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This is to certify that the

dissertation entitled

Synthesis of Biomimetic Model Compounds for

Studies of Proton Coupled Electron Transfer

presented by

Yongqi Deng

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SYNTHESIS OF BIOMIMETIC MODEL COMPOUNDS FOR
STUDIES OF PROTON COUPLED ELECTRON TRANSFER

By

Yongqi Deng

A DISSERTATION
Submitted to
Michigan State University

in partial fulfillment of the requirements
for the degree of

DOCTOR OF PHILOSOPHY
Department of Chemistry

1997

ABSTRACT

SYNTHESIS OF BIOMIMETIC MODEL COMPOUNDS FOR
STUDIES OF PROTON COUPLED ELECTRON TRANSFER

Yongqi Deng

Proton coupled electron transfer (PCET) is a basic energy conversion process in
biology. To elucidate the mechanism of PCET reactions, we have studied photoinduced
electron transfer between donor/acceptor pairs juxtaposed by a proton interface formed
by an amidinium-carboxylate salt bridge. This proton interface, unlike a carboxylic acid
dimer, is asymmetric and allows us to control the direction of proton transfer. Porphyrin
amidinium and porphyrin phenyl amidinium have been synthesized via their nitrile
precursors using ClAl(NH2)CH3. The corresponding porphyrin carboxylate and
porphyrin phenylcarboxylate complexes have been synthesized from aldehyde and ester
precursors, respectively. The solubility of these molecules in organic solvents has been
improved by introducing trimethoxyphenyl groups. Their capabilities to form
amidinium-carboxylate salt bridges have been characterized by X-ray crystallography,
NMR and UV-vis spectroscopies. These studies reveal that the amidinium-carboxylate
salt bridge is very stable and even persists in polar solvent such as DMSO. When the
amidinium group is directly attached to the porphyrin ring, deprotonation of the
amidinium causes a spectral shifi, indicating a strongly coupled system. However, in
porphyrin phenyl amidinium, the coupling is interrupted by the introduction of a phenyl

group.

In an effort to further investigate the proton coupling effect on ET rates, purpurin
and chlorin molecules attached with amidinium or carboxylate groups have also been
synthesized. They exhibit characteristics similar to their porphyrin analogues in the
formation of the amidinium-carboxylate salt bridge. A double bond connecting
chromophore and amidinium (carboxylate) groups in purpurin provides a strong coupling
to the interface, as indicated by UV-vis studies. In chlorin amidinium and carboxylate
complexes, this double bond is replaced by a single bond to create a decoupled system.
Unlike the porphyrin system, the length and structure of the salt bridge connector for
purpurin and chlorin complexes are the same, thus allowing for a better comparison
between these two systems.

Preliminary ET studies reveal that the ET is perturbed by the proton interface
when it is electronically coupled to the donor/acceptor chromophore. This is rationalized
by an increase in the reorganization energy when the proton is transferred.

Finally, we have designed and synthesized a novel porphyrin-quinone complex.
This complex, in which the porphyrin is substituted with pyridinium groups, is water-
soluble and allows for the study of PCET in aqueous solutions. Proton coupling is

observed to slow the back ET reaction by over four orders of magnitude.

ACKNOWLEDGEMENTS

I would like to express my special gratitude to my advisors Professor C. K. Chang
and Professor D. G. Nocera for their guidance, advice and encouragement through the
course of this work.

I wish to thank the past and present members of Professor Chang and Professor

Nocera group — Mr. Craig Shiner, Mr. Chen-Yu Yeh, Dr. Ying Liang, Mr. Baomin

Guo, Dr. J. P. Kirby, Dr. James Roberts, Mr. Dan. Engebretson, Dr. A]. Barney, Dr. Sara
Helvoigt, Mr. Dimitrisa Papoutsakis, Dr. Eric Saari, Dr. Wanda Hartmann and Dr. Ann
Macintosh for their help and friendship. I also wish to thank Mr. Mike Waldo for his
help on American culture and friendship.

Thanks are also extended to Professor Shih-Ming Peng at the Department of
Chemistry, National Taiwan University, who carry out the X-ray structure determination
of porphyrin amidinium-carboxylate complex.

My deepest appreciation is due to my wife Li Zhen for her love and support. We

are looking forward a new life together with our lovely daughter Sherry Deng.

iv

TABLE OF CONTENTS

 

 

 

 

 

 

TABLE OF CONTENTS v
LIST OF FIGURES ..... viii
LIST OF TABLES x
LIST OF APPENDIX FIGURES xi
ABBREVIATIONS xii
CHAPTER I
INTRODUCTION A - -_ -- l
I. SIGNIFICANCE AND BACKGROUND ........................................................................... l
A. PCET in photosystem II ............................................................................. 2
B. PCET in cytochrome c oxidase .................................................................. 4
II. STRATEGIES FOR PCET DESIGN ............................................................................. 7
A. Overall design ............................................................................................ 7
B. Donor-Acceptors ........................................................................................ 8
C. Porphyrin model compounds for ET studies ............................................ 10
D. Proton interfaces ...................................................................................... 14
III. RESULTS AND PRESENTATION ............................................................................. 18
CHAPTER II

SYNTHESIS OF PORPHYRINS MODIFIED WITH AMIDINIUM AND

CARBOXYLIC ACID GROUPS - 19

 

I. INTRODUCTION ...................................................................................................... 19
II. SYNTHESIS ........................................................................................................... 22

A. Porphyrin phenyl amidinium and carboxylic acid—decoupled systems. 22

B. Porphyrin amidinium and carboxylic acid—coupling system ................. 31

III. PROPERTIES .......................................................................................................... 40

A. Coupling effects ....................................................................................... 40

B. IR studies .................................................................................................. 43

IV. EXPERIMENTAL ................................................................................................... 45
CHAPTER III

CHARACTERIZATION OF AMIDINIUM-CARBOXYLATE SALT BRIDGE 74

I. CRYSTAL STRUCTURE ............................................................................................ 74
II. DETERMINATION OF ASSOCIATION CONSTANTS ................................................... 84
A. Proton NMR ............................................................................................. 84
B. UV-vis ...................................................................................................... 87
III. PCET STUDIES ................................................................................................... 96
IV. CONCLUSIONS ..................................................................................................... 98
V. EXPERIMENTAL .................................................................................................. 101
A. Crystallography ...................................................................................... 101
B. Binding studies ....................................................................................... 101
CHAPTER IV

PURPURIN AND CHLORIN — SYNTHESIS AND ELECTRON TRAN SFER.. 103

I. INTRODUCTION .................................................................................................... 103
11. RESULTS AND DISCUSSION ................................................................................. 105
A. Synthesis ................................................................................................ 105
B. Coupling vs. Decoupling ........................................................................ 109
C. Binding Studies ...................................................................................... 111
D. PCET Studies ......................................................................................... 114

vi

III. EXPERIMENTAL ................................................................................................ 126

CHAPTER V

SYNTHESIS OF WATER SOLUBLE PORPHYRIN-QUINONE

I. INTRODUCTION ....................................................................................................
II. RESULTS AND DISCUSSION .................................................................................
A. Synthesis .................................................................................................
B. Preliminary ET studies ...........................................................................

III. EXPERIMENTAL .................................................................................................

REFERENCES - .....

 

 

APPENDIX

SELECTED PROTON NMR SPECTRA-

 

vii

136

136
138
138
142
145

- 149

- 158

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

LIST OF FIGURES

PCET in Photosystem II (PSII) ......................................................................... 3
Electron transfer pathways and rates in cytochrom c oxidase ........................... 5
PCET design ...................................................................................................... 9
Secondary electrostatic interactions in amidinium-carboxylate salt bridge 15

Absorption Spectral changes of 75 upon addition of DBU in CHzCl2 (The

amount of DBU increase with arrows) ........................................................... 41
Absorption Spectral of 53 in the absent (—) and the presence of 3.00 eq. 'DBU

( ------- ) in CH2C12 .............................................................................................. 42
IR spectra of 75. (a) protonation form; (b) deprotonation form ...................... 44

Top and Side views of the ORTEP diagrams of the crystal structure of the salt-
bridged supramolecular assembly formed by association of 75 with benzoate
(structure 1) ..................................................................................................... 76
Top and Side views of the ORTEP diagrams of the crystal structure of the salt-
bridged supramolecular assembly formed by association of 75 with benzoate

(structure 2) ..................................................................................................... 77

Figure 10. Selected 1H NMR spectra of 75 (2.06 mM) with 1 eq. of benzoic acid in the

absence of and in the presence of 1.78, 3.56, 5.35, 7.13, 8.92, 10.70, and 12.48
mM (bottom to top) of tetrabutylammonium benzoate in DMSO-d6 at room

temperature. The spectral range captures the amidinium protons internal
(NHin) and external (N Hex) to the salt bridge interface and the three mesa

protons of the porphyrin ring. ......................................................................... 88

Figure 11. Plot of the chemical Shift of internal protons of the amidinium versus the

concentration of tetrabutylammonium benzoate ............................................. 89

Figure 12. Job plot of the supramolecular complex formed by 75 and benzoate. The

viii

total concentration was kept at 3.5 mM and the systems were monitored by 1H
NMR (using the internal proton of amidinium) in DMSO at room temperature.
......................................................................................................................... 90
Figure 13. Selected UV-vis spectra of 75 (5.50 uM) in the presence of 0.0, 1.36, 2.71,
4.07, 5.42, 6.78 and 9.48 uM (increase with arrows) of tetrabutylammonium
benzoate in dichloromethane. ......................................................................... 92

Figure 14. Plot of the absorption change of 75 at 398 nm versus the concentration of

tetrabutylammonium benzoate ........................................................................ 93
Figure 15. Summary of ET rates in coupling system ..................................................... 99
Figure 16. Summary of ET rates in decoupling systems .............................................. 100

Figure 17. Absorption spectra of purpurin 92 (0.81 uM) in the presence of 0.00, 0.20,
0.40, 0.60, 0.80, 1.00, 1.40, 1.80, 2.40 eq. of DBU in CHzClz. The arrows
represent the increasing of DBU. .................................................................. 112

Figure 18. Absorption spectra of chlorin 96 (0.93 uM) in the absent (—) and present of

3.00 ( ------- ) eq. of DBU in CH2C12 ................................................................. 113
Figure 19. Selected 1H NMR spectra of 96 (3.86 mM) with 1 eq. of benzoic acid in the

absence of and in the presence of 1.00, 1.69, 2.38, 3.08, 5.16, 7.23, and 10.00

mM (bottom to top) of tetrabutylammonium benzoate in DMSO-d,5 at room

temperature. The Spectral range captures the amidinium protons internal
(N Hin) and external (NHex) to the salt bridge interface and the three meso

protons of the purpurin as well as olefmic proton of the cyclopentenyl ring.
....................................................................................................................... 115
Figure 20. Plot of the chemical shift of internal protons of the amidinium versus the
concentration of tetrabutylamonium benzoate .............................................. 116
Figure 21. Selected UV-vis spectra of 92 (2.74 uM) in the presence of 0.0, 0.63, 1.26,
1.88, 2.51, 3.14, 4.40, 5.65 and 7.54 uM (increase with arrows) of
tetrabutylammonium benzoate in dichloromethane. ..................................... 1 17

Figure 22. Plot of the absorption change of 92 at 420 nm versus the concentration of

tetrabutylammonium benzoate ...................................................................... 1 18
Figure 23. Summary of ET rates in purpurin and chlorin systems ............................... 122
Figure 24. pH-dependence of forward ET (0) and back ET rates (0) ......................... 144

ix

LIST OF TABLES

Table 1. Crystal Data and Conditions for Crystallographic Data Collection and Structure
Refinement ......................................................................................................... 78

Table 2. Selected Bond Distances and Bond Angles and Their Estimated Standard

Deviations for Porphyrin Amidinium Benzoate ............................................. 79
Table 3. Atomic Parameters x,y,z and Beq. .................................................................... 80
Table 4. Association Constants (K,) and Energies (AG°) of Amidinium-Carboxylate Salt
Bridge in DMSO Determined by NMR Titration ........................................... 91
Table 5. Association Constants (K) and Energies (AG°) of Complexes Formed by 75 and
Various Carboxylates ...................................................................................... 95
Table 6. Association Constants (K,) of Amidinium-Carboxylate Salt bridge for Purpurin
and Chlorin Systems ..................................................................................... 119

Table 7. Distances, Driving Forces and ET Rate Constants for Purpurin and Chlorin
Systems ......................................................................................................... 123

Figure A-l.
Figure A-2.
Figure A-3.
Figure A-4.
Figure A-5.
Figure A-6.
Figure A-7.
Figure A-8.
Figure A-9.
' Figure A—10.
Figure A-l 1.
Figure A-12.
Figure A-13.
Figure A-l4.
Figure A-15.
Figure A-16.
Figure A-17.
Figure A-18.
Figure A-19.
Figure A-20.

LIST OF APPENDIX FIGURES

300 MHz 1H-NMR spectrum of 48 in CDCl3 ................................................. 158
300 MHz 1H-NMR spectrum of 51 in CDC13 ................................................. 159
300 MHz 1H-NMR spectrum of 53 in CDCI3 ................................................. 160
300 MHz 1H-NMR spectrum of 66 in CDCl3 ................................................. 161
300 MHz 1H-NMR spectrum of 67 in CDCl3 ................................................. 162
300 MHz 1H-NMR spectrum of 68 in CDC]; ................................................. 163
300 MHz 1H-NMR spectrum of 69 in CDCI3 ................................................. 164
300 MHz 1H-NMR spectrum of 70 in CDCl3 ................................................. 165
300 MHz 1H-NMR spectrum of 71 in CDC13 ................................................. 166
300 MHz 1H-NMR spectrum of 73 in CDCl3 ............................................... 167
300 MHz 1H-NMR spectrum of 75 in CDCI3 ............................................... 168
300 MHz 1H-NMR Spectrum of 83 in CDCl3 ............................................... 169
300 MHz ‘H-NMR spectrum of 85 m CDC13 ............................................... 170
300 MHz 1H-NMR spectrum of 89 in CDCI3 ............................................... 171
300 MHz 1H-NMR spectrum of 90 in CDC13 ............................................... 172
300 MHz 1H-NMR spectrum of 92 in CDC13 ............................................... 173
300 MHz 1H-NMR spectrum of 96 in CDC]; ............................................... 174
300 MHz 1H-NMR spectrum of 105 in DMSO ............................................ 175
300 MHz 1H-NMR spectrum of 106 in D20 ................................................. 176
300 MHz 1H-NMR spectrum of 108 in D20 ................................................. 177

xi

DBU

DMF

DMSO

DNB

DNBA

FAB-MS

FT—IR

OEP

PDC

TABA

TFA

TLC

TTP

ABBREVIATIONS

1 ,8-Diazabicyclo[5,4,0] undec-7-ene
N,N-Dirnethyl F ormamide

Dimethyl Sulfoxide
3,5-Dinitrobenzoate
3,5-Dinitrobenzamidinium

Fast Atom Bombardment Mass Spectroscopy
Fourier Transformed Infra Red
2,3,7,8,12,13,17,18-Octaethylporphyrin
Pyridiniurn Dichromate
Tetrabutylammonium Benzoate
Tetrahydrafuran

Trifluoroacetic Acid

Thin Layer Chromatography

5 ,1 0,1 5,20-Tetraphenylporphyrin

xii

Chapter I

Introduction

I. Significance and Background

Proton coupled electron transfer (PCET) is a basic energy conversion process in
biology. The importance of PCET was realized during the 19605 when many biochemists
were unsuccessfully searching for a high energy phosphorylated intermediate in the
synthesis of adenosine triphosphate (ATP), which is the universal energy storage form in
living cells. In 1961, Peter Mithchelll suggested such intermediate did not exist. Instead,
he proposed a chemiosmotic theory for oxidative and photosynthetic phosphorylation.
According to his concept, the key intermediate is an electrochemical gradient across the
inner mitochondrial or thylakoid membrane. This gradient was proposed to be formed by
coupling the translocation of protons across the membrane to electron transfer reactions
between electron transport complexes of those membranes. The electrochemical
potential formed in this process was then utilized for the synthesis of ATP.

The chemiosmotic theory was initially received with little enthusiasm. However,

during the 1970s, as evidence accumulated in favor of this hypothesis, the Situation
gradually changed. By the middle of 1970s, the principle of Mitchell’s theory was
accepted by most investigators in that field and he was awarded the Nobel Prize for
Chemistry in 1978. However, the mechanistic details of how an electron couples to the
proton still remains undefined.2 The major objective of this dissertation is to elucidate
how electrons and protons are coupled by designing and synthesizing new

supramolecules which feature integrated electron and proton transfer networks.
A. PCET in Photosystem II

Photosystem II (PSII) is a transmembrane protein that effects a transverse flux of
electrons and protons. It consists of at least ten protein subunits.3 However, all the
electron-flow events in PS 11 take place via prosthetic groups bound to only two
polypeptides, namely L and M branches, which form the actual reaction center of PS 11.
These two protein subunits are highly hydrophobic integral proteins of about 32 Kda in
the thylakoid membrane. They contain the pigments, redox systems, and other
components involved in the light driven redox reaction across the membrane: P680, two
monomeric chlorophylls a , two pheophyrins, two plastoquinones, and an iron bound via
four histidines (Figure 1). The primary light event‘ takes place at the chlorophyll dimer
(P680) that is bound via two histidines (His 198) to two homologous proteins. When the
reaction center P680 is excited, charge Separation occurs in 10 ps and the electron is
passed from the excited primary electron donor P°680 onto a primary electron acceptor, a
pheophytin. The pheophytin in turn reduces the first plastoquinone (Q A) to a

semiquinone in about 1 ns. The semiquinone reduces the second plastoquinone (QB),

 

 

BPh BPh proton

 

 

 

 

 

translocation

"3:33 M Branch .

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

r? R

2H*+1lzoz 112 H20

Figure 1. PCET in Photosystem II (PSII)

which is bonded loosely to the b1 protein subunit. The oxidized P680 is reduced to its
initial state by the manganese complex of the oxygen evolve system (OES) after charge
separation.

After a second Similar excitation cycle, QB accepts a second electron, concomitant
with proton transfer from the external protein matrix to form a hydroquinone. The
plastohydro-quinone leaves the quinone-binding pocket and diffuses to the lumen side,
where it is later oxidized to a quinone by Cyt b6t.5 The protons in the CBC are released
into the inner lumen space of the thylakoid membrane, resulting in a net effect of proton
transport opposite to the direction of electron flow across the membrane. In this way, the
proton gradient is established between the inner and outer Spaces of the thylakoid
membrane and results in a proton chemical potential that drives the proton dependent

adenine triphosphate (ATP) synthesis.
B. PCET in cytochrome c oxidase

In biological systems, the ET pathway is carefully controlled to reach maximum
energy efficiency. The recent breakthrough in determination of the three dimensional
structure and electron transfer rates in cytochrome c oxidase reveals that the PCET
reaction plays a central role in controlling the route of intermolecular electron transfer in
the reaction center of this enzyme. As described in Figure 2, when an electron is injected

into CuA of the fully oxidized enzyme, it initially equilibrates with heme a at a rate

constant of 104 S".6 The reduction of heme a3 occurs at much Slower rate of 1-100 s",

depending on the experimental conditions.7 Consequently, the electron-transfer rates

from CuA to heme a and a3 , respectively, differ by 2-4 orders of magnitude. This result

is perplexing inasmuch as recent high-resolution three-dimensional structures of

CuA

 

 

Figure 2. Electron transfer pathways and rates in cytochrome c oxidase

cytochrome c oxidases from Paracoccus denitrificans8 and bovine heart9 reveal that the

distances from CuA to hemes a and a3 are similar (19.5 and 22.1 A, respectively). The

relatively small difference in distances cannot alone account for the large difference in
the electron transfer rate between CuA and the two hemes, and suggests a more
complicated operative mechanism.

