpradit, S.; Burgess, K. Optimized Heptamethine Cyanines for Photodynamic Therapy. Acs Appl Bio Mater 2018, 1 (4), 1195-1205. DOI: 10.1021/acsabm.8b00414. (15) Lange, N.; Szlasa, W.; Saczko, J.; Chwilkowska, A. Potential of Cyanine Derived Dyes in Photodynamic Therapy. Pharmaceutics 2021, 13 (6). DOI: ARTN 81810.3390/pharmaceutics13060818. (16) Li, Y.; Zhou, Y. M.; Yue, X. L.; Dai, Z. F. Cyanine Conjugate-Based Biomedical Imaging Probes. Adv Healthc Mater 2020, 9 (22). DOI: ARTN 200132710.1002/adhm.202001327. (17) Onoe, S.; Temma, T.; Shimizu, Y.; Ono, M.; Saji, H. Investigation of cyanine dyes for in vivo optical imaging of altered mitochondrial membrane potential in tumors. Cancer Med-Us 2014, 3 (4), 775-786. DOI: 10.1002/cam4.252. (18) Malinkiewicz, O.; Grancha, T.; Molina-Ontoria, A.; Soriano, A.; Brine, H.; Bolink, H. J. Efficient, Cyanine Dye Based Bilayer Solar Cells. Adv Energy Mater 2013, 3 (4), 472-477. DOI: 10.1002/aenm.201200764. (19) Yang, C. C.; Liu, D. Y.; Rennya, A.; Kuttipillai, P. S.; Lunt, R. R. Integration of near- infrared harvesting transparent luminescent solar concentrators onto arbitrary surfaces. J Lumin 2019, 210, 239-246. DOI: 10.1016/j.jlumin.2019.02.042. (20) Zhao, Y. M.; Meek, G. A.; Levine, B. G.; Lunt, R. R. Near-Infrared Harvesting Transparent Luminescent Solar Concentrators. Adv Opt Mater 2014, 2 (7), 606- 611. DOI: 10.1002/adom.201400103. (21) Yang, C. C.; Zhang, J.; Peng, W. T.; Sheng, W.; Liu, D. Y.; Kuttipillai, P. S.; Young, M.; Donahue, M. R.; Levine, B. G.; Borhan, B.; et al. Impact of Stokes Shift on the Performance of Near-Infrared Harvesting Transparent Luminescent Solar Concentrators. Sci Rep-Uk 2018, 8. DOI: ARTN 1635910.1038/s41598-018- 34442-3. 252 (22) Byers, G. W.; Gross, S.; Henrichs, P. M. Direct and Sensitized Photooxidation of Cyanine Dyes. Photochem Photobiol 1976, 23 (1), 37-43. DOI: DOI 10.1111/j.1751-1097.1976.tb06768.x. (23) Patel, N. J.; Manivannan, E.; Joshi, P.; Ohulchanskyy, T. J.; Nani, R. R.; Schnermann, M. J.; Pandey, R. K. Impact of Substituents in Tumor Uptake and Fluorescence Imaging Ability of Near-Infrared Cyanine-like Dyes. Photochem Photobiol 2015, 91 (5), 1219-1230. DOI: 10.1111/php.12482. (24) Toutchkine, A.; Nguyen, D. V.; Hahn, K. M. Merocyanine dyes with improved photostability. Org Lett 2007, 9 (15), 2775-2777. DOI: 10.1021/ol070780h. (25) Nani, R. R.; Kelley, J. A.; Ivanic, J.; Schnermann, M. J. Reactive species involved in the regioselective photooxidation of heptamethine cyanines. Chem Sci 2015, 6 (11), 6556-6563. DOI: 10.1039/c5sc02396c. (26) Gorka, A. P.; Nani, R. R.; Zhu, J. J.; Mackem, S.; Schnermann, M. J. A Near-IR Uncaging Strategy Based on Cyanine Photochemistry. J Am Chem Soc 2014, 136 (40), 14153-14159. DOI: 10.1021/ja5065203. (27) Oushiki, D.; Kojima, H.; Terai, T.; Arita, M.; Hanaoka, K.; Urano, Y.; Nagano, T. Development and Application of a Near-Infrared Fluorescence Probe for Oxidative Stress Based on Differential Reactivity of Linked Cyanine Dyes. J Am Chem Soc 2010, 132 (8), 2795-2801. DOI: 10.1021/ja910090v. (28) Sun, M. T.; Yu, H.; Zhu, H. J.; Ma, F.; Zhang, S.; Huang, D. J.; Wang, S. H. Oxidative Cleavage-Based Near-Infrared Fluorescent Probe for Hypochlorous Acid Detection and Myeloperoxidase Activity Evaluation. Anal Chem 2014, 86 (1), 671-677. DOI: 10.1021/ac403603r. (29) Dirix, L.; Kennes, K.; Fron, E.; Debyser, Z.; van der Auweraer, M.; Hofkens, J.; Rocha, S. Photoconversion of Far-Red Organic Dyes: Implications for Multicolor Super-Resolution Imaging. Chemphotochem 2018, 2 (5), 433-441. DOI: 10.1002/cptc.201700216. (30) Stone, M. B.; Veatch, S. L. Far-Red Organic Fluorophores Contain a Fluorescent Impurity. Chemphyschem 2014, 15 (11), 2240-2246. DOI: 10.1002/cphc.201402002. (31) Helmerich, D. A.; Beliu, G.; Matikonda, S. S.; Schnermann, M. J.; Sauer, M. Photoblueing of organic dyes can cause artifacts in super-resolution microscopy. Nat Methods 2021, 18 (3), 253-+. DOI: 10.1038/s41592-021-01061-2. (32) Matikonda, S. S.; Helmerich, D. A.; Meub, M.; Beliu, G.; Kollmannsberger, P.; Greer, A.; Sauer, M.; Schnermann, M. J. Defining the Basis of Cyanine Phototruncation Enables a New Approach to Single-Molecule Localization 253 Microscopy. Acs Central Sci 2021, 7 (7), 1144-1155. DOI: 10.1021/acscentsci.1c00483. (33) Cho, Y.; An, H. J.; Kim, T.; Lee, C.; Lee, N. K. Mechanism of Cyanine5 to Cyanine3 Photoconversion and Its Application for High-Density Single-Particle Tracking in a Living Cell. J Am Chem Soc 2021, 143 (35), 14125-14135. DOI: 10.1021/jacs.1c04178. (34) Zhang, J.; Moemeni, M.; Yang, C. C.; Liang, F. C.; Peng, W. T.; Levine, B. G.; Lunt, R. R.; Borhan, B. General strategy for tuning the Stokes shifts of near infrared cyanine dyes. J Mater Chem C 2020, 8 (47), 16769-16773. DOI: 10.1039/d0tc03615c. (35) Stackova, L.; Stacko, P.; Klan, P. Approach to a Substituted Heptamethine Cyanine Chain by the Ring Opening of Zincke Salts. J Am Chem Soc 2019, 141 (17), 7155-7162. DOI: 10.1021/jacs.9b02537. 254