Indeed, electron transfer from heme a to heme a3 displays complex pH

dependence10 and the experimental results suggest that this electron transfer is kinetically

coupled to the proton released from a site in the vicinity of heme a3. This group interacts
more strongly with heme 613 than with heme a and is buried inside the protein, in contact

with the bulk protons of a proton-conducting pathway.” The maximum proton

release/uptake at heme 613 was found to be ~0.7 H+/e'. These results are consistent with

the three dimensional P. denitrificans structure which Shows that a larger number of

prontonable groups are found around heme a3 than near heme a. On the basis of these

results, Brzenski12 has suggested that electron transfer from CuA to heme a is
accompanied by a smaller proton-charge compensation than that associated with electron

transfer to heme a3 , thereby accounting for the rate difference between the two pathways.

A similar situation has been found on the acceptor side of the photosynthetic
reaction center (e. g. from Rhodobacter sphaeroide), where the direct electron transfer
rate from the electron donor (P) to QB is much Slower than that from P to Q A, even though
both distances and driving forces are similar.13 This difference in rate has been found to
be due to a difference in the reorganization energies, with the QA reorganization energy
being smaller than that associated with QB. In this case, QB interacts more strongly with

protonable groups, resulting in a net proton uptake (0.4-1.0 H1/QB') upon electron transfer

from Q A to Q13 in the reaction center.”

In support of this contention, reorganization energies associated with the electron
transfer processes have been estimated from temperature dependent studies.12 It has been
found that when proton uptake is involved, the reorganization energy increases
significantly. The reorganization energy A for the electron transfer from CuA to heme a

is 0.3 eV and that for the direct electron transfer from CuA to heme a3 is 0.8 eV. The
larger reorganization energy associated with heme 03 over heme a explains why the
direct electron transfer from CuA to heme a3 is much slower than the transfer from CuA to

heme a .

II. Strategies for PCET design

A. Overall design

The above examples demonstrate how proteins control the intramolecular ET
pathway through their special three-dimensional structures by utilizing the PCET reaction.
To unravel the PCET mechanism, several problems needed to be explored such as: Is the
proton and electron transfer concerted? Do they transfer stepwise and which transfer is
first? What structural/electronic properties establish consecutive versus concerted PCET?
How will the proton transfer rate depend on the electron transfer rate? What
structural/electronic features of the proton interface are important in governing the
coupling between the electron and the proton? Owing to the complexity of biological
systems, the important factors that affect the PCET reaction are difficult to isolate.
Therefore, we have chosen to study biomimetic model compounds, which have the

advantage that specific properties of the complex can be tuned by proper design and

synthesis. Synthetic analogs may lead to greater understanding, which is difficult or even
impossible to elucidate by using biological systems.

The basic strategy for designing our model complexes is to combine
photoelectron transfer through a fixed distance with that of photoinduced proton transfer.
This strategy lends itself to two design types (Figure 3). One such design is to channel
the electron transfer through a proton interface, in which the proton transfer is internal to
the electron transfer pathway. In this type of design, an electron donor and acceptor pair
is juxtaposed by a proton transfer interface to feature a donor-proton interface-acceptor
arrangement. Another design is to locate the proton interface at the terminus of the
electron transfer pathway, either on electron donor or acceptor. In this design, the proton
transfer is external to electron transfer (PT external to ET). This arrangement of the
electron donor, acceptor and proton interface is analogous to that in the photosynthetic

reaction center and cytochrome c oxidase.
B. Donor-Acceptors

Although electron transfer has been actively pursued for decades, the study of the
role of protons on the electron transfer events has only recently gained interest.15 We
have decided to adapt the well-understood fixed-distance electron donor/acceptor strategy
to our design of PCET model compounds. Porphyrin and chlorin compounds are
particularly attractive ET D/A systems and have been considered as the primary electron
donor-acceptor in our study. Upon photo-irradiation, excited states of porphyrin and
chlorin are accessed and they become good electron donors. Their redox properties can
be tuned by changing the metal (the oxidation potential increase in the order Mg” < Zn”

< H22+ < H,4+ <Sn"+),“5 providing various driving forces for electron transfer. Systems

 

>

ET

PT

[H]

PCET

Figure 3. PCET design

10

based on porphyrin and chlorin molecules have been well studied.17 The synthesis,
electron transfer rates, transient absorption spectra, driving forces and electronic
couplings of various systems have been well documented. This large amount of
information is of great use in the exploration of new PCET chemistry based on these

systems.
C. Porphyrin model compounds for ET studies

Porphyrin complexes have been widely used in building model compounds that
resemble the natural pigments of enzyme reaction centers. Osuka et al.18 have developed
a model for the photosynthetic reaction center. Complex 1 consists of three porphyrins
with an individual benzoquinone attached to the terminal porphyrin. Two porphyrins are
stacked to act like the special pair dimer in photosynthetic systems. The authors showed
by picosecond transient optical spectroscopy19 that rapid electron transfer occurs between
the porphyrin and quinone that are adjacent to one another. This electron transfer may be
followed by a second dark electron transfer from the dirneric porphyrin to the central
porphyrin, although the evidence for this reaction is not particularly strong. The
assignment of transient absorption spectra to the various oxidized and reduced species in
this series is complicated by broad, indistinct Spectra and by similarities between spectra
of the exited states and the ionic states.

1.20

To resolve the problem, Osuka et a have prepared the same type of porphyrins,
but the benzoquinone acceptor has been replaced with pyromellitimide (2). The
pyromellitimide radical anion possesses a distinct, narrow optical transition at 715 nm

that is diagnostic of charge separation. For the simple porphyrin-pyromellitimide donor-

acceptor pair in THF, the forward electron transfer occurs with a rate constant of

11

“@322.
eye 0 3&0

93 R? Pl
1.R=Q 2.R= —m¥\/\N

1.7 X 1010 3", while the ion pair recombines with a rate constant of 9.3 X 109 s". The free
energy of this reaction is about 0.5 eV. The authors observed two-step electron transfer
in this complex. Strong interactions between the two sandwiched porphyrins results in
lowering of the SI energy by 0.19 eV and the correspondingly oxidation potential by 0.17
eV. The pyromellitimide radical anion absorption decays biexponentially with lifetimes
of 70 ps and 2.5 ns.

Sessler et al.21 have examined an interesting porphyrin-quinone in which the
porphyrin is associated with the quinone by means of a Watson-Crick base pairing
cytosine- guanine hydrogen bonded linkage. The formation of the hydrogen bond was
characterized by 1H NMR (Km = 13,000 M‘1 in dichloromethane). ET kinetics between
a Zn-porphyrin and benzoquinone was determined by using a fluorescence quenching
technique. Association of the quinone causes moderate quenching (I = 710 ps) of the 1.8
ns Zn-porphyrin excited state lifetime. From the quenching rate constant, the

unimolecular ET rate constant was determined to be 8.6x 109 s' . This approach is

appealing because it permits photoinduced electron transfer to be probed in a system in

12

which the electronic coupling between the donor and acceptor is transmitted across weak

hydrogen bonds.

 

To investigate the passive role of protons in modulating of electron transfer, Turro
et al.22 have built a model complex in which a Zn-porphyrin and 3,4-dinitrobenzene are
linked via a hydrogen bond interface of a carboxylic acid dimer (3). Electron transfer
processes were examined by picosecond transient optical Spectroscopy. It was found that
rate constants for both charge separation and charge recombination of this donor acceptor
system were '5.0x10‘° s‘1 and 1.0><10lo s", respectively. The rates are comparable to those
of covalently linked Zn-porphyrin/acceptor systems with similar separations and driving
forces.23 This study showed that hydrogen bond interface is competitive to covalent bond
linkages. Moreover, the deuterium isotope effect of kH/kD = 1.7 and kH/kD = 1.6 for
charge separation and charge recombination respectively, revealed that electron transfer

was coupled to proton motion.

l3

4

Gust et al.24 have extensively explored carotenoid-porphyrin-quinone triads to
achieve long-lived charge separation in these supramolecular systems. Excitation of the
carotenoid-porphyrin-quinone triad yields the porphyrin's first excited singlet state, which
decays by electron transfer to give a C-P”-Q" charge-separated state. Competing with
the rapid charge recombination is the electron transfer from the carotenoid that produces
a long-lived C7-P-Q" species. Various efforts25 have been made to tune the electronic
and thermodynamic factors so that forward electron transfer is favored over charge

26 a PCET reaction has been applied to achieve long-lived

recombination. Recently,
charge separation. The naphthoquinone moiety of 5 is fused to a norbomene system
bearing a carboxylic acid at a bridgehead so that an intramolecular hydrogen bond from
the carboxyl group to the nearby quinone carbonyl can form. Electron transfer from the
photoexcited porphyrin results in a marked pKa increase at the quinone, leading to a
proton shift from the acid to the quinone, which generates a new state with a reduced
recombination rate. The effect of the proton is significant. The quantum yield of the
final charge-separated state of 5 is 2 fold higher relative to the reference triads 6 and 7

and the life-time of final charge-separated state for 5 is much longer than those for 6 and

7 (233 nS vs. 62 and 60 ns, respectively).

 

5. R2: Q1

6. R2 = 02 R3: H

7. R2: 02 R3 = Cl

C. Proton interfaces

1. Amidinium-carboxylate salt bridge:

To establish the directionality of proton transfer, it is advantageous to use
asymmetric proton interfaces.27 One such proton interface is formed by the association of
an arnidine to a carboxylic acid (Schema). It can be viewed as a model of the
aspartane-arginine salt bridge, which is an important feature found in many structures
including RNA stem loops,28 zinc finger/DNA complexes”, and the active site of

dihydrofolate reductase.30 However, unlike the guanidinium-carboxylate interaction of

15

Arg-Asp, amidinium Shows only one specific binding mode for carboxylate, which

simplifies PCET studies.
H H
\N—H O \N-H --------- O
\ I \
i <\ + > l; —> H“ elrf—S
N H-O N—H --------- O
/ /
H H

Scheme 1

Due to the primary charge interaction and two favorable secondary electrostatic
interactions (Figure 4), this proton interface is predicted to be very stable according
Jorgenson’s hydrogen bond theory.“ Indeed, the binding is so strong that it can occur
even in polar solvent such as DMSO.27 The association constant measured for the salt
bridge formed from bicyclic guanidinium-carboxylate is over 105 in chloroform.32 This

stability ensures the persistence of proton interface in PCET reactions.

H
\N‘“ ------ Q: + _
1‘6) 1’
/N-H ----- (:3 O I + X -
H

Figure 4. Secondary electrostatic interactions in amidinium-carboxylate salt bridge

Electron transfer through the amidinium-carboxylate asymmetric interface has

been initially investigated for 8 and 9.27b The donor in 8 and 9 is electronically excited

16

Ru(II)(trnbpy)32+ (trnbpy = tetramethybipyridine) and the acceptor is a dinitroaromatic.
Thus, a comparison of 8 and 9 allows the investigation of the directionality of electron

transfer through the asymmetric interface.

   

N02

In both cases, lifetime quenching measurements Show a biexponential decay in
which one lifetime component is concentration dependent and the other is concentration
independent. The concentration-dependent rate constant is assigned to birnolecular ET
processes and the concentration-independent rate constant is attributed to ET for the
associated pairs shown by 8 and 9. The ET rate through the proton interface for 8 (8.4
x 10° s") is found to be slower than that for 9 (3.10 x 108 s"). It is believed in 8, the ET
event drives the proton movement thus greater reorganization energy is associated with
the proton interface. This is not the case in 9, where the proton is already residing on the

acceptor and is likely to remain upon the arrival of the electron.
2. Schiff base:

Schiff bases are attractive proton interfaces external to the ET pathway. For

l7

instance, protonation/deprotonation reactions of the retinal Schiff base species in situ in
rhodopsin” and in bacteriorhodopsin34 have been intimately associated with the proton-
pumping reactions of these proteins. In addition, these reactions may be relevant to those
that occur for heme a in its involvement in proton pumping in the mitochondrial protein
and cytochrome oxidase.35

In proteins, the physical and chemical properties of the porphyrin system can be
modulated by interactions between its peripheral substituents and nearby amino acid side
chains. The Schiff bases Show versatility owing to the fact that both formations of the
linkage and its subsequent protonation may be subject to functional control. Schiff base
porphyrin 10 have previously been prepared and characterized by optical and Raman

36 Upon protonation, the deep red Schiff base turns deep green and the

spectroscopies.
404 nm Soret band splits to give rise to 377 and 432 nm bands. In addition, the Q-band
shows a dramatic shift from 577 to 620 nm. The C=N stretching frequency exhibits a
strong resonance enhancement and it shows the typical red Shift with the protonation of

the Schiff base. These properties provide a unique way to detect proton motion in a

PCET study.

SUN

10

18

III. Results and Presentation

Porphyrin, purpurin and chlorin modified with amidinium or carboxylate groups
have been synthesized. These compounds are used for the study of PCET with the proton
transfer interface internal to the ET pathway. The formation of donor/acceptor pairs via
an amidinium-carboxylate salt bridge has been fully characterized by X-ray
crystallography, ‘H NMR and UV-vis spectroscopies. Utilizing UV-vis spectroscopy, we
have been able to establish the electronic interaction between the proton interface and
chromophore. As discussed in Chapter 111, Chapter IV and Chapter V, preliminary
electron transfer results reveal that in coupled systems, the proton coupling has a
significant effect on the ET rate.

In this dissertation, Chapter II describes the synthesis of porphyrins equipped with
amidinium or carboxylate functional groups. Strategies to improve the solubility of these
types of molecules and to couple and decouple the proton interface from the porphyrin
ring are also presented. Chapter 111 describes the characterization of the amidinium-
carboxylate salt bridge and the study of association constants of this salt bridge. In
Chapter IV, an improved coupled/decoupled system based on purpurin/chlorin structures
has been synthesized. ET results indicate that the proton is coupled to electron transfer
within the amidinium-carboxylate interface. Chapter V describes the synthesis of water
soluble porphyrin-quinone complex. In this supramolecule, the porphyrin contains
hydrophilic functional groups that enable ET to be performed in aqueous solution. ET

studies reveal that protonation occurs upon ET from porphyrin to quinone.

Chapter II

Synthesis of Porphyrins Modified with

Amidinium and Carboxylic Acid Groups

I. Introduction

Previous studies of ET through symmetric carboxylic acid dimer interfaces have
shown that the proton can mediate ET rates.22 However, theoretical studies37 indicate that
the proton displacement on one side of the carboxylic acid dimer interface is
compensated by displacement of a proton from the other side. Changes in polarity,
charge, and energetics resulting from proton motion within the interface are not easily
distinguished in the ET rate. This is not the case in amidinium-carboxylate interfaces. In
this asymmetric proton interface, the directionality of electron transfer as perturbed by
proton motion can be assessed. Furthermore, the asymmetric interfaces provide
specificity in binding. The acceptor can only bind to the donor, which is not the case for
symmetric interface in which there are also acceptor-acceptor and donor-donor bindings.

As we stated in Chapter I, the salt bridge can form by association of an amidine to

a carboxylic acid. However, the amidine is a strong base (e.g. pKa of acetamidine is

19

20

found to be 12.40 in water”) and can be easily protonated to form amidinium under most
experimental conditions. Consequently, it is more convenient to make this salt bridge
from amidinium and carboxylate. Hence, to obtain the electron donor/acceptor pair
juxtaposed by this salt bridge, we need to synthesize donors and acceptors modified with
amidinium or carboxylate groups. When the donor amidinium mixes with the acceptor
carboxylate, an amidinium-carboxylate salt bridge is formed in such a way that the
protons are on the donor side. To switch this proton interface, we can mix the donor
carboxylate with acceptor amidinium to form a salt bridge in which the protons are on the
acceptor side. In the first case, the proton can move from a donor to an acceptor upon
electron transfer, whereas in the second case, the proton is already on the acceptor side
and is expected to remain there upon arrival of the electron. This construct therefore
allows us to study the effects of proton motion on the electron transfer rate.

The goal of the work described in this Chapter is to synthesize porphyrins
modified with either amidinium or carboxylate. In order to investigate whether the
electronic interaction between the electron and proton interface is important to PCET
reactions, two types of structures have been designed. In one such structure, the
amidinium or carboxylate group is directly attached to the porphyrin moieties. This
places the proton interface in n-conjugation with the porphyrin. Through this
conjugation, changes at the proton interface can affect the electronic structure of the
porphyrin and the electron transfer can affect the proton interface. Thus, the porphyrin
and proton interface are coupled in this design. In another design, a mesa-phenyl group
is inserted between the porphyrin ring and amidinium or carboxylate group. X-ray

structure analyses has shown that the mesa substituted phenyl group is usually

21

perpendicular to the porphyrin ring, especially when adjacent ,6 positions are substituted
owing to steric congestion.” This orientation minimizes the conjugation between the
phenyl and porphyrin moieties and thus, the electronic coupling between the proton
interface and porphyrin.

A convenient method to make amidiniums is from nitriles. There are two
common methods to convert a nitrile to an amidinium (W). The Pinner
synthesis40 is a two-step reaction, transforming nitriles into irnido esters, which are
generally isolated, and then condensed with ammonia or an amine in a separate step.
Alternatively, Garigipati’s‘" utilizes an amide transfer reagent42 to convert a nitrile to an
amidinium in one step with high yield. Recently, this synthesis was applied successfully
in our lab to make Ru(bpy)27 and porphyrin acryl amidinium.43 The disadvantage of this

method is that the functional groups such as carbonyl and nitro groups can also react with

the amide transfer reagent. Hence in these cases, the Pinner synthesis is applied.

 

Pinner Synthesis:
NH NH Cl NH
/ 4
j—CEN + ROH = g C\/ _. of .HC.
OR NHZ
Garigipati Synthesis:
'- /NH2 7
('31 S——C\\ H20 ”NH
S—CEN + A|\ —’ N ’ ch 'HC'
/
H2N CH3 A1 NH2
_ CI’ ‘CH3 _

 

 

Scheme 2

22

In the case that nitrile can not be directly accessed, it has to be transformed from
other derivatives such as aldehyde, ester or amide. Olah’s synthesis44 provides a
convenient method to convert aldehyde to nitrile in one step using hydroxyamine
hydrochloride in formic acid. The synthesis from ester and amide is not suitable for
porphyrins because the reaction condition involves alcohol as solvent, in which most
porphyrins are usually insoluble. Since carboxylic acids can also be synthesized from the
oxidation of aldehydes, the synthesis of our target molecules conveniently begins with

the synthesis of porphyrin aldehydes.

II. Synthesis

A. Porphyrin phenyl amidinium and carboxylic acid—decoupled systems

1. First generation:

The strategy for synthesizing porphyrin phenyl aldehyde 27 is based on Sessler’s
synthesis of porphyrin-porphyrin-quinone triad.“ In this approach, two aldehyde groups
on the phenyl ring are introduced sequentially. The first aldehyde is for synthesizing
dipyrrylrnethane, which may be condensed to give a porphyrin. The second aldehyde
group, which is planed to introduce afier the porphyrin, will lead the formation of the
amidinium group. As described in Scheme_3, 4-carboxy-benzaldehyde was converted to
its ethyl ester 11 by reacting with ethanol under acid catalysis. The aldehyde group of 11
was protected by converting to acetal 12, which was then reduced with lithium aluminum
hydride to give the alcohol 13, as a precursor of the second aldehyde group. Under acid-
catalyzed reaction, acetal 13 was converted to aldehyde 14 in situ and reacted with ethyl

3-ethyl-4-methylpyrrole-2-carboxylate 19, which was synthesized by following the

23

procedure of Barton-lard“, to give dipyrrylmethane 20 in 75% yield. The resulted 20
was then saponified and decarboxylated using a method reported by Chang47 to give Ot-
free dipyrrylmethane 21 in 95% yield.

In SchmeA, ethyl 4-ethyl-3,5-dimethylpyrrole-2-carboxylate was quantitatively
transformed by oxidation with lead tetraacetate to the 5-acetoxymethyl analogue 22,
which was self-condensed in hot 70% aqueous acetic acid to form the diethoxycarbonyl
dipyrrylmethane 23. The ethyl ester group of the dipyrrylmethane 23 was saponified and
decarboxylated using the previous procedure to give compound 24 in quantitative yield.
Diformyl-dipyrrylmethane 25 was obtained by treating 24 with the Vilsmeier reagent,
which was generated in situ by the addition of POCl3 to DMF. This gave the other half
moiety needed for making porphyrin 26. Reaction of 25 with dipyrrylmethane 21
underwent a MacDonald condensation to give porphyrin 26 in 47% yield.

The further transformation of porphyrin 26 is described in Schemej. Oxidation
of porphyrin 26 with PDC in CHzCl2 gave the corresponding porphyrin phenyl aldehyde
27 in 75% yield. Employing the procedure of Olah, 27 was converted to nitrile 28 in one
step with hydroxyamine hydrochloride in refluxing formic acid with 88% yield. IR
spectrum of this porphyrin showed a moderate absorption at 2235 cm", which is the
characteristic absorption of CN group. The route from nitrile to arnidine is based on the
original approach of Garigipati.“1 Porphyrin 28 was first converted to its nickel complex
29 to protect the porphyrin ring from aluminum insertion. Treatment of nickel porphyrin
phenyl nitrile 29 with chloromethylaluminum amide42 in toluene at 80 °C gave 30 in 85%

yield. Afier isolation, the arnidine group was found in the protonated amidinium form.

24

CH0 CH0

EtOH HO OH

 

H+ H+
COOH 002Et

11

 

NaOHl
HOCHchZOH

CHZOH

 

Scheme 3

O
O

COzEt
12

mm,

O
1‘——
O

CHZOH

25

 

 

PbtA00)2 70% HOAc
———r> ____,
/ \ AGO / \
N COZEt N COzEt
H H
22
NaOH/CZH4(OH)2
/ \ / \ = / \ / \
Etozc N N COZEt N N
H H H H
23 24
POCI DMF CHZOH
3’ s / \ / \
OHC N N CHO
H H
25

 

Scheme 4

26

This is supported by proton NMR, in which NH protons appear as two broad peaks at
9.26 and 9.68 ppm; integration indicates that they are in 1:1 ratio and each peak contains
two protons. Nickel porphyrin 30 was then demetallated with concentrated sulfuric acid
to give free base 31 in quantitative yield. Zinc insertion was accomplished by reacting 31
with ZnCl2 in DMF and iron porphyrin 33 was made by the standard method“. I

The synthesis of porphyrin phenyl acid 37 was achieved in an analogous manner
(Schemej). Acid-catalyzed condensation of pyrrole 19 with 4-carboxybenzaldehyde
gave dipyrrylmethane 34 in 69% yield. The ester group of 34 was then saponified and
decarboxylated to give 35 in 90% yield. This di-OI free dipyrrylmethane was condensed
with diformyl-dipyrrylmehane 26 to give porphyrin phenyl acid 36 in 48% yield. Free
base porphyrin 37 was obtained by treating 36 with dilute HCl solution followed by
neutralization with sodium bicarbonate aqueous solution. The corresponding iron(III)
porphyrin 38 and nickel porphyrin 39 were then synthesized from 37.

2. Second generation — with improved solubility:

For the formation of hydrogen bonds, a low polar solvent such as acetonitrile,
dichloromethane or chloroform should be chosen. These have low dielectric constants
and the hydrogen bond is expected to be stable. Unfortunately, the solubility of
porphyrins made above in these solvents is very low. For ET study, especially by
transient absorption detection, relatively concentrated samples are required. We found it
was necessary to modify the peripheral substituents of porphyrins in order to improve
their solubility.

Various functional groups have been used to improve porphyrin solubility in

27

CH20H CHO

CN
PDC NHz -HC|/
—--——> -———>
HCOOH

26 27 28

Ni(AoO)2
or

+ +
H2N NH; HzN NH; CN

0 0

C'TA'I' NH2
1. H2304 CH3
5. N8C03

31 30 29

 

ZnC|2 FeBrz/T HF

 

Scheme 5

28

 

 

 

 

EtOZC COZEI
34
NaOHI
COOH HOCHZCHZOH
0 71 71
OHC N N CHO
H H
4 26
1PTSA
22n(AcO)2
3 p-chloranil
36 35
HCI
COOH COOH COOH
Ni(AoO)2
———>
37 39

 

Scheme 6

29

organic solvents,49 one of which is long chain alkyls. We initially tested this approach on
porphyrin phenyl acid because it can be synthesized in a reasonable number of steps. To
introduce long chain alkyls to a porphyrin molecule, we needed to initially synthesize a
pyrrole substituted with such chain alkyls. As described in Schema, 1-iodo-octane
reacted with 1,4-pentadione to form 3-acetylundecane-2-one 40. Compound 40 was then
condensed with OI-oximinoacetoacetate under Knorr’s pyrrole conditions to give 42.
Pyrrole 42 underwent oxidation and self-condensation to form dipyrrylmethane 44. After
saponification and decarboxylation, 45 was obtained and then treated with the Vilsmeier
reagent to give diformyl-dipyrrylmethane 46. The 2+2 McDonald condensation of 46
and 36, using conditions described for making 38, gave octylporphyrin phenyl acid 47 in
25% yield. Unfortunately, the use of long chain alkyls showed no Significant
improvement on the solubility of 47 compared to porphyrin 38.

Another approach for increasing porphyrin solubility involved the incorporation
of bulky substituents. In some cases, the poor solubility of porphyrins is caused by
intermolecular aggregationf0 which may be circumvented by the steric hindrance of
bulky groups. In 1995, Therien’l synthesized 5-carboxyphenyl-10,15,20-tris(3’,4’,5’-
trimethoxyphenyl)-porphyrin to study the electron transfer through the carboxylic acid
dimer interface. This porphyrin exhibited good solubility in CHzClz. Considering the
poor solubility we experienced for porphyrin phenyl acid, it was thought that porphyrin
modified with trimethoxyphenyl groups may have enhanced solubility. Therefore, we
decided to incorporate such groups in our porphyrin structure.

We tested this idea with porphyrin 48, which contained one trimethoxyphenyl

group because it was easily accessible through a one step reaction. As shown in

30

 

 

POClalDMF

 

7

Coca
/\ /\
N N
H H

 

o O n-CaH17I CB
M w
0 O
40 anHAcO Cg
r——> / \
N C02EI
o O H
o O NaNOz 42
M --> .
0E1 N
‘OH
41 Pb(AoO)2
C3 C8 C8
70% HOAc
/ \ / \ : A00 / \
E10 N N CO Et N CO E1
2C H H 2 H 2
44 43
1 NaOWCzH4(OH)2

c, c,
/ \ / \
OHC CHO

Z
:2

 

 

45
COOH
Ca Ca

47

Ca = n-C3H17

Scheme 7

31

7

Schemfl, under conditions originally proposed by Chang,4 and later optimized by
Lindsey,52 a 1:1:1 mixture of 3,4,5-trimeyhoxybenzaldehyde, dipyrrylmethane 25, and 4-
carboxylic benzaldehyde condensed in the presence of TFA to give a mixture containing
three porphyrins. This mixture was separated by careful chromatography on Silica gel.
Porphyrin 48, the desired porphyrin, was obtained in 26% yield. It was then converted to
its corresponding iron and zinc complexes. All forms of porphyrin phenyl acid Showed
good solubility in dichloromethane.

Encouraged by this success, the same strategy was employed to make porphyrin
phenyl amidinium 54. AS described in Schemefl, the cross condensation of a 1:121
mixture of 3,4,5-t1imethoxybenzaldehyde, dipyrrylmethane 25 and 4-cyanobenzaldyde
also gave a mixture of porphyrins, from which 51 was separated and obtained in 36%
yield. After nickel insertion, porphyrin phenyl nitrile 52 was converted to its
corresponding amidinium 53 using the amide transfer reagent, C1A1(NH2)CH3. The
nickel porphyrin 53 was subsequently transformed into its zinc and iron complexes via
free base 54. Again, the trimethoxyphenyl group Showed a dramatic enhancement in the

solubility and all forms of porphyrin phenyl amidinium compounds showed satisfactory

solubility.
B. Porphyrin amidinium and carboxylic acid—coupling system

To introduce an amidinium group directly on the porphyrin ring, we initiated the
synthesis of meso-formyloctaethylporphyrin, from which meso-cyanooctaethylporphyrin
was made by using the Olah’s method. However, our attempt to convert the nitrile to
amidinium was unsuccessful, presumably due to the steric hindrance at the mesa position.

For this reason, we decided to shift the amidinium group to a ,B—position, where it was

32

less sterically encumbered. The synthetic strategy used here was to introduce an
aldehyde group at fl-position first. Then the aldehyde could be converted to a nitrile and
then an amidinium group by using the methodology established previously. In addition,
carboxylic acid derivatives could be synthesized from the aldehyde by oxidation, to
generate another moiety for the proton interface. The first step in the synthesis of the
porphyrin aldehyde was the synthesis of pyrrole 58 (SchemeJQ). Ethyl bromoacetate
reacted with 2,4-pentadione to give 57, from which 58 was synthesized by employing
Knorr’s pyrrole condensation. Pyrrole 58 was brominated with bromine to give
bromomethylpyrrole 59, which condensed with ethyl 3,4-dimethylpyrrole-2-carboxylate
to form dipyrrylmethane 60. The ethyl acetate Side chain of the dipyrrylmethane 60 was
selectively reduced with diborane to form the hydroxyethyl derivative 61. The ester
groups of 61 was then sponified and decarboxylated by heating with sodium hydroxide in
ethylene glycol to give compound 62, which was one half of the target of porphyrin 66.

To synthesize the second half of porphyrin 66, 3,4,5-trimethoxybenzaldehyde
reacted with pyrrole 19 in the presence of an acid catalyst to give dipyrrylmethane 63 in
62% yield. Compound 63 was saponified and decarboxylated to form di-a free dipyrryl-
methane 64. After treatment with the Vilsmeier reagent, 64 was converted to its diformyl
derivative 65. Compound 62 and 65 were condensed in a “2+2” pattern under McDonald
conditions to generate porphyrin 66 in 56% yield (Schemfll).

The transformation of 66 to porphyrin aldehyde 70 was described in Schemelz.
The hydoxyethyl porphyrin 66 was chlorinated with the Vilrneier reagent to give
chloroethyl porphyrin 67. Vinyl porphyrin 68 was obtained by treating 67 with DBU in

refluxing pyridine. In the previous study, Chang49 found that the vinyl group could be

33

OMe
MeOQCHO + / \ / \ + OHC—Q—COOH
MeO ” u
25
1.TFA
12.0hloranil

MeO
O
O O
OH
MeO

48
mm» / \ Fear.

 

Scheme 8

34

I

MeO MeO
Ni(AcO)2
M... O Q ~—-» O O c~
MeO M60
51 52
lClsArNHz
CH3
MeO MeO
NH; 1112804 NH;
O O <—— O O -
NH2 2.N82C03 NHz Cl
MeO MeO
54 53

lhcww N

 

55 56

Scheme 9

35

 

 

 

 

Br CB
0 0 O OEt .,
'——> COzEt
O O Zn/HOAc
57 ‘r > / \
N 002Et
H
O O 58
J
I OEt
Ns
OH Br2/CCI4
41
if
002Et 302‘: fi com
A 19
EtOC N N COEt N COEt
2 H H 2 H 2
so 59
32H6
HO Ho
NaOH/CZH4(OH)2
/ \ / \ 7 / \ / \
EtOZC N N 002151 N N
H H H H
61 62

Scheme 10

36

MeO
MeO CHO + / \

N COZEI
MeO H

19

 

 

 

 

 

HO
OMe
MeO OMe
/ \ / \ O
N N
H H
62
H0
66

Scheme 11

37

conveniently converted to an aldehyde with osmium tetraoxide/sodium periodate. In this
case, the OSO4 reaction was carried out in dichloromethane using one equivalent Of
osmium tetraoxide (per porphyrin) in the presence of pyridine. This reaction had to be
monitored carefully because prolonged reaction time caused side reactions, giving
unidentified products. Maximum yields were obtained when the reaction was allowed to
stir for 30 min. The resulting osmate ester was then treated with hydrogen sulfide to give
porphyrin diol 69. When the solution containing diol 69 in pyridine was treated with 5%
sodium periodate, a precipitate formed and it was identified as porphyrin aldehyde 70.
The yield for the conversion from 69 to 70 was ahnost quantitative.

Both carboxylic acid porphyrin 71 and amidinium porphyrin 75 were derived
from aldehyde 70 (W). Oxidation of 70 with Jone’s reagents3 at 0 °C effected the
conversion of aldehyde 70 to carboxylic acid 71, as confirmed by both MS and NMR
spectrum. Porphyrin 71 was then transformed to its zinc complex 72. To make
amidinium 75, porphyrin 70 was first converted to porphyrin nitrile 73 by using
hydroxyamine hydrochloride in refluxing formic acid. After nickel insertion, 74 was
converted to 75 using ClAl(NH2)CH3. The amidinium porphyrin 75 was fully
characterized by MS (FAB) and NMR, in which two characteristic peaks for NH protons
of the amidinium group were observed at 6.82, 10.88 ppm with 1:1 ratio. Nickel
porphyrin 75 was then converted to zinc complex 77 via free base 76 following the same

procedure described previously. All porphyrins showed good solubility in CHzClz.

OMe

MeO OMe

66 OH

OMe

MeO OMe

H0
69

OH

Na|04l
pyridine

GHQ

70

38

OMe

MeO OMe

POCIg/
DMF
DBUI
pyridine
OMe
Mac I OMe
1. 0804
2. H23
<-———

Scheme 12

39

 

OMe
MeO I OMe
CN

, NHZOH HCI/
formic acid
73
l Ni(AcO)2
OMe
MeO I OMe
CN
NH2
Ill / toluene
H3C' \Cl
OMe
MeO l OMe
75. M = N1
76. M t 2H
77. M =- Zn
H2*N NH;
Cl'

Scheme 13

MeO

I OMe

CHO

Cr03, H2304/
Acetone

IM OMe

MeO

71

COOH
l Zn(AcO)2

OMe

MeO OMe

72

COOH

40

III. Properties

A. Coupling eflects

UV-vis spectroscopy was used to probe the coupling between porphyrin
chromophore and proton interface. The absorption spectrum of porphyrin amidinium 75
Showed strong pH dependence. Significant Spectral changes were observed upon
protonation/deprotonation of the arnidine group using acid/base. Figure 5 Shows the
spectral changes of 75 in the presence of various concentrations of DBU in CHZCIZ. With
the addition of this base, the porphyrin Soret band blue-Shified 7 nm (from 406 to 401 nm)
and the Q band blue-Shifted 9 nm (from 575 to 564 nm). Isosbestic points were
maintained at 405 and 569 nm. Similar spectral changes were observed upon addition of
other strong bases such as sodium methoxide and butyllithium. Furthermore, this process
was found reversible and the original spectrum could be recovered when CH2C12
saturated with HClO4 was added. The perturbation of the absorption profile upon
protonation suggests that the porphyrinic chromophore of 75 is strongly coupled to the
amidinium functional group and correspondingly the proton interface.

Conversely, when strong bases such as DBU were added to porphyrin 53, which
contained a phenyl spacer, only minor changes were observed (Figure 6). The
conversion of amidinium to arnidine had little effects on the electronic structure of the
porphyrin. This independence of spectroscopic profile of 53 from the deprotonation of
amidinium indicates that the porphyrinic chromophore is electronically decoupled from

the amidinium group.

41

 

2.5

Abs.

 

 

 

 

350 400 450 500 550 600 650

Figure 5. Absorption spectral changes of 75 upon addition of DBU in CHZCI2 (The

amount of DBU increase with arrows)

42

 

Abs

 

 

 

 

.350 400 450 500 550 600 650

A (nm)

Figure 6. Absorption spectral of 53 in the absent (—) and the presence of 3.00 eq. DBU
( ....... ) in (:I..IZC:12

43

B. [R studies

IR spectra were recorded for porphyrin amidinium 75 and its deprotonated form,
namely, porphyrin amidine. Spectra are shown in Figure 7. In both cases, porphyrin ring
vibrations remain unchanged, indicating that the blue shift of porphyrin Spectra of 75
upon deprotonation is due to the electron withdrawing decrease of the amidine group and
no redox change of the porphyrin n-system is involved. Previous IR and Raman
spectroscopy studies54 of arnidine have established that the C=N stretching frequency is
in the 1620-1700 cm’1 region. Accordingly, the peak at 1635 cm'1 (Figure 7b) is assigned
to the C=N stretch of arnidine. In the protonated form, the C=N stretching frequency of
amidinium (Figure 7a) Shifts to 1670 cm“. Similar changes in the C=N stretching
frequency due to the protonation/deprotonation were also observed in other Simple
arnidine compounds” (protonation of acetoamidine to acetoamidinium shifts the C=N
stretching frequency from 1650 to 1690 cm") and Schiff base compounds,’6 whose C=N
stretching frequency displays 30-80 cm‘l blue shifis upon protonation. Theoretical
calculations indicates that the protonation of nitrogen cause rehybridization of its orbitals.
As a result, more nitrogen s-orbital participates in the formation of C-N bond, which
gives a stronger C-N bond and higher force constants7 This diagnostic change in C=N
stretching frequency of amidinium upon protonation/deprotonation should allow us to

detect proton motion within the amidinium-carboxylate interface.

Transmmitance

44

 

‘14

'13

12

 

 

1A

 

(19

(18

 

07

 

 

06 1 L i l l l 1 14 l 1 I i I I I l l I I 14 I l l L l I l

3500 3000 2500 2000 1500 1000

 

wavenumber (cm’l)

Figure 7. IR spectra of 75. (a) protonation form, (b) deprotonation form

45

IV. Experimental

Materials and measurements. Reagents and solvents for synthesis were used as
received unless otherwise stated. CHzCl2 and DMF were distilled from Cal-12. THF and
toluene were freshly distilled from Na/benzophenone. Proton NMR spectra were
recorded on Varian Gemini-300 in CDCl3 (Cambridge Isotope laboratories) with the
residual CHCl3 as the internal standard set at 7.24 ppm. UV-vis spectra were measured
on a Cary-17 spectrophotometer. Mass Spectra were measured from a benchtop VG Trio-
] mass Spectrometer. F AB-MS were obtained from a JEOL HX-l 10 HF double focusing
Spectrometer operating in the positive ion detection mode. Infrared spectra were obtained
from coating samples on a KBr plate and recorded on a Nicolet IR/42 Spectrometer.

Analytical TLC was performed by using Eastman Kodak 13181 (100 pm thick) silica gel

Sheets. In column chromatography, 60-200 mesh silica gel was used.

WWW

4-Carboxybenzaldehyde (15.0 g, 0.10 mol) was dissolved in ethanol (100 m1).
Concentrated H2804 (1 ml) was added and the mixture was heated to reflux. After 1 h,
the mixture was added to 200 g of ice and white precipitates formed. The mixture was
neutralized by addition of sodium bicarbonate and the solid was collected by filtration
and was washed with water and dried in air to give 11 in 67% yield (12 g, 0.067 mol).
mp. 65-67 °C; 1H NMR (300 MHz, CDC13): 5 1.37 (3H, t, COZCHZCH3), 4.33 (2H, q,
COZCHZCH3), 7.66 (4H, dd, aromatic), 10.5 (1H, CHO); MS found m/e 178, calcd.

178.06 for CmHmO3.

46

WW

A 250-ml round-bottomed flask equipped with a reflux condenser was charged with 11
(8.9 g, 0.05 mol), ethylene glycol (31 g, 0.5 mol) and benzene (150 m1). p-
Toluenesulfonic acid (0.15 g) was added and the mixture was heated to reflux until no
more water was collected in the water collector. The reaction mixture was then cooled,
washed with sodium bicarbonate solution, saturated sodium chloride solution and water,
dried over sodium sulfate. The solvent was removed to give 9.5 g product (86% yield).
1H NMR: 5 1.32 (3H, t, COZCHZCH3), 4.05 (4H, m, CH2CH2), 4.35 (2H, q, COZCHZCH3),

5.83 ( 1H, s, CH), 7.76 (4H, dd, aromatic); MS found m/e 222, calcd 222.09 for CIZHMO4.

W

A solution consisting of 12 (9.5 g, 0.043 mol) and lithium aluminum hydride (4.86 g,
0.128 mol) in 150 dry THF was stirred overnight at room temperature under nitrogen.
Ethyl acetate (50 ml) was added dropwise to quench the reaction and the mixture was
filtered to remove the solid residue. The filtrate was added to water and was extracted
with methylene chloride several times. The organic layer was combined, dried over
sodium sulfate and the solvent was removed to give 6.14 g product (81% yield). 1H
NMR (300 MHz, CDCl,): 5 1.80 (1H, t, OH), 4.10 (4H, m, CHZCHZ), 4.70 (2H,d,
2112011), 5.81 (1H, s, CH), 7.45 (4H, dd, aromatic); MS found m/e 180; calcd 180.08 for

CIOHl203‘

D. - - . 1 - - . .
n - u. - 01H ‘- t --u o --ouu -10 0.101 Ni ii la! I

A 250-ml round-bottomed flask equipped with a reflux condenser was charged with

47

acetal 12 (6.14g, 34.1 mmol), ethyl 3,4-dimethylpyrrole-2-carboxylate (12.33 g, 68.2
mmol), and 130 ml of absolute ethanol. A few drops of concentrated HCl were added,
and the solution was refluxed under nitrogen with stirring. At the end of this time, TLC
(silica gel, 20% EtOAc/hexane eluent) indicated the absence of starting material. The
solvent was removed under reduced pressure, and the red oil was loaded onto a silica gel
column. Elution with 20% EtOAc/hexane yielded the product as a pale yellow oil.
Drying under high vacuum gave 20 as a pale yellow solid (11.5 g, 23.9 mmol) in 73%
yield. 1H NMR (300 MHz, CDCl,): 8 1.10 (6H, t, CHZCH3), 1.31 (6H, t, COZCHZCH3),
1.79 (6H, s, CH3), 2.72 (4H, q, CH2CH3), 4.24 (4H, q, COzflIZCH3), 4.70 (2H, d,
CHZOH), 5.48 (1H, s, CH3), 7.33 (4H,dd, aromatic), 8.24 (2H, 8, NH); MS (CI 70eV),

m/e= 480, calcd 480.26 for C23H36N205.

A 250-ml round-bottomed flask equipped with a reflux condenser was charged with 20
(11.5 g, 0.0239 mol), 120 ml of ethylene glycol, and 12 g of sodium hydroxide pellets.
The reaction mixture was refluxed overnight under nitrogen. After cooling of the

solution to room temperature, water was added and the precipitate was filtered off,
washed with H20, and dried to afford the pure 21 (11.62 g, 0.022 mol) in 92.8%. 1H
NMR (300 MHz, CDCl,): 8 1.17 (6H, t, CHZCH3), 1.79 (6H, s, CH3), 2.42(4H, q,
CHZCH3), 4.68 (2H, s, CHZOH), 5.49 (1H, (1, CH), 7.21 (4H, dd, phenyl-H), 6.38 (2H, s,

CH), 8.5 (2H, br, NH); MS found mle= 336, calcd 336.22 for szstNzo-

9 '_ ' 9 ' - 9 ' _ _ -
-I n. .101 - - ,1 - ‘-on I - -ou| u .10..

48

Lead tetraacetate (378 g, 0.69 mol) was slowly added with stirring, to a solution of ethyl
4-ethyl-3, 5-dimethylpyrrole-2-carboxylate (135 g, 0.69 mol) in HOAc (700 ml). The
mixture was then warmed on a steam bath for 10 min before being poured into water (2 l).
The precipitate was filtered, washed, and dried to give 22, which was used directly for the
next step without further purification.

The crude acetoxy compound was dissolved in 1500 ml of hot HOAc. The mixture was
heated to reflux and water (300 ml) was added. The mixture was reflux for additional 10
min, poured into water (2.5 l) and left standing overnight, undisturbed. The precipitate
was filtered, washed, and crystallized from methanol/water to give 115 g of the title
compound (89%). mp. 109-110 °C; 1H NMR (300 MHz, CDCl,): 5 1.05 (6H, t,
CH2£H3), 1.30 (6H, t, COZCH2CH3), 2.25 (6H, s, CH3), 2.40 (4H, q, CHZCH3), 3.85 (2H,
s, CH2), 4.25 (4H, q, C02CH2CH3), 8.95 (2H, br, NH); MS found rn/e 374, calcd 374.22
for C21H3ONZO4.

, o , ' ,

Dipyrrylmethane diester 23 (11.1 g, 0.03 mol) from the last step was saponified and
decarboxylated with sodium hydroxide in refluxing ethylene glycol under conditions
described for 21, to give 6.8 g of 24 (98%). 1H NMR (300 MHz, CDCl,): 8 1.10 (6H, t,
CHZCH3), 2.05 (6H, s, CH3), 2.45 (4H, q, CHZCH3), 3.85 (2H, s, CH2), 6.38 (2H, S, a-H),

7.42 (2H, br, NH); MS (CI 70eV), m/e 230, calcd 230.18 for C,,H,,N,.

 

A solution consisting of 24 ( 4.6 g, 0.020 mol) in DMF ( 30 ml) was cooled below 5 °C.

49

Benzoyl chloride (5 ml) was added dropwise over 10 minutes to the solution while
maintaining the temperature below 5 °C. The solution was stirred at this temperature for
20 min, and then allowed to stir at room temperature for 1 hour. Aqueous ethanol (50 ml,
50%) containing sodium carbonate (10 g) was added and the mixture was warmed on a
steam bath for 15 min. Water was added until all the sodium carbonate residue dissolved.
After 4 hours at room temperature, the precipitate was collected and recrystallized from
95% ethanol to give 25 ( 4.4 g, 0.010 mol) in 77% yield. mp. 205-206 °C; lH NMR (300
MHz, CDCl,): 6 1.10 (6H, t, CHZCH3), 2.30 (6H, s, CH3), 2.45 (4H, q, CHZCH3), 3.95
(2H, s, CH2), 9.50 (2H, S, aldehyde), 10.50 (2H, br, NH); MS found m/e 286, calcd

286.17 for C,,H,,N,O,.

-'-. ..,...-. ..-. .: ‘m‘t - :--mu-. umm ~
A 500 ml round-bottomed flask was charged with 21 (1.018 g, 2.96 mol), 5, 5’-
diformyl-dipyrrylmehane 25 (1.0 g, 2.96 mmol), and 320 ml of THFzMeOH (2:1). The
reaction mixture was purged with N2, covered with foil, and 1.0 ml of HClO4(aq) was
added with stirring. The reaction was allowed to stir in the dark for 12 h, after which 0-
chloranil (1.2 g) was added and the reaction was stirred for an additional 12 h. The
reaction mixture was poured into brine and extracted several times with methylene
chloride. The organic layers were combined, washed with NaHCO3(aq) and H20, and
dried over Na2S04. The solvent was removed on a rotary evaporator to give dark solid.
After chromatography on silica gel (2% MeOH/CH2C12 eluent), the title compound (812
mg, 1.39 mmol) was isolated in 46.9% yield. m.p. >275 °C; UV-vis: Am, 404, 503, 536,

569, 622 nm; 1H NMR (300 MHz, CDCl,): 5 -3.50 (1H, s, NH), -3.35 (1H, 5, NH), 1.72,

50

1.86 (6H each, t, CHZCH3), 2.42, 3.62 (6H each, s, CH3), 4.1 (8H, m, CHZCH3), 5.18 (2H,
s, CH2), 7.88 (4H, m, aromatic), 9.92 (1H, S, mesa), 10.14 (2H, s, mesa); MS found m/e

584.2, calcd 584.35 for C,,H,,N,O.

-'- IIII ll'l -i --m_‘I - :"Ic_ll’fl III-IuI

A 250 ml round-bottomed flask was charged with porphyrin 26 (584 mg, 1.00 mmol),
freshly distilled CHZCI2 (100 ml), and PDC (1.01 g, 2.7 mmol). The reaction mixture was
allowed to stir for 3 h under nitrogen, at which time TLC (2% MeOIl/CH2C12 eluent)
indicated the complete conversion of starting material into product. The reaction mixture
was poured into brine and extracted several times with CHzClz. The organic layers were
combined, washed several times with H20 and dried (N a2S04). After evaporation, the
product was purified by chromatography on silica gel (2% MeOH/CH2C12 eluent) to give
the titled compound in 80% yield. m.p. >270 °C; UV-vis: Am 401, 505, 536, 569, 630
nm; 1H NMR (300 MHz, CDCl3): 8 -3.30 (1H, S, NH), -3.15 (1H, 8, NH), 1.72,1.86 (6H
each, t, CHZCH3), 2.43, 3.64 (6H each, s, CH3), 4.05 (8H, m, CHZCH3), 8.40 (4H, m,
aromatic), 9.96 (1H, s, mesa), 10.18 (2H, s, mesa), 11.95 (1H, s, aldehyde); MS found

m/e 582, calcd 582.34 for C39H42N4O.

-' el'll'l -1-‘I._‘I- 1-' 40‘! III-Int
A lOO-ml round-bottomed flask equipped with a reflux condenser was charged with
porphyrin aldehyde 27 (232 mg, 0.40 mmol), hydroxyamine hydrochloride (200 mg, 1.4

mmol) and 10 ml of 95% formic acid. The reaction mixture was heated at reflux

overnight under nitrogen atmosphere. The solution was cooled to room temperature and

51

poured into water. It was then neutralized with sodium bicarbonate before being
extracted several times with methylene chloride. The organic layers were combined and
washed with water twice. Alter drying over sodium sulfate, the solvent was removed on
a rotary evaporator and the resulting solid was chromatographed on silica gel
(dichloromethane eluent) to give 28 (198 mg, 0.34 mmol) in 85% yield. m.p. >270 °C;
UV-vis: Am, 402, 505, 536, 570, 630 nm; 1H NMR (300 MHz, CDCl,): 6 -3.30, -3.15 (1H
each, s, NH), 1.76, 1.82 (6H each, I, CHZCH3), 2.40, 3.62 (6H each, s, CH3), 4.05 (8H, m,
CHZCH3), 8.12 (4H, m, aromatic), 9.96 (1H, s, mesa), 10.18 (2H, S, mesa); MS found m/e

579, calcd 579.34 for C,,H,,N,.

‘5 -'- ..Iu-r -! —‘I._'.I - :-'!«.“‘I IIIIIIII

A 100-ml round-bottomed flask equipped with a reflux condenser was charged with
porphyrin 28 (115 mg, 0.2 mmol) and DMF (20 ml). The reaction mixture was refluxed
until chelation was completed (monitored by both UV-vis and TLC, ca. 1 hours). Water
was added, followed by dichloromethane. The organic layer was washed several times
with water. After removal of solvent, the solid residue was chromatographed on Silica

(eluted with dichloromethane) to give 29 (116 mg, 0.18 mmol) in 91% yield. m.p. >270

°C; UV-vis: Am 399, 521, 556 nm; MS found m/e 635; calcd 635.26 for C39H39N5Ni.

U .‘ M‘IIIIIJOOU'I - : -‘I-.‘I - :-'.o..H'.l IIIIIIII
chloridfilll
To a solution of porphyrin 29 (116 mg, 0.18 mmol) in dry toluene (15 ml), was added a

solution of chloromethylaluminum amide (2.0 M in toluene, 1.0 ml). This solution was

52

heated at 80 °C for 48 h under argon atmosphere. The reaction mixture was cooled and
the aluminum complex was decomposed by carefully pouring the solution into a slurry of
silica gel (5 g) in chloroform. The mixture was stirred for 5 min and the silica gel was
filtered. The filtercake was further washed with methanol. Evaporation of the filtrate
and purification of the residue by chromatography on silica gel (25% methanol in
dichloromethane) afforded the title compound (96 mg, 0.15 mmol) in 82% yield. m.p.
>270 °C; UV-vis: Am 398.0, 521.0, 556.0 nm; lH NMR (300 MHz, DMSO- 6): 8 1.58,
1.73 (6H each, I, CHZCH3), 2.23, 3.45 (6H each, s, CH3), 3.85 (8H, m, CHICH3), 8.15 (4H,
m, aromatic), 9.26, 9.68 (2H each, S, NH2 of amidinium), 9.70 (1H, S, mesa), 9.76 (2H, S,

mesa); MS (FAB) found m/e 653.2 for (MHI), calcd 653.29 for C39H43N6Ni.

“W... "nu _: “h... _ :__h"_. ”n”... H'.._
31

Concentrated H2SO4 (2 ml) was added to nickel porphyrin 30 (80 mg, 0.122 mmol). The
reaction mixture was stirred at room temperature for 1 h before diluted carefully with ice.
The solution was then neutralized with NazCO3 and the porphyrin was collected by
filtration. The crude product was chromatographed on a silica (30% MeOH in CHZCIZ)

afforded 72 mg of 31 (96%). mp. >270 °C; UV-vis: Am, 402, 501, 535, 570, 623 nm.

Zinc 5i4i-ll.'.l. IIII‘I - : -‘Ir'I - :-'Iv.“'.l IIIIIIII
chlmidrcfiz
Zinc chloride (0.1 g) in methanol was added to a solution of porphyrin 31 (20 mg, 0.0335

mmol) in 10 ml of DMF. The mixture was heated at 60°C until the zinc insertion was

53

complete (monitored by UV-vis). Then water was added, followed by CHzClz. The
organic layers was separated and washed with water several times and dried over Na,SO4.
After evaporation of solvent, the crude product was purified on TLC plate (20% MeOH

in CH,C1,) to give 20 mg of 32 (90%). mp. >270 °C; UV-vis: Amax 406, 536, 571 mm

1H NMR (300 MHz, DMSO-dg): 8 1.58, 1.73 (6H each, t, CHZCH3), 2.23, 3.45 (6H each,
s, CH3), 3.85 (8H, m, CHZCH3), 8.20 (4H, m, aromatic), 9.40, 9.70 (2H each, s, NH2 of
amidinium), 9.75 (1H, S, meso), 9.80 (2H, s, mesa); MS (FAB) found m/e 659.2 for

(MI-F), calcd 659.28 for C39H43N62n.

Iron (.4-..°"..,....-. - : 3...». - :-..__..-. .......
bromidsjfl

Iron(II) bromide (50 mg, 0.23 mmol) was added to a solution of porphyrin fiee base 30
(30 mg, 0.050 mmol) in anhydrous THF containing pyridine (10 drops). The mixture
was refluxed under nitrogen for 1h. The solvent was removed under reduced pressure
and the residue was chromatographed on a column of silica gel. The first and second
fractions eluting from the column contained iron porphyrin and its u-oxo dimer,
respectively, and were combined. The solution was treated with 2 M HBr, dried over
NaZSO4 and brought to dryness under vacuum to give iron porphyrin 33 (31 mg, 0.038
mmol) in 76% yield. UV-vis: Am 389, 511, 641 nm; MS (FAB) found 651.1 for (Fe-

porphyrin + H), calcd 651.29 for C39H43N6Fe.

I‘ - . . . - . -
u - II. . III -- I --II I --Ou| ‘- II. 2.... III II Io...

4-Carboxybenzaldehyde (1.5 g, 0.01 mol) was condensed with ethyl 3, 4-dimethylpyrrol-

54

2-carboxylate (3.6 g, 20.0 mol) under conditions described for 20, yielding 3.8 g (69%)
of the title compound. m.p. >270 °C; 1H NMR (300 MHz, CDCl3): 8 1.10 (6H, t,
CHZCH3), 1.31 (6H, t, COZCHZCH3), 1.39 (6H, t, COZCH29H3), 1.79 (6H, s, CH3), 2.74
(4H, q, CHZCH3), 4.26 (4H, q, COZCH2CH3), 4.38 (4H, q, COZCHZCH3), 5.53 (1H, s,
CH3), 7.18, 8.10 (2H each, d, aromatic), 8.28 (2H, S, NH); MS found m/e 522, calcd

522.27 for C30H38NZO6.

Dipyrryhnethane 34 (3.8 g, 6.88 mmol) was treated with sodium hydroxide in ethylene
glycol under conditions described for 21, yielding 2.16 g of the titled compound (90%
yield). 1H NMR (300 MHz, CDCl,): 8 1.17 (6H, t, CHZCH3), 1.79 (6H, s, CH3), 2.42 (4H,
q, CH2CH3), 5.49 (1H, s, CH3), 6.38 (2H, S, OI-H of pyrrole), 7.12, 7.30 (2H each, d,
aromatic), 8.50 (2H, 8, NH); MS found m/e 350, calcd 350.20 for C22H26N202.

'1 -"-.m.u1'1 -I -'l(’-.‘| - :-’|~.II'I IIIIIIII I

A 500 ml round-bottomed flask was charged with 35 (1.05 g, 3.00 mmol), 25 (0.86 g,
3.00 mmol) and 300 ml of dry dichloromethane. The reaction mixture was purged with
nitrogen, covered with alumna foil, and was added a solution of p-toluenesulfonic acid
hydrate (2.0 g) in methanol (36 ml). The reaction was allowed to stir in the dark for 12 h,
before adding a saturated solution of zinc acetate in methanol (32 ml). After 12 h, p-
chloranil (1.2 g) was added and the reaction was stirred for an additional 12 h. The
reaction mixture was neutralized with NaZCO3 and poured into brine and extracted

several times with CHzClz. The organic layers were combined, washed with water and

55

dried with Na2804. The solvent was evaporated on a rotary evaporator to give a dark
solid. After chromatography on silica gel (4% MeOI-l/CHZCI2 eluent), the product (960
mg, 1.45 mol) was isolated in 48% yield. m.p. >270 °C; UV-vis: Am, 404, 534, 570 nm;
1H NMR (300 MHz, CDCl3/CD3OD): 8 1.72, 1.81 (6H each, CHZCH3), 2.32, 3.62 (6H
each, s, CH3), 3.98 (8H, m, CHZCH3), 8.22 (4H, m, aromatic), 9.92 (1H, s, mesa), 10.04
(2H, s, meso); MS found m/e 660, calcd 660.24 for C39H40N402Zn.

I. -'-. II.‘II‘I -1 -’lq'l - :-‘lqll‘t IIIIIIII

To a solution of zinc porphyrin 36 (132 mg, 0.2 mmol) in 10% MeOH/CH2C12 (30 ml)
was added 10% HCl(aq). The mixture was stirred for 20 min and neutralized with
saturated sodium bicarbonate solution. The organic layer was then washed with water
and dried with Na2804. The solvent was removed under reduced pressure to give 120 mg
of free base 37 .

The porphyrin 37 (60 mg, 0.1 mmol) was treated with FeBr2 in THF under condition
described previously, giving 45 mg of iron(III) porphyrin 38 (70%). mp. >275 °C; UV-

vis: Am 389, 511, 641 nm; MS found m/e 652, calcd 652.25 for C39H40FeN4OZ.

‘. ,- .' ._ .c,‘..-. -1 -‘l-_‘_l - :-‘|-."‘.I IIIIIIII

Nickel insertion of 37 (60 mg, 0.1 mmol) was accomplished by using Ni(AcO)2 in DMF
following the procedure described before, affording porphyrin 39 (53 mg, 0.080 mmol) in
80% yield. m.p. >275 °C; UV-vis: Am, 400, 522, 558 nm; MS found m/e 654, calcd

654.25 for C39H40N4Ni02.

56

In a 3000 ml 3-necked flask were placed anhydrous potassium carbonate (75 g, 0.50 mol),
potassium iodide (15 g, 0.09 mol), 2-butanone (100 ml), 2, 4-pentanedione (50 g, 0.50
mol) and l-iodooctane (120 g, 0.50 mol). On heating to reflux, the reaction became
violent and the heating had to be withdrawn. When the reaction had subsided, it was
refluxed for 4 hours using hot water bath. The reaction mixture was diluted with acetone
and the salts were filtered off and washed further with acetone. The filtrates were
concentrated under vacuum and the oil was distilled under reduced pressure to give the
title compound as light yellow oil (53 g, 0.25 mol, 43% yield). b. p. 110°C-112 °C/15

mmHg.

Ethyl acetoacetate (31.2 g, 0.20 mol) in glacial acetic acid (30 ml) was cooled in an ice
bath. Sodium nitrite (14.0 g, 0.20 mol) in water (15 ml) was added dropwise over 1
hours with stirring. The resulting solution of ethyl at-oximinoacetoacetate 41 was added
dropwise, along with zinc dust (326 g, 5.0 mol), to a stirred solution of 40 ( 42.0 g, 0.20
mol) in acetic acid (1200 ml) over 1 hour. The temperature was kept under 80 °C during
the reaction process. After the addition, the reaction was allowed to stir for 0.5 h. Then
the mixture was decanted in cold water and left overnight. The resulting solid was
filtered off and washed with tap water. The filter cake was dissolved in dichloromethane
and filtered to remove the zinc dust. The organic phase was evaporated in vacuo and the
solid was crystallized from methanol/water to give product as white crystals (22.3 g, 0.08

mol, 40% yield). 1H NMR (300 MHz, CDCl,): 8 0.88 (3H, t, CH3 of octyl), 1.25 (12 H,

57

m, CH2 of octyl), 1.32 (3H, t, COZCHZCH3), 2.15, 2.25 (3H each, 8, CH3), 2.30 (2H, , t,
CH2). 4.32 (2H, q, C02§H2CH3), 8.50 (1H, 8, NH); MS found m/e 279, calcd 279.22 for

C17H29N02-

’-'- L ,_... _ 1.". . _ _H. _ ._- u‘ u, '9'-
Pyrrole 42 (22.3 g, 0.08 mol) from the last step was converted to 44 via its acetoxymethyl
derivative 43 following the procedure described for making 23, yielding 17.3 g of
product (80% base on 42). . mp. 101-102 °C; IH NMR (300 MHz, CDCl,): 8 0.85 (3H, t,
CH3 of octyl), 2.12 (3H, t, COzCHzCH3), 1.20 (12H, m, CH2 of octyl), 2.20 (3H, S, CH3),
2.25 (2H, t, CH2 of octyl), 3.75 (2H, s, CH2), 4.15 (2H, q, COZCHZCH3), 8.80 (2H, S,

NH); MS found m/e 542, calcd 542.42 for c,,H,,N,O,.

9 ' 9 ' 9

Dipyrrylmethane 43 (16.2 g, 0.30 mol) from the last step was saponified and
decarboxylated with sodium hydroxide in refluxing ethylene glycol using conditions
described for 21, generating 9.8 g of product (82%). lH NMR (300 MHz, CDCl,): 8 0.82
(3H, t, CH3 of octyl), 1.30 (12H, m, CH2 of octyl), 2.00 (3H, s, CH3), 2.38 (2H, t, CH2 of

octyl), 3.78 (2H, s, CH2), 6.34 (2H, S, at-H of pyrrole), 7.34 (2H, S, NH); MS found m/e

398, calcd 398.37 for C27H46N2.

 

Dipyrryhnethane 45 (4.0 g, 0.01 mol) was forrnylated with the Vilsmeier reagent

generated in situ by addition of POCl3 to DMF using conditions described for 25, to

58

afford 4.1 g of the title compound (88%). mp. 157-158 °C; 1H NMR (300 MHz, CDCl3):
8 0.82 (3H, t, CH3 of octyl), 1.30 (12H, m, CH2 of octyl), 2.25 (3H, s, CH3), 2.40 (2H, t,
CH2 of octyl), 3.90 (2H, s, CH2), 9.50 (2H, S, aldehyde), 10.64 (2H, 8, NH); MS (CI 70
eV), m/e 454, calcd 454.36 for C29H46N202.

- _v_.,,,.‘,,., _ ;.., - ;_.,,,,-, _ -..° ,5 ”u”...
Condensation of 45 (1.37 g, 3.00 mmol) with 25 (0.86 g, 3.00 mmol) using conditions
described for 36 afforded 620 mg dioctylporphyrin 47 (25%). mp. >275 °C; UV-vis:
Am 403, 534, 571 nm; 1H NMR (300 MHz, CDCl3/CD3OD): 8 0.85 (6H, t, CH3 of octyl),
1.40 (24H, m, CH2 of octyl), 1.72 (6H, t, CHZCH3), 2.32, 3.62 (6H each, s, CH3), 3.98
(4H, m, CHZCH3), 4.05 (4H, t, CH2 of octyl), 8.22 (4H, m, aromatic), 9.92 (1H, s, mesa),

10.04 (2H, s, mesa); MS found m/e 830, calcd 828.43 for C,,H,,N,O,Zn.

9 9 '
'99."...‘01'. ' "

A 100 ml round-bottomed flask was charged with 4-carboxybenzaldehyde (0.75 g, 5.0
mmol), dipyrrylmethane 25 (2.30 g, 10.0 mmol), and 3,4,5-trimethoxybenzaldehyde
(1.00 g, 5.0 mmol) in freshly distilled dichloromethane (200 ml). The reaction mixture
was purged with nitrogen, covered with foil, and trifluoroacetic acid (0.4 ml) was added
with stirring. The reaction was allowed to stir in the dark for 12 h. Before being
neutralized by the addition of sodium acetate (2.5 g). After which p-chloranil (1.5 g, 6.1
mmol) was added and the reaction stirred for an additional 12 h. The solvent was

removed under reduced pressure to give a dark solid. Chromatography on silica gel

59

(dichloromethane first, then 4% methanol in dichloromethane), first eluted 5, 15-
bis(3’,4’,5’-trimethoxyphenyl)porphyrin, followed by desired porphyrin 48 (0.98 g, 26%).
mp. >275 °C; UV-vis: Am, 408, 506, 540, 573, 625; 1H NMR (300 MHz, CDCl,): 8 -
2.25 (2H, s, NH), 1.85 (12H, m, CHZCH3), 2.50, 2.65 (6H each, s, CH3), 3.90 (6H, S, m-
OCH3), 4.00 (8H, m, CHZCH3), 4.20 (3H, s p-OCH3), 7.32 (2H, S, aromatic), 8.25, 8.55
(2H each, d, aromatic), 10.25 (2H, s, mesa proton); MS found m/e 764, calcd 764.39 for

C48H52N4Os-

' I_ . - I 0-. _ _ ._ 99 9- ' . .
I - q 09.100 I I I .1.’ I." 19.1.0l " -

Saturated zinc acetate in methanol (0.5 ml) was added to a solution of free base 48 (76
mg, 0.1 mmol) in dichloromethane (20 ml). The mixture was heated reflux for 20 min
and then the solution was washed with water and dried over sodium sulfate. After
evaporation of solvent, the residue was chromatographed on silica gel (4% methanol in
dichloromethane) to give 80 mg of zinc porphyrin 49 (96%). mp. >275 °C; UV-vis: Am,

411, 539, 573; MS found m/e 826, calcd 826.32 for C48H50N405Zn.

9 9 ' - .

The iron insertion was accomplished by using the F eBrz/T HF method described
previously, yielding iron porphyrin 51 in 75% yield. m.p. >275 °C; UV-vis: Am 390,

512, 642 nm; MS found m/e 818, calcd 818.31 for C,,H,,N,O,Fe.

9 9 ' _ .
'II" 10.1091 " '

Cross condensation of 4-cyanobenzaldehyde (0.65 g, 5.0 mmol), dipyrryhnethane 25
(2.30 g, 10.0 mmol), and 3,4,5-trimethoxybenzaldehyde under conditions described
previously afforded 1.34 g porphyrin 51 (36%). mp. >275 °C; 1H NMR (300MHz,
CDCl,): 8 -2.30 (2H, S, NH), 1.85 (12H, m, CHZCH3), 2.40, 2.65 (6H each, S, CH3), 3.90
(6H, S, m-OCH3), 4.00 (8H, m, p-CHzCH3), 4.20 (3H, s OCH3), 7.30 (2H, s, aromatic),
8.00, 8.20 (2H each, d, aromatic), 10.25 (2H, s, mesa proton); MS found 745, calcd

745.40 for C,,H,,N,O,.

9 9 ° . _
"I" 19.1.. I ' -

Free base 51 (370 mg, 0.5 mmol) was treated with nickel acetate under condition
described previous, yielding 315 mg of nickel porphyrin 52 (78%). mp. >275 °C; UV-

vis: 4...: 407, 527, 563; MS found m/e 801, calcd 801.32 for C,,H,,N,Nio,.

Nickel W'qHWOIJIII‘I - : i-‘II'I -0- "’ I'Ill‘t0.llt'l -
321“} ll 1'1] .153

Nickel porphyrin 52 (160 mg, 0.20 mmol) was treated with chloromethylaluminum
amide (1 ml, 1.0 mmol) under conditions described before, giving 147 mg of porphyrin
amidinium chloride 53 (86%). mp. >275 °C; UV-vis: Am 408, 528, 563; lH NMR (300
MHz, CDCl3): 8 1.5, 1.55 (6H each, t, CH2CH3), 2.10, 2.35 (6H each, s, CH3), 3.56, 3.64

(4H each, q, CH2CH3), 3.80 (6H, s, m-OCH,), 4.21 (3H, s p-OCH3), 7.08 (2H, s,

61

aromatic), 8.04, 8.20 (2H each, d, aromatic), 8.32, 10.02 (2H each, S, NH of amidinium),
9.40 (2H, s, mesa proton); MS (FAB) found m/e 819.3 (MH+), calcd 819.35 for

c,,H,,N,o,Ni.

Zinc 544-meme

Porphyrin 53 was demetallated using concentrated sulfuric acid under conditions

 

described previously to give free base 54. The zinc insertion of the free base was
accomplished by using the ZnClz/DMF method described previously, giving zinc
porphyrin 55 in 95% yield. m.p. >275 °C; UV-vis: Am, 411, 539, 573; MS (FAB) found

m/e 825.2 (MH+), calcd 825.35 for C48H53N603Zn.

SZISIZ- 11 1.11.153

Free base 54 (22.0 mg, 0.030 mmol) was treated with F eBr2 in THF under conditions

 

described previously, affording 18.0 mg of iron porphyrin 56 (73%). m.p. >275 °C; UV-

vs: 390, 512, 642; MS (FAB) found 817.5 (MH+), calcd 817.35 for C48H53N603Fe.

In a 3-1 3-necked flask were placed anhydrous potassium carbonate (415.08 g, 3 mol),
potassium iodide (90.3 g, 0.54 mol), 2-butanone (100 ml), 2, 4-pentanedione (308 ml, 3
mol) and ethyl chloroacetate (367.5 g, 3 mol). On heating to reflux, the reaction became

violent and the heating was withdrawn. When the reaction subsided, it was refluxed for 4

62

hours. The reaction mixture was diluted with acetone and the salts were filtered off and
washed further with acetone. The filtrates were concentrated in vacuo and the oil was
distilled under reduced pressure to give the product as light yellow oil (236 g, 1.3 mol,
43% yield). b.p. 140°C-145°C/15mmHg; 1H NMR (300 MHz, CDCl3): two tautomers
was observed: 1) for keto: 5 1.12 (3H, t (J = 7.5 Hz), COZCHZCH3), 2.15 (6H, s, CH3),
2.74 (2H, d (J =8.0 Hz), CH2), 4.00 (1H, t (J = 8.0 Hz), CH), 4.01 (2H, q (J= 7.5 Hz),
COZCHZCH3), 2) for enol form: 5 1.11 (3H, t (J = 7.5 Hz), COZCHZCH3), 2.04 (6H, s,
CH3), 3.14 (s, 2H, CH2), 4.01 (2H, q (J= 7.5 Hz), COZCHZCH3); MS (C170 eV), m/e 186,

calcd 186.09 for C9H14O4.

1 ‘-‘ u. ._ nu 11‘1 - «115: 1". - - 4,10. .. ‘ .'
Ethyl acetoacetate (237.6 g, 1.50 mol) in glacial acetic acid (300 ml) was cooled in an ice
bath, sodium nitrite (103.8 g, 1.50 mol) in water (145 ml) was added dropwise over 2
hours with stirring. The resulting solution of ethyl a-oximinoacetoacetate was added
dropwise, along with zinc dust (326 g, 5.0 mol), to a stirred solution of ethyl 3-acetyl-4-
oxopentanoate (279 g, 1.50 mol) in acetic acid (1200 ml) over 1 hour. The temperature
was kept under 80 °C during the reaction process. After the addition, the reaction was
allowed to stir for 0.5 hour. Then the mixture was decanted to pour into cold water and
left standing overnight. The resulting solid was filtered off and washed with tap water.
The filter cake was dissolved in dichloromethane and filtered to remove zinc dust. The
organic phase was evaporated in vacuo and the solids were recrystallized from
methanol/water to give the pyrrole as yellowish crystal (177.1 g, 0.70 mol, 46% yield).

m.p. 116-117 °C; 1H NMR (300 MHz, CDCl3): 5 1.21 (3H, t, COzCH2QH3), 1.32 (3H, t,

63

COZCHZCH3), 2.21, 2.25(3H each, s, CH3), 3.34 (2H, s, CH2), 4.13 (2H, q, COZCHZCH3),
4.25 (2H, q, COZQHZCHs), 8.82 (1H, 5, NH); MS found m/e 253, calcd 253.13 for

c,,H,,No,.

0 '00u0II‘I --“IO. e000 0“! --l|’l INCH-4.00.
In a 500-ml Erlenmyer flask, ethyl 4-ethoxycarbonylmethyl-3,4-dimethyl pyrrole-2-
carboxylate (12.7 g, 0.050 mol) was dissolved in carbon tetrachloride (70 ml) and was
heated to 50 °C. A solution of bromine (8.0 g, 0.050 mol) in carbon tetrachloride (32 ml)
was added dropwise. Afler addition was complete, a precipitate was formed and the
mixture turned reddish color. It was kept stirring at 50 °C for 2 more hours and then
refrigerated for overnight. The precipitate was collected by filtration and the resulting
solid was recrystallized from chloroform/hexane to give the product (8.77 g, 0.026 mol)
in 53% yield. 'H NMR (300 MHz, CDCl3): 6 1.23 (3H, t, C02CHZCH3), 1.34 (3H, t,
COZCHZCH3), 2.27 (3H, s, CH3), 3.46 (2H, s, CH2), 4.13 (2H, q, COZCHZCH3), 4.32 (2H,
q, COZCHZCH3), 4.55 (2H, s, CHzBr), 9.44 (1H, s, NH); MS found m/e 331, calcd:331.06
for C13H18NO4Br.

. 9 '_ 9 9 ° _ 9 ' _ .
- U0. ._ DUI ll U - "1.. -., 00. - -II" I - '0010. N 01..

6.0

A 250-ml round-bottomed flask was charged with 2-ethoxycarbonyl-3,4-dimethyl pyrrole
(3.34 g, 0.020 mol), concentrated HCl (0.30 ml) and methanol (32 ml). Pyrrole 59 (6.6 g,
0.020 mol) in 60 ml methanol was added dropwise while heating to 60 °C. Once

addition was completed, it was refluxed for 10 min and a precipitate formed. The

64

reaction mixture was then refrigerated for 2 h. The precipitate was collected by suction
filtration and washed with small amount methanol to give the title compound (6.68 g,
0.016 mol) in 80% yield. 1H NMR (300 MHz, CDCl,): 8 1.30 (3H, t, COZCHZCH3), 1.34
(6H, t, C02CHZCH3), 2.02, 2.25, 2.29 (3H each, s, CH3), 3.71 (2H, s, CH2C02CH2CH3),
4.88 (2H, s, CH2), 4.26 (6H, m, COZQHZCH3), 9.15, 9.98 (1H each, 8, NH); MS found

m/e 418, calcd: 418.21 for C22H30N206.

’-I° no. . nu - - -10 o. ‘1 - ’ ‘-uu‘1 - 501.1“ 11' hr.
With stirring, boron trifluoride etherate (5.1 ml) was added dropwise to a mixture
containing dipyrrylmethane 60 (6.27 g, 0.015 mol) and sodium borohydride (1.14 g,
0.030 mol) in dry THF (20 ml) under nitrogen atmosphere. After the addition was
complete, the reaction was stirred for 0.5 h. Acetic acid (2 ml) was added dropwise,
followed by water until hydrogen evolution ceased. The product was extracted into
dichloromethane (30 ml) and washed several times with water. The solvent was removed
under vacuo and the resulting solid was crystallized with methanol/water to give the title
compound (4.76 g, 0.013 mol) in 84% yield. m.p. 79-80 °C; 'H NMR (300 MHz, CDCl,):
81.32, 1.33 (3H each, t, COZCHzflL), 1.86 (1H, t, CHZCHZQH), 2.02, 2.25, 2.29 (3H
each, s, CH3), 2.72 (2H, t, CHZCHZOH), 3.81 (2H, m, CH29H20H), 3.86 (2H, s, CH2),

4.26 (4H, m, COZCHZCH3), 8.60, 9.65 (1H each, S, NH); MS found m/e 376, calcd 376.20

for ConzsNzOs.

 

A 100-ml round-bottomed flask equipped with a reflux condenser was charged with

65

dipyrrylmethane 61 (4.76 g, 0.013 mol), 60 m1 of ethylene glycol, and 5g of sodium
hydroxide. The reaction mixture was refluxed for overnight under nitrogen. Upon
cooling of the solution to room temperature, water was added and the precipitate was
filtered off, washed with water, and dried to afford the pure a-free dipyrrylmethane (2.82
g, 0.012 mol) in 94% yield. 1H NMR (300 MHz, CDCl,): 8 1.70 (1H, br, CHZCHZQH),
1.98, 2.00, 2.02 (3H each, s, CH3), 2.70 (2H, t, CHZCHon), 3.81 (2H, m, CHZCH20H),
3.80 (2H, s, CH2), 6.36, 6.37 (1H each, s, a-H), 7.51, 8.94 (1H each, s, NH); MS found

m/e 232.2, calcd 232.16 for CMHZONZO.

' - .., .... 1- . - ..-. - -. u. . -'uu‘ 19.;01‘: u‘ ....-.

A 250-ml round-bottomed flask equipped with a reflux condenser was charged with
3,4,5-trimethoxybenzylaldyhe (6.66 g, 34.1 mmol), pyrrole 19 (12.33 g, 68.2 mmol), and
130 ml of absolute ethanol. A few drops of concentrated HCl were added, and the stirred
solution was refluxed overnight under nitrogen. At the end of this time, TLC (silica gel,
20% EtOAc/hexane eluent) indicated the absence of the starting material. The solvent
was removed in vacuo, and the red oil was loaded onto a silica gel column. Elution with
20% EtOAc/hexane yielded the title compound as pale yellow oil. Drying under high
vacuum gave the dipyrrylmethane as a pale yellow solid (11.5 g, 21.3 mmol) in 62%
yield. 1H NMR (300 MHz, CDCl3): 8 1.10 (6H, t, CHZCH3), 1.31 (6H, t, COzCHZCH3),
1.79 (6H, s, CH3), 2.72 (4H, q, CHZCH3), 3.75 (6H, s, m-OCHg), 3.85 (3H, s, p-OCH3),
4.24 (4H, q, C02CH2CH3), 5.48 ( 1H, s, CH), 7.25 (2H, aromatic), 8.24 (2H, s, NH) ppm;

MS found m/e 540, calcd 540.28 for C,,H,,N,0,.

66

Dipyrrylmethane 63 was saponified and decarboxylated with sodium hydroxide in
ethylene glycol under conditions described before, affording the pure a—free
dipyrrylmethane (7.83 g, 0.0198 mol) in 92.8%. IH NMR (300 MHz, CDCl3): 8 1.10 (6H,
t, CHZCH3), 1.79 (6H, s, CH3), 2.40 (4H, q, CHZCH3), 3.70 (6H, s, m-OCH3), 3.80 (3H, s,
p-OCH3), 5.38 (1H, s, CH), 6.30 (2H, aromatic), 6.35 (2H, 3, 01-11), 7.34 (2H, s, NH); MS

found m/e 396, calcd 396.24 for C24H32N203.

" ‘-'1 --u11 1--1-1--1u‘ ‘ -u11'1o.‘11-1 11-1.1-1

Formylation of dipyrrylmethane 64 (5.5 g, 0.0139 mol) was effected with POCl3 in DMF
under conditions described previously to give the title compound (5.0 g, 0.0110 mol) in
79.5% yield. m.p. 155-156 °C; 1H NMR (300 MHz, CDCl3): 8 1.18 (6H, t, CHZCH3),
1.82 (6H, s, CH3), 2.70 (4H, q, CHZCH3), 3.70 (6H, s, m-CH3), 3.85 (3H, s, p-CH3), 5.45
(1H, s, CH), 6.28 (2H, aromatic), 8.90 (2H, 5, NH), 9.50 (2H, s, aldehyde); MS m/e 452.4,

calcd 452.23 for C26H32N205.

' .. . ,1, , . . . ° . .
.- . - -. ..o ' -- -'.. ..o‘... - .-. ..Q.‘ . -

A 500-ml round-bottomed flask was charged with 65 (1.356 g, 3.00 mmol), 62 (0.696 g,
3.00 mmol), and 320 ml of THF:MeOH (2:1). The reaction mixture was purged with
nitrogen and covered with foil, Perchloric acid (70%, 1 ml) was added and the solution
was allowed to stir in the dark for 12 hours. At the end of this time, o-chloranil (1.2 g,

4.72 mmol) was added and the mixture was stirred for an additional 12 h. The reaction

67

mixture was poured into brine and extracted several times with methylene chloride. The
organic layers were combined, washed with sodium bicarbonate, water, and dried over
sodium sulfate. The solvent was removed under reduced pressure to give a dark solid.
After chromatography on Silica gel (2% MeOH / CHZCl2 eluent), porphyrin 66 was
isolated (920 mg, 1.43 mmol) in 47.8% yield. m.p. >275 °C; UV-vis: km 404, 501, 536,
569, 622 mm 1H NMR (300 MHz, CDCl,): 8 -3.10 (2H, S, NH), 1.78 (6H, t, CHZCH3),
2.40, 2.42, 3.60, 3.62, 3.66 (3H each, s, CH3), 3.92 (6H, s, m-OCH3), 4.1 (4H, m,
CHZCH3), 4.20 (3H, s, p-OCH3), 4.32 (2H, t, CHZCHZOH), 4.50 (2H, m, CHZCHZOH),
7.32 (2H, s, aromatic), 9.92, 10.16, 10.18 (1H each, S, mesa); MS found m/e 646, calcd

646.35 for c.0H,,N,o..

3 . o ' 9! ' ‘ _ o _ .
" ' I. I I - 0". I ' ‘ ‘IIUI UI.‘II I ' 0". I1" I "'

mmhxrinfl

Benzoyl chloride (5 ml) was added dropwise over 10 minutes to a solution consisting of
porphyrin 66 (798 mg, 1.24 mmol) in DMF ( 30 ml), while maintaining the temperature
below 5 °C. The solution was allowed to stir at this temperature for 20 min and then
heated on a steam bath for 20 min. Aqueous ethanol (50%, 50 ml) containing sodium
carbonate (10 g) was added and the mixture was warmed on the steam bath for 15 min.
Water was added until all sodium carbonate residue had dissolved and the porphyrin
precipitated. The precipitate was collected and recrystallized from CHZCIZ/methanol to
give 67 (728 mg, 1.10 mmol) in 88% yield. m.p. >275 °C; UV-vis: km 404, 502, 536,
569, 624 nm; 1H NMR (300 MHz, CDCl3): 8 -3.24, -3.22 (1H each, s, NH), 1.78 (6H, t,

€11,911», 2.60, 2.62, 3.60, 3.62, 3.64 (3H each, s, CH3), 3.92 (6H, s, m-OCH3), 4.05 (4H,

68

m, CHZCH3), 4.20 (3H, s, p—OCH3), 4.32 (2H, t, flizCHZOH), 4.50 (2H, t, CH2CH2C1),
7.34 (2H, S, aromatic), 9.84, 10.16, 10.19 (1H each, s, mesa); MS found m/e 664, calcd

664.32 for c.0H,,c1N,o,.

9 .'_ 9‘, 3 ' . - 9 - . ' '
.- 1-- -u11 10.1911 - 1-01.-11.1- - I MIN"!

A 250-ml round-bottomed flask equipped with a reflux condenser was charged with
chloroethylporphyrin 67 (665 mg, 1.0 mmol), pyridine (60 ml), and DBU (3.5 ml). The
reaction mixture was refluxed for 30min under nitrogen. Upon cooling of the solution to
room temperature, the reaction mixture was poured into water and extracted several times
with methylene chloride. The organic layers were combined, washed with hydrochloric
acid (5%), saturated sodium bicarbonate solution and water. After drying over sodium
sulfate, the solvent was removed under reduced pressure and the residue was
chromatographed on silica gel (dichloromethane eluent). The porphyrin obtained was
further recrystalization from dichloromethane/methanol to afford the title compound (504
mg, 0.80mmol) in 80% yield; m.p. >275 °C; UV-vis: km 406, 506, 541, 574, 629 nm;
‘H NMR (300 MHz, CDCl3): 8 -3.32, -3.22 (1H each, 8, NH), 1.75 (6H, t, CHZCH3), 2.60,
2.64, 3.60, 3.62, 3.64 (3H each, s, CH3), 3.92 (6H, s, m-OCH3), 4.00 (4H, m, CHZCH3),
4.18 (3H, s, p-OCH3), 6.12 (1H, d, cis-CH=CH2), 6.40 (1H, t, trans- CH=CH2), 7.32 (2H,
s, aromatic), 8.24 (1H, dd, CH=CH2), 10.02, 10.10, 10.20 (1H each, s, mesa); MS found

m/e 628, calcd 628.34 for C40H44N4O3.

. ° 9 9 ' , 9 , , 1
.-.‘. - - -.| ._.. . -- 1-... .Q.‘... _ -

69

nemamzthxhnomhmafl

Osmium tetraoxide (254 mg, 1.0 mmol) was added to the mixture of vinylporphyrin (610
mg, 0.97 mmol), dichloromethane (100 m1) and pyridine (1 ml). The reaction mixture
was stirred for about 30 min until the TLC showed completion of the reaction. Methanol
was added and H2S was bubbled through the mixture for 10 min. The solvent was
removed on steam bath in the hood and the resulting residue chromatographed on silica
gel (4% methanol/dichloromethane eluent) to give the title compound (550 mg, 0.84
mmol) in 88% yield. m.p. >275 °C; UV-vis: 71M 404, 502, 538, 570, 623 nm; lH NMR
(300 MHz, CDCl,): 8 -3.45, 3.25 (1H each, 8, NH), 1.75 (6H, m, CHZQH3), 2.60, 2.64,
3.50 (3H each, s, CH3), 3.60 (6H, s, CH3), 3.92 (6H, s, m-OCH3), 4.02 (4H, m, CHZCH3),
4.20 (3H, S, p—OCH3), 4.58 (2H, m, CH(OH)CHZOH), 6.18 (1H, m, CH(OH)CHZOH),
7.32 (2H, s, aromatic), 10.02, 10.10, 10.18 (1H each, s, mesa); MS found m/e 644 (1W-

H20), calcd 644.33 for C40H44N404

1-0‘1 - -1111 -- "W-I11‘11.111'1 - {-1‘1.q11‘,1 11111111

An aqueous sodium periodate (5%, 20 ml) solution was added to a solution of porphyrin
diol 69 (550 mg, 0.84 mmol) in pyridine (50 ml). The mixture was heated on steam bath
for 0.5 h. Upon cooling , water (50 ml) was added and a precipitate formed. The
precipitate was collected and recrystallized from dichloromethane/methanol to give 70
(510 mg, 0.81 mmol) in 96% yield. m.p. >275 °C; UV-vis: km 417, 519, 560, 584, 640
nm; 1H NMR (300 MHz, CDCl3): 8 -3.22 -2.92 (1H each, s, NH), 1.75 (6H, m, CHZCH3),

2.56, 2.64, 3.60 (3H each, s, CH3), 3.90 (6H, s, CH3), 3.94 (6H, s, m-OCH3), 4.06 (4H, m,

70

932C119, 4.20 (3H, s, p—OCH3), 7.32 (2H, s, aromatic), 10.00, 10.20, 10.70 (1H each, s,

mesa), 11.40 (1H, s, aldehyde); MS found m/e 630, calcd 630.32 for C39H42N4O4.

9 9 9

Jones reagent (CrO3/HZSO4, 5 eq.) was added to a stirred solution of porphyrin aldehyde
70 (126 mg, 0.20 mmol) in acetone (30 ml) at 0 °C. The reaction was monitored by TLC
until the starting porphyrin disappeared. Ice (30 g) was added and the solution was
neutralized with aqueous saturated sodium bicarbonate solution. The mixture was
extracted with dichloromethane three times and the organic layers were combined,
washed with water and dried over sodium sulfate. After evaporation of the solvent, the
residue was chromatographed on a silica gel to give the product (81 mg, 0.12 mmol) in
60% yield. m.p. >275 °C; UV-vis: Am” 411, 512, 551, 580, 632 nm; 1H NMR (300 MHz,
CDCl3): 8 -3.55 -3.20 (1H each, s, NH), 1.80 (6H, m, CHZCH3), 2.56, 2.64, 3.60, 3.62,
3.85 (3H each, s, CH3), 3.92 (6H, 8, m-OCH3), 4.10 (4H, m, CHZCH3), 4.20 (3H, s, p-
OCH3), 7.32 (2H, S, aromatic), 10.00, 10.10, 10.20 (1H each, s, mesa); MS (FAB), m/e

646.4, calcd 646.32 for C39H42N4Os.

' 1 ' 9 9 9 ' _ - 1 . ‘
I u .A.1 ' 9". I ' ' 'I. II II. ‘II I ' 9‘. I-- II ,I -

The insertion of zinc into porphyrin 71 was carried out with Zn(OAc)2 in CHCl3-MeOH
as described previously, yielding 80 mg of porphyrin 72 (90%). m.p. >275 °C; UV-vis:

km 419, 548, 592 nm; MS (FAB), m/e 708.3; calcd 708.23 for C39H40N405Zn.

71

99 9 ' , , o ' 9 - - ’
- - III II.AII I - 1". .I ' - eII-1-II--.II I IIIIIIII

13

A 100-ml round-bottomed flask equipped with a reflux condenser was charged with
porphyrin aldehyde 70 (126 mg, 0.20 mmol), hydroxyamine hydrochloride (100 mg, 1.4
mmol) and 5 ml of 95% formic acid. The reaction mixture was refluxed under nitrogen
overnight. Upon cooling of the solution to room temperature, the reaction mixture was
poured into water. It was neutralized with aqueous saturated sodium bicarbonate solution
before extracted several times with methylene chloride. The organic layers were
combined and washed with water twice. After dried over sodium sulfate, the solvent
was removed on a rotary evaporator and the resulting solid was chromatographed on
silica gel (dichloromethane eluent) to give the title compound ( 119 mg, 0.19 mmol) in
95% yield. m.p. >275 °C; UV-vis: Am 410, 514, 552, 557, 629 nm; 1H NMR (300 MHz,
CDCl3): 8 -3.50, -3.20 (1H each, 8, NH), 1.75 (6H, m, CHZCH3), 2.56, 2.70, 3.62, 3.64,
3.85 (3H each, s, CH3), 3.90 (6H, S, m-OCH3), 4.10 (4H, m, CHZCH3), 4.20 (3H, s, p-
OCH3), 7.30 (2H, s, aromatic), 10.00, 10.08, 10.20 (1H each, S, meso); MS found m/e

627.3, calcd 627.32 for C39H4,N,O3.

K. 1' ' eII” ,, nIIII'IIclII'I ' I'I’I - I-I‘I.-,II',I -
mmhxrinld

Nickel acetate was added to a solution of porphyrin nitrile free base (119 mg, 0.19 mmol)
in DMF (15 ml) and the mixture refluxed until chelation was complete (monitored by

both UV-vis and TLC, ca. 1 hours). Water was added and the solution was extracted

72

with dichloromathane. The organic layer was washed several times with water. After
removal of solvent, the solid residue was chromatographed on silica (eluted with
dichloromethane) to give 74 (120 mg, 0.17mmol) in 92% yield. m.p. >275 °C; UV-vis
Am 406, 532, 574; 1H NMR(300 MHz, CDCl3): 8 1.62 (6H, m, CHZCH3), 2.42 (6H, s,
CH3), 3.40 (6H, s, CH3), 3.70 (3H, s, CH3), 3.88 (4H, m, CHZCH3), 3.90 (6H, s, m-OCH3),
4.14 (3H, s, p-OCH3), 7.10 (2H, s, aromatic), 9.56 (1H, s, meso), 9.64 ( 1H, s, meso), 9.66

(1H, s, meso); MS found m/e 683, calcd 683.24 for C39H39NSO3Ni.

. ‘_ -11"'1,1..11- _ ,, ’11'11-11.111-1 _ :1'51 _ _
l l l . l l . 1 15
Porphyrin nitrile 74 (120 mg, 0.17 mmol) and dry toluene (20 ml) were placed in a
Schlenck tube. After the system was purged with argon three times,
chloromethylaluminum(III) amide (1 M, 1 ml) was introduced by syringe. The reaction
mixture was stirred at 80 °C for 3 days under an argon atmosphere. Then the reaction
mixture was added to mixture of silica (5 g) and chloroform (20 ml). After stirring for
0.5 h, the mixture was filtered and washed with dichloromethane. The solid mixture was
loaded on a silica gel pad and eluted with 15% methanol in dichloromethane to give the
title compound (116 mg, 0.16 mmol) in 93% yield. m.p. >275 °C; UV-vis: Am 406, 530,
574 nm; 1H NMR (300 MHz, CDCl,): 8 1.54 (3H, t, CHZCH3), 1.62(3H, t, CHZCH3), 2.40,
2.44, 3.05, 3.08, 3.48 (3H each, s, CH3), 3.56 (2H, q, CHZCH3), 3.75 (2H, q, CHZCH3),
3.90 (6H, s, m—OCH3), 4.12 (3H, s, p-OCH3), 6.82 (2H, br, axial NH of amidinium), 7.10
(2H, s, aromatic), 9.24 (2H, S, mesa), 9.60 (1H, s, mesa), 10.88 (2H, s, equatorial NH of

amidinium). MS (FAB), m/e (MH+) 701.2, calcd 701.28 for C39H42N603.

73

o o o I , A, , o . . . o- . - .
I ' II I I II' " 'I. II .I‘. ‘II I ' 9'. I " 0". I... II I '

mmhuinJl

Concentrated sulfuric acid (2 ml) was added to a solution of the nickel complex 75 (50
mg, 0.068 mmol) in dichloromethane (10 ml). The mixture was stirred until all the
porphyrin was extracted into the sulfuric acid layer. Ice (20 g) was added, followed by
saturated aqueous sodium bicarbonate. After neutralization, the organic layer was
collected, washed with water and dried over sodium sulfate. The solvent was removed
under reduced pressure to give the free base 76. m.p. >275 °C; UV-vis: 98m: 407, 510,
547, 574, 626 nm.

To the above free base, zinc chloride (40 mg) and DMF (15 ml) was added. The mixture
was heated until chelation was complete (monitored by both UV-vis and TLC, ca. 10min).
After cooling to the room temperature, water was added to the mixture and it was
extracted with dichloromethane. The organic layers were washed with water several
times. After removal of the solvent, the solid residue was chromatographed on silica gel
(eluted with 15% methanol in dichloromethane) to give77 (44 mg, 0.060mmol) in 88%
yield. m.p. >275 °C; UV-vis: km: 414, 546, 589 nm; MS (FAB), m/e 707.2 (MH+), calcd

706.27 for C39H42N6O3Zn.

Chapter III

Characterization of Amidinium-Carboxylate Salt Bridge

This Chapter describes the characterization of the amidinium-carboxylate salt
bridge formed by porphyrin amidinium and benzoate utilizing X-ray crystallography.
The binding strength of this salt bridge formed by various porphyrins and aromatics has
been measured by 1H NMR and UV-vis spectroscopies. ET rates measured by using

fluorescence quenching technique are also presented.

1. Crystal Structure

The complex formed by porphyrin amidinium 75 and benzoate consists of two
crystallographically independent molecular complexes. Their structures are shown by the
ORTEP drawing in Figure 8 and Figure 9, respectively. Crystal data and refinement
parameters are given in Table 1. The data for selected bond distances and angles for both
structures are given in Table 2. Table 3 lists atomic coordinates of all atoms.

Both structures show that an amidinium-carboxylate salt bridge is formed

between porphyrin amidinium 75 and benzoate. In one structure (Figure 8), two internal

74

75

protons (HNSa and HN6a) of the amidinium group form the hydrogen bond with oxygen
atoms (O4 and OS) of carboxylate and O"'H distances are 1.800(5) and 1.874(5) A,
respectively. The bond angles for N6-C34-N5 and O4-C40-OS are 118.0(7) and
121.9(7)°, respectively. The two N-O distances are 2.81 and 2.76 A. These relatively
short hydrogen bond distances indicate significant stability of the salt bridge and
relatively strong hydrogen bonding. The amidinium group rotates by 42° with respect to
the plane of the porphyrin ring (defined by the four pyrrole nitrogen atoms) due to the
steric interaction of the mesa-proton. The salt bridge twists by 5.4° (dihedral angle
defined by the planes of the CN2 and CO2 atoms of the salt bridge). The four Ni-N bond
lengths in porphyrin 75 [1.927(6), 1.924(6), 1.928(6), 1.900(6)] are typically short,
resulting in a deformation of the macrocycle ring of 75 from planarity. The normal
radius of the cavity in an undistorted metalloporphyrin has been estimated to be 2.01 A,58
whereas the usual Ni-N bond length found in diamagnetic nickel(II) square-planar
complexes is ca. 1.85 A.59 Hence, the porphinato-core must contract from the ideal
situation to accommodate a low-spin nickel(II) atom. It has been postulated”60 that 1.96
A is the smallest radius the porphyrin cavity may have in order to maintain a planar
structure and this is supported by experimental results. For example, in nickel(II) 2,4-
diacetyldeuteroporphyrin-IX dimethyl ester,‘51 the Ni-N distance is 1.960(8) and this
compound is essentially planar. In the nicke1(II) OEP,62 the Ni-N distance is 1.929(3) and
the porphyrin ring has severe warping.

The overall structural features of the salt bridge in the other independent structure
are similar (Figure 9). The O"'H bond distances are 1.854(6) and 1.838(6) A. The N-O

distances are 2.78 and 2.79 A. The amidinium group of this structure rotates 61 .8° out of

76

 

ass (3038
’ »
C15 I C37
C13 ’) C14 z; C16 017
- - In -
035 " ., ‘ x. 18
C12 /' ‘
I - 1‘
N1
(\
C45 C46 04' .
C41 ‘
© 03°
032
C44 C42
C43

 

Figure 8. Top and side views of the ORTEP diagrams of the crystal structure of the Salt-

bridged supramolecular assembly formed by association of 75 with benzoate (structure 1)

77

 

Figure 9. Top and Side views of the ORTEP diagrams of the crystal structure of the salt-
bridged supramolecular assembly formed by association of 75 with benzoate (structure 2)

78

Table 1. Crystal Data and Conditions for Crystallographic Data Collection

 

and Structure Refinement
Formula Ni 0, N6 C4,5 H48
Forrnular weight 822.11
Diffractometer used Nonius
Space Group Triclinic P_1
a (A) 15.497(3)
b (A) 16.268(3)
c (A) 19.483(7)
01 (°) 113.589(23)
[3 (°) 109.687(22)
7 (°) 93.435(14)
V (A3) 4128.8(18)
Z 4
Dcalc. (g ' cm‘3) 1.323
A (A) 0.7107
F(000) 1732.
Unit cell detn: #;(20 range).) 25;( 19.00 - 24.24 °)
Scan type 0/20
Scan width (degree) 2(0.80+0.35tan(0))
Scan Speed (degree/min) 3.30-8.24
(20)max 45.0
h k 1 ranges (-16; 16) (0; 17) (-20; 19)
11 (cm“) 5.219
Crystal size (mm) 0.05 X 0.50 x 1.50
Transmission 0.795; 1.000
Temperature (K) 298
# of meas. reflns. 10777
# of obsed relfns. (I>2.0o(I)) 5300
# of unique reflns. 10761
Rf; Rw 0.065; 0.058
GoF 2.06
Refinement program NRCVAX
# of atoms 212

# of refined params..)
Minimize function
Weights scheme

The weight modifier K in KFo2 is

(8/ 0),”.
Residual in final D-map (e/ A 3)

1045 ( 5300 out OH 0761 reflns
Sum(w|Fo-Fc|2)

1/[62(FO)]

0.000100

0.0087

-0.400; 0.630

 

NOTE :
Rf = 2(Fo-Fc)/ 2(Fo)

Rw = [2(w(Fo-Fc)2)/ 2(wF02)]"2

GoF = [2(w(Fo-Fc)2)/(No. of reflns - No. of params.)]"2

79

Table 2. Selected Bond Distances and Bond Angles and Their Estimated
Standard Deviations for Porphyrin Amidinium Benzoate

 

 

 

 

 

Structure 1 Structure 2

Bond Distance (A)
Ni-Nl 1.927(6) Ni'-N1' 1.925(7)
Ni-N2 1 .924(6) Ni'-N2' 1 .942(7)
Ni-N3 1 928(6) Ni'-N3' 1 .915(7)
Ni-N4 1 .900(6) Ni'-N4' 1 .931(7)
N5-C34 1.301(10) N5'-C34' 1.311(11)
N5-Hn5a 0.938(6) N5'-Hn5'a 0.923(7)
N5-Hn5b 0.980(6) N5'-Hn5'b 0.986(7)
N6-C34 1.349(10) N6'-C34' 1.328(11)
N6-Hn6a 0.957(6) N6'-Hn6'a 0.934(7)
N6-Hn6b 0.942(7) N6'-Hn6'b 0.983(7)
C40-C41 1.475(12) C40'-C41' 1.487(12)
C40-O4 1.264(10) C40'-O4' 1.261(10)
C40-OS 1 27000) C40'-OS' 1.254(10)
O4-Hn5a 1 .874(5) O4'-Hn5'a 1 .83 8(6)
OS-Hn6a 1 .800(5) 05'-Hn6'a 1 854(6)

Bond Angle (deg)

C34—N5-Hn5a 125.3(7) C34'-N5'-Hn5'a 1 17.7(7)
C34-N5-Hn5b l 17.7(7) C34'-N5'-Hn5'b 120.3(7)
C34-N6-Hn6a 1 18.3(7) C34'-N6'-Hn6'a l 16.2(7)
C34-N6-Hn6b 101 .4(6) C34'-N6'-Hn6'b 122. 1(7)
Hn5a-N5-Hn5b 1 16.9(6) Hn5'a-N5'-Hn5'b 122.1(7)
Hn6a-N6-Hn6b 128.3(7) Hn6'a-N6'-Hn6'b 121 .6(7)
N5-C34-N6 118.0(7) N5'-C34'-N6' 118.8(8)
N5-C34—C8 120.5(7) N5'-C34'-C8' 120.0(8)
N6-C34-C8 121.5(7) N6'-C34'-C8' 121.2(7)
C41-C40-O4 1 19.7(7) C41 '-C40'-O4' l 17.3(8)
C41 -C40-05 1 1 8.4(7) C41 '-C40'-OS' 1 18.5(7)
O4-C40-OS 121 .9(7) O4'-C40'-OS' 124.2(8)
C40-C41-C46 120.0(8) C40'-C41'-C46' 121.5(8)
C40-O4-Hn5a 1 15.9(5) C40'—O4'-Hn5'a 1 19.5(6)
C40-OS-Hn6a 124.8(5) C40’-OS'-Hn6'a 1 l 1.2(5)
N5-Hn5a-O4 176.0(5) N5'-Hn5'a-O4' 175.2(6)
N6-Hn6a-OS 177.5(4) N6'-Hn6'a-OS' 165.6(6)

 

80

Table 3. Atomic Parameters x,y,z and Beq.

 

 

x y z Beq
Ni 0.49612( 8) 0.11872( 8) 0.39834( 6) 2.98( 7)
N1 0.4896 ( 4) 0.1182 ( 5) 0.2976 ( 4) 3.4 ( 5)
N2 0.6305 (4) 0.1333 ( 4) 0.4361 ( 3) 2.6 ( 4)
N3 0.5035 ( 4) 0.1218(5) 0.5001 ( 4) 3.2 ( 5)
N4 0.3632 ( 4) 0.1023 ( 5) . 0.3605 ( 3) 2.9 ( 4)
N5 0.9165 ( 5) 0.0620 ( 5) 0.5291 ( 4) 4.2 ( 5)
N6 0.8870 ( 5) 0.1539 ( 5) 0.6382 ( 4) 4.1 ( 5)
C1 0.4114 ( 6) 0.0844 ( 7) 0.2233 ( 5) 4.2 ( 6)
C2 0.4407 ( 7) 0.0956 ( 9) 0.1643 ( 5) 6.9 (9)
C3 0.5314 ( 7) 0.1397 ( 8) 0.2030 ( 6) 6.3 ( 8)
C4 0.5644 ( 6) 0.1503 (6) 0.2858 ( 5) 4.1 ( 6)
C5 0.6562 ( 6) 0.1718 ( 6) 0.3363 ( 5) 3.8 ( 6)
C6 0.6880 ( 6) 0.1571 ( 6) 0.4023 ( 5) 3.2 ( 6)
C7 0.7827 ( 5) 0.1549 ( 5) 0.4445 ( 4) 2.8 ( 5)
C8 0.7835 ( 5) 0.1298 ( 6) 0.5019 ( 4) 3.0 ( 5)
C9 0.6895 ( 5) 0.1189 ( 5) 0.4981 ( 4) 2.5 ( 5)
C10 0.6636 ( 6) 0.1053 ( 6) 0.5548 ( 5) 2.9 ( 5)
C11 0.5761 ( 6) 0.1130(6) 0.5574(4) 2.9 ( 5)
C12 0.5531 ( 6) 0.1239(6) 0.6279(5) 3.4 ( 6)
C13 0.4672 ( 6) 0.1376 ( 6) 0.6094 ( 5) 4.0 ( 6)
C14 0.4335(6) 0.1355(6) 0.5296(5) 3.6 ( 6)
C15 0.3450 ( 6) 0.1350 ( 7) 0.4877 ( 5) 4.2 ( 6)
C16 0.3105(6) 0.1132(6) 0.4062(5) 3.7(6)
C17 0.2123 ( 6) 0.0855 ( 6) 0.3564 ( 5) 4.3 ( 7)
C18 0.2025 ( 6) 0.0537 ( 6) 0.2774 ( 5) 3.9 ( 6)
C19 0.2972 ( 6) 0.0691 ( 6) 0.2806 ( 5) 3.5 ( 6)
C20 0.3222 ( 6) 0.0545 ( 6) 0.2146 ( 5) 3.8 ( 6)
C21 0.2455 ( 6) 0.0069 ( 6) 0.1285 ( 5) 4.1 ( 6)
C22 0.2011 ( 6) 0.0546 ( 6) 0.0915 ( 5) 3.9 ( 6)
C23 0.1332 ( 6) 0.0084 ( 6) 0.0117 ( 5) 3.7 ( 6)
C24 0.1136 ( 6) 0.0869 ( 6) -0.0250 ( 5) 3 ( 6)

 

Table 3 (cont’d)

81

 

C25
C26
C27
C28
C29
C30
C31
C32
C33
C34
C35
C36
C37
C38
C39
C40
C41
C42
C43
C44
C45
C46
01
02
O3
O4
05
Ni'
N1'
N2'
N3'
N4'
N5'

0.1535 ( 7)
0.2253 ( 7)
0.1017 ( 7)
0.0788 ( 9)
0.1271 (8)
0.3858 ( 8)
0.5931 (8)
0.6343 (13)
0.8625 ( 6)
0.8640 ( 6)
0.6196 ( 6)
0.4109 ( 7)
0.1342 ( 6)
0.1023 ( 8)
0.1083 ( 7)
1.1051 ( 6)
1.1957 ( 6)
1.2678 ( 6)
1.3546 ( 7)
1.3690 ( 7)
1.2976 ( 8)
1.2114 ( 7)
0.0850 ( 4)
0.0430 ( 5)
0.1272 ( 6)
1.0834 ( 4)
1.0513 ( 4)

-0.42867( 9)

-05304 ( 5)
-0.3359 ( 5)
-0.3282 ( 5)
-05190 ( 5)
-0.0662 ( 5)

-0.1355 ( 7)
-0.0879 ( 7)
0.1450 ( 7)

-O.1528 (10)

—0.2790 ( 7)
0.0642 (14)
0.1911 ( 8)
0.1246 (11)
0.1797 ( 7)
0.1143 ( 6)
0.1219 ( 6)
0.1557 ( 8)
0.0892 ( 7)
0.1771 (9)
0.0140 ( 8)
0.0832 ( 6)
0.0833 ( 6)
0.0597 ( 6)
0.0646 ( 7)
0.0952 ( 8)
0.1172 ( 8)
0.1136 ( 7)
0.0480 ( 4)
-01340 ( 5)
-02305 ( 5)
0.0390 ( 4)
0.1289 ( 4)
0.62335( 8)
0.6045 ( 5)
0.6314 ( 5)
0.6434 ( 5)
0.6123 ( 5)
0.5682 ( 5)

0.0137 ( 5)
0.0939 ( 5)
0.0019 ( 6)
-O.l647 ( 7)
0.0166 ( 7)
0.0741 (7)
0.1721 ( 7)
0.1379 ( 9)
0.4241 (5)
0.5571 ( 5)
0.7028 ( 5)
0.6615 ( 6)
0.3869 ( 5)
0.4006 ( 7)
0.2059 ( 6)
0.7042 ( 5)
0.7620 ( 5)
0.7381 ( 5)
0.7944 ( 6)
0.8754 ( 6)
0.8974 ( 6)
0.8438 ( 5)
-00329 ( 3)
-0.1046 ( 3)
-0.0277 ( 4)
0.6284 ( 3)
0.7326 ( 3)

-O.16357( 7)

-01320 ( 4)
-0.0635 ( 4)
-01954 ( 4)
-0.2652 ( 4)
0.0393 ( 4)

58(7)
51(7)
58(8)
101(1n
81(9)
151(rn
9500)
148(MD
45(6)
36(6)
44(7)
71(9)
51(7)
83(1D
69(9)
41(6)
36(6)
43(6)
61(8)
69(8)
71(9)
61(8)
50(4)
65(5)
87(6)
44(4)
50(4)
32x7)
42(5)
38(5)
31(4)
38(5)
61(5)

 

Table 3 (cont’d)

82

 

N6' -00491 ( 5) 0.6991 ( 6) 0.1506(4) 6.8 ( 6)
c1' -0.6259 ( 6) 0.5786 ( 6) -0.1767 ( 5) 4.5 ( 6)
02' -0.6762 ( 6) 0.5846 ( 7) -01242 ( 5) 5.0 ( 7)
(23' -0.6108 ( 7) 0.6110 ( 7) -00495 ( 5) 5.7 ( 7)
(34' -0.5206 ( 6) 0.6240 ( 6) -0.0526 ( 5) 4.3 ( 7)
CS' -0.4369 ( 6) 0.6405 ( 7) 0.0097 ( 5) 4.8 ( 7)
C6' -03510 ( 6) 0.6422 ( 6) 0.0066 ( 5) 4.2 ( 6)
C7' -O.2657 ( 6) 0.6459 ( 6) 0.0679 ( 5) 4.6 ( 6)
C8' -0.1984 ( 6) 0.6355 ( 6) 0.0363 ( 5) 4.4 ( 6)
(39' -0.2443 ( 6) 0.6270 ( 6) -00450 ( 5) 3.8 ( 6)
c10' -0.1969 ( 6) 0.6231 ( 6) -0.0960 ( 5) 4.5 ( 6)
C11' -0.2370 ( 6) 0.6341 ( 6) -0.1655 ( 5) 4.3 ( 6)
c12' -0.1863 ( 6) 0.6477 ( 6) -02105 ( 5) 4.7 ( 6)
C13' -0.2426 ( 6) 0.6737 ( 6) —0.2637 ( 5) 4.7 ( 6)
GM -03327 ( 6) 0.6673 ( 6) -0.2557 ( 5) 3.8 ( 6)
as -O.4128 ( 7) 0.6715 ( 6) -0.3100 ( 5) 4.7 ( 7)
C16' -0.5005 ( 6) 0.6392 ( 6) -0.3177 ( 5) 4.0 ( 6)
C17' -O.5847 ( 7) 0.6125 ( 7) -0.3891 ( 5) 4.7 ( 7)
C18' -0.6530 ( 7) 0.5660 ( 7) -0.3824 ( 5) 5.1 ( 7)
019' -0.6145 ( 6) 0.5715 ( 6) -0.3009 ( 5) 4.0 ( 6)
020' -0.6658 ( 6) 0.5542 ( 6) -0.2614 ( 5) 4.2 ( 6)
av -0.769O ( 6) 0.5110 ( 6) -03053 ( 5) 4.1 ( 6)
022' -0.8337 ( 7) 0.5611 ( 7) -03204 ( 6) 5.8 ( 7)
C23' -0.9289 ( 7) 0.5192 ( 7) -O.3601 ( 6) 5.3 ( 7)
c24' -O.9564 ( 6) 0.4269 ( 7) -0.3830 ( 5) 5.4 ( 8)
c25' -0.8916 ( 6) 0.3761 ( 6) -0.3692 ( 5) 4.7 ( 6)
C26' -0.7953 ( 6) 0.4174 ( 6) -0.3303 ( 5) 4.7 ( 7)
027' -0.9890 (10) 0.6290 ( 9) -0.3963 ( 8) 9.9 (12)
C28’ -1.1007 ( 8) 0.3877 ( 8) -0.3772 ( 7) 9.1 (10)
(229' -0.8596 ( 8) 0.2287 ( 7) -O.3866 ( 6) 7.9 ( 9)
C30' 077% ( 7) 0.5671 ( 8) -01441 ( 6) 6.6 ( 8)
(231' -0.6237 ( 8) 0.6316 ( 9) 0.0281 ( 6) 8.1 ( 9)
C32' -O.609O ( 9) 0.7330 ( 9) 0.0798 ( 7) 11.1 (11)
C33' —0.2601 ( 7) 0.6592 ( 7) 0.1510(6) 5.9 ( 8)

 

Table 3 (cont’d)

83

 

C34'
C35'
C36'
C37'
C38'
C39'
C40'
C41'
C42'
C43'
C44'
C45'
C46'
01'
02'
O3'
O4'
05'
HNSa
HNSb

HN6a
1-IN6b

-01025 ( 6)
-0.0880 ( 7)
-02214 ( 8)
-05923 ( 9)

-0.5834 (19)

0.7495 (8)
0.1674 ( 6)
0.2655 ( 6)
0.3191 ( 7)
0.4101 ( 7)
0.4508 ( 7)
0.3993 (8)
0.3077 ( 7)
-0.9995 ( 5)
-1.0509 ( 4)
-09245 ( 5)
0.1253 ( 4)
0.1311 ( 4)
0.971

0.898

0.944
0.864

0.6344 ( 7)
0.6366 ( 8)
0.7006 ( 8)
0.6300 ( 7)
0.5494 (14)
0.5159 (10)
0.6368 ( 6)
0.6301 ( 6)
0.5984 ( 6)
0.5942 ( 7)
0.6179 ( 8)
0.6528 ( 8)
0.6578 ( 7)
0.5614 ( 6)
0.3828 ( 5)
0.2838 ( 4)
0.5883 ( 4)
0.6885 ( 5)
0.051

0.031

0.146
0.208

0.0761 ( 5)
-0.1963 ( 6)
-0.3218 ( 6)
-0.4611 ( 6)

-0.5269 (11)

0.4497 ( 6)
0.1889 ( 5)
0.2279 ( 5)
0.1819 ( 5)
0.2187 ( 6)
0.2998 ( 7)
0.3476 ( 6)
0.3106 ( 5)
-0.3783 ( 5)
-04250 ( 4)
-0.3967 ( 4)
0.1130 ( 3)
0.2332 (3)
0.561

0.47

0.672
0.646

52(7)
70(8)
74(9)
74(9)
23.3 (28)
95(10
44(6)
39(6)
50(7)
69(8)
74(9)
73(8)
56(7)
91(7)
76(6)
70(5)
61(4)
67(5)
4

4

4.3
4.3

 

Beq is the Mean of the Principal Axes of the Thermal Ellips

84

the porphyrin plane accompanied by a more twisted salt bridge interface (259° between
the CN2 and the carboxylate planes). We believe that such variabilities in the solid state
accentuate the high degree of rotational freedom of the salt bridge, which is also

anticipated to occur in solution.

11. Determination of Association Constants

A. Pratan NMR

In the course of determining the association constant of the amidinium-
carboxylate salt bridge, we observed that the resonance of NH2 protons of the amidinium
group became broad when the carboxylate was added and eventually collapsed into the
base line. This hindered the accurate determination of the chemical Shift of the proton
involved in the formation of salt bridge. It is believed that the broadening of NH peak is
caused by the coupling of 1“N nucleus, which has a spin number I of 1. The coupling
between the proton and nitrogen are determined by exchange rate of the proton on the
nitrogen atom and the electrical quadrupole moment of the 1‘N nucleus. If the exchange
is rapid, the NH proton(s) is decoupled from the nitrogen atom and the NH peak is
therefore a sharp singlet. Such is the case for the unbound amidinium group. If the NH
exchange rate is slow, the NH peak becomes broad because the quadrupole moment of
the nitrogen nucleus induces a moderately longer lifetime for the spin state of the
nitrogen. The proton thus sees three spin states of the nitrogen nucleus (1 = 1) which are
changing at a moderate rate and the proton responds by giving a broad peak. This is what
we observed for the bound amidinium, in which the formation of hydrogen bond locks

the protons within the interface and slows the exchange of NH protons.

85

Acid is known to accelerate the proton exchange rate and has been introduced in
our titration experiments to improve the resolution of NH peaks. The conjugated acid of
the carboxylate was selected in order to avoid bringing other counter-ions. The binding
studies were carried out in DMSO-d6. With the present of acid, the resolution of the
protons of NH was found to be enhanced dramatically. Figure 10 shows the 1H NMR
Spectral changes resulting from the association of porphyrin 75 to benzoate in DMSO-d6.
Without the addition of benzoate, protons of amidinimn group of porphyrin amidinium
75 displayed two sharp peaks at 9.77 and 9.98 ppm. The addition of benzoic acid did not
have effect on the chemical shifts of the NH protons. Nevertheless, when
tetrabutylammonium benzoate was added, the peak at 9.77 ppm was found Shift down
field (> 4 ppm). This shift was believed due to the formation of hydrogen bonds with
carboxylate and consequently, this peak was assigned as the internal NH protons of the
amidinium group. The peak at 9.98 ppm Shifted up field slightly (< 0.5 ppm) and it was
assigned as the external NH protons of amidinium group. The chemical shift of the
mesa-proton remained unchanged during the titration, which clearly excluded the
possibility that the interaction between the porphyrin and benzoate was due to 11-71
stacking.63

Similar changes were observed when porphyrin amidinium 75, porphyrin phenyl
amidinium 43 were titrated with 3,5-dinitrobenzoate (3,5-DNB) or benzoate. In all
spectra, internal NH protons of the amidinium group shifted downfield upon the
formation the hydrogen bond, while the external NH proton of amidinium group only
changed slightly. In all cases, no rt-n interaction was observed. To obtain the association

constant, the chemical shift of the internal proton of the amidimium group was plotted

86

against the concentration of benzoate to give corresponding titration curves. A typical
titration curve is shown in Figure 11. The association constant was then fitted by using
the non-linear least square method described by Wilcox.68 Table 4 lists association
constants of the salt bridge in DMSO-d6 determined by NMR titration.

We observed that porphyrin effect had little influence on the binding constants of
the same carboxylate. However, it was found when benzoate was replaced by 3,5-
dinitrobenzoate (DNB), the association constant decreased dramatically due to the
electron-withdrawing effect of the nitro groups.

Wilcox‘54 observed that meta and para-substituents on N-octyl-N’-arylthiourea had
large effects on binding when hydrogen bonds were formed with sulfonate. The binding
strength increased when electron-withdrawing groups were presented on the proton donor.
In their case, the N-H bonds become more positive due to the electron withdrawing group
and NH proton become more acidic, which causes the increase of binding strength.
Obviously, Our results showed another aspect of the substituents effects and
complemented the earlier results.

In order to investigate the stoichiometry of the complex formed by amidinium-
carboxylate salt bridge, Job’s method of continuous variation“ was applied. In this
method, solutions containing various concentration ratios of porphyrin amidinium and
carboxylate were prepared in such a manner as to keep the total concentration of the
samples constant. This dictated that a 1:1 complex would reach a maximum value when
the concentration of amidinium was equal to benzoate, while the concentration of a 2:1
complex would reach a maximum value when the concentration of amidinium was twice

that of benzoate. In our study, the chemical shift of the internal amidinitun proton was

87

recorded at each ratio. The concentration of the complex was represented by the product
of the chemical shift changes (relative to unbound amidinium) and the mole fiaction of
anridinium according to the approach of Newcomb.66 Plotting of the concentration vs. the
mole fi'action of amidinium, resulted in a Job’s plot. This plot, as shown in Figure 12,
revealed that the relative amidinium-carboxylate complex concentration approached a
maximum when the mole fraction of amidinium was approximately 0.5. This confirmed
the formation of 1:1 complex between amidinium-carboxylate in solution, which agreed
with the stoichiometry in solid state that was observed in the crystal structure.

In less polar solvents such as dichloromethane and chloroform, the association
constant was found to greatly increase. A difficulty encountered in the determination of
association constants was that unreliable results were obtained by NMR titration.
Wilcox68 has indicated that the optimal concentration for determination association
constants should be 1/Ka. The concentration limit for 1H NMR is greater than ca.10" M
and thus this method is restricted to measure association constant below 105 M". Thus,

UV-vis spectrOSCOpy was applied to determine the association constants.
B. U V-vis

The conjugation between porphyrin and amidinium in porphyrin arrridinium 75
allowed a quantitative assessment of the strength of the amidinium-carboxylate hydrogen
bond by using UV-vis spectroscopy. Specifically, similar to the 1H NMR titration,
addition of increasing quantities of benzoate into a solution of porphyrin amidinium 75 in
dicholorrnethane produced noticeable change in the porphyrin absorption spectrum
(Figure 13). The absorption increased at 403 and 570 nm and decreased at 406 and 574

nm. The set of absorption spectra contained isosbestic points at 408 and 571 nm. The

88

 

lNHin NHex

 

 

 

 

 

 

 

 

 

 

 

 

ppm

Figure 10. Selected 1H NMR spectra of 75 (2.06 mM) with 1 eq. of benzoic acid in the
absence of and in the presence of 1.78, 3.56, 5.35, 7.13, 8.92, 10.70, and 12.48 mM
(bottom to top) of tetrabutylammonium benzoate in DMSO-d6 at room temperature. The
spectral range captures the arrridinium protons internal (N Hi”) and external (N Hex) to the
salt bridge interface and the three mesa protons of the porphyrin ring.

8 ppm

89

 

13.50

13.00

12.50

12.00

11.50

11.00

10.50

10.00

 

 

 

 

950 r r r r r r
0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40

[Carboxylate] x 10'2 (M)

Figure 11. Plot of the chemical Shift of internal protons of the amidinium

versus the concentration of tetrabutylammonium benzoate.

90

 

1.4

1.2

1.0

0.8

XA8

0.6 ’

0.4 ,

0.2 I

 

 

 

0.0
0 0.2 0.4 0.6 0.8 1

Figure 12. Job plot of the supramolecular complex formed by 75 and benzoate. The
total concentration was kept at 3.5 mM and the systems were monitored by 1H NMR

(using the internal proton of anridinium) in DMSO at room temperature.

91

Table 4. Association Constants (KI) and Energies (AGO) of Amidinium-Carboxylate Salt
Bridge in DMSO Determined by NMR Titration. Association Energies are determined
by AG0 = -RTan,

 

 

Anridinium Carboxylate K, AG0
(M'l) (kcal)
75 benzoate 1550 :1: 87 4.37
75 3, S-DNB 250 :t -3.29
53 benzoate 1750 :t 95 -4.45
53 3, S-DNB 134 i 7 -2.90

53 49 1800 i 170 -4.46

 

92

 

2.00 ' 1

*—

1.50 "

Abs.

1.00 '

 

0.50 *'

 

 

 

 

0.00 ‘
350 400 450 500 550 600 650

Figure 13. Selected UV-vis spectra of 75 (5.50 uM) in the presence of 0.0, 1.36, 2.71,
4.07, 5.42, 6.78 and 9.48 uM (increase with arrows) of tetrabutylammonium benzoate in

dichloromethane.

93

 

0.16 -

0.12 —

0.08 -

0.04 -

 

 

 

0.00 ' ' '
0.00 0.50 1.50 2.00 2.50

[Benzoate] x 10‘5 (M)

Figure 14. Plot of the absorption change of 75 at 398 nm versus the concentration of

tetrabutylammonium benzoate

94

binding isotherm was determined by plotting the absorption change at 398 nm against the
concentration of carboxylate (Figure 14). From the plot, the association constant was
determined using the method described previously.

Table 5 lists the association constants measured under various conditions by UV-
vis spectroscopic method. To compare this methodology with NMR, we studied the salt
bridge formed by the same complex in DMSO. Initially, the titration was performed
without the presence of an acid and the association constant was found to be 1.1(1) X 10‘,
which was much higher than that obtained from the NMR titration. At this point, we
decided to measure the association constant under comparable conditions to the NMR
titration. Consequently, with 1 eq. of benzoic acid present, the association constant was
found to be 3.2(3) X 103 M". The result was consistent with that determined by NMR [K,
= 1.55(9) X 103 M"]. Obviously, the presence of benzoic acid decreased the observed
porphyrin carboxylate binding, presumably due to the competitive binding from the acid.

The significant increase of association constants in dichloromethane compared
with that in DMSO Shows a strong solvent effect on the stability of salt bridge. The
change of solvent causes 3.7 kcal change in association energy. This is believed due to
the different dielectric constants of these two solvents. The association energy of
hydrogen bond is generally determined by the overlap of orbitals, salvation energy and
Coulombic interaction.67 In salt bridge, the primary interaction within salt bridge is

Coulombic interaction, which is expressed by equation 3.1:

E =fl (3.1)
8"

where E is Coulombic energy, q+ and q_ are the positive charges associated with the

hydrogen bond, 8 is dielectric constant of solvent and r is the distance between the

 

95

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96

positive and negative charge. The dielectric constant of DMSO is 47.24, while that for
CH2C12 is 8.93. For the same salt bridge, charges are the same and the bond distance
shouldn't vary too much in these two solvents. Consequently, the Coulombic interaction
in DMSO is weakened because of the large 8 and the total hydrogen bond energy of the
salt bridge is lower compare to that in CHZCIZ.

The UV-vis titration method is limited to porphyrin amidinium 75, in which the
amidinium group is electronically coupled to the porphyrin. For porphyrin phenyl 43, in
which the amidinium group is decoupled from the porphyrin, no spectral change can be
detected upon the formation of salt bridge. Hence, its association constant in
dichloromethane can only be referred from that obtained in DMSO. We have
demonstrated previously by NMR titration that porphyrin amidinium 43 has similar
binding properties as those of porphyrin amidinium 75 in DMSO. Therefore, it is
reasonable to estimate that the association constant of the salt bridge formed by porphyrin
phenyl 43 and carboxylate in CH2C12 is also in a similar range of 105 — 106 M", depending

upon which benzoate is used.

III. PCET Studies

The ET rates have been measured in dichloromethane by using fluorescence
quenching techniques. The fluorescence of 77 and 72 was quenched by the addition of
electron acceptors 3,5-DNB and 3,5-dinitrobenzamidinium (3,5-DNBA), respectively.
All lifetime quenching measurements showed a biexponential decay in which one
lifetime component was concentration dependent and the other was concentration
independent. The concentration-dependent rate constant was assigned to the bimolecular

ET processes and the concentration-independent rate constant was attributed to ET for the

97

associated pairs.

Figure 15 summarizes the unimolecular ET rates calculated from the decay
kinetics and driving force of the ET reaction for the corresponding coupled system. In
ZnPor (COOH-Am) DNB (72—3,5-DNBA), the salt bridge is aligned in such way, that
the protons are located on the acceptor side and only the electron should transfer. The
intermolecular electron transfer from zinc porphyrin 72 to 3,4-DNBA is 2.0 X 109 s",
which is comparable to the ET through the carboxylic acid dimer.22 In ZnPor(Am-
COOl-I)DNB (77—3,5-DNB), the proton interface is switched, both an electron and
proton may traverse the proton interface. In this case, the intermolecular ET rate is
significantly slow (k,, = 6.4 X 107) although it possessed a similar driving force as
ZnPor(COOH-Am)DNB. This dramatic difference in rates for ZnPor(Am-COOIDDNB
and ZnPor(COOH-Am)DNB may have several origins. First, the electron transfer is in
the direction of the permanent dipole of the salt bridge. The presence of an internal
electric field contained within the electron transfer pathway may alter the driving force of
reaction. Secondly, the proton may shift within the salt bridge and cause significant
additional contribution to the Frank-Condon factor.

Determination of the ET rates in decoupled systems, using the method described
previously, yielded the rate constants shown in Figure 16. As with ZnPor(Am-
COOH)DNB and ZnPor(COOH-Am)DNB, ZnPoerh(Am-COOH)PhPorFe(III) and
ZnPoerh(COOH-Am)PhPorFe(III) are assembled through a salt bridge. Therefore, the
internal electric field is retained between the donor and acceptor, but the proton interface
is decoupled from the porphyrin in a Franck Condon sense by the introduction of a

phenyl spacer. In this case, switching the proton interface has little effect on the

98

observed ET rates in these systems. These preliminary PCET studies reveal that proton
shifting may be responsible for the observed slow ET process in the coupled systems.
Nevertheless, because the distances between the donor and acceptor are different in these
two systems, the effect of the permanent dipole associated with the salt bridge is not easy
to address. Therefore the new systems based on purpurin and chlorin molecules have

been designed and will be discussed in the next Chapter.

IV. Conclusions

This study has demonstrated that the electron donor/acceptor pairs juxtaposed by
the amidinium-carboxylate salt bridge can be formed through self-assembly in solution.
Hydrogen bond distances within amidinium-carboxylate salt bridge are in the range from
2.70 to 2.80 A, indicating a very stable salt bridge in the solid state. In solution, the
stability of the salt bridge is retained, as revealed by strong binding in DMSO despite its

high dielectric constant.

99

kPCET = 7.3 X 107 5.1
AG = —0.42 V

 

ZnPor(Am-COOH)DNB

9 s—1

kPCET=ZX1O
AG=-0.45V

 

ZnPor(COOH-Am)DNB

Figure 15. Summary of ET rates in coupling system

100

 

kpcET / 5" AG IV vs SCE

- O-H--O
ZnPorPh(COOH)2PhPorFe(III) —(\ >— 0.76 x109 —1.11
o---H-o
H\
N-H--O
ZnPorPh(Am-COOHPhPorFe(III) (a é>— 1,4 x 109 -(14
,N-Hn-o
H
’H
O---H-N
ZnPorPh(COOH-AmPhPorFe(llI) «9 GI)— 2.1x109 —1.o4
O--H-N
H

Figure 16. Smnmary of ET rates in decoupling systems

101

V. Experimental

A. Crystallography

The single crystal suitable for crystallographic study was grown in acetonitrile
using a 1:1 mixture of nickel porphyrin arrridinium chloride and tetrabutylammonium
benzoate. The crystal used for analysis was of the approximate dimension 0.05 x 0.50 x
1.50 mm. Data collection was performed on a Nonius diffractometer at room
temperature using graphite-monochromated Mo Kat radiation. The unit cell parameters
were determined by a least square fit of 25 machine-centered reflections having 20 values
in the range of 19.00-24.44°. The intensity data were reduced and corrected for Lorentz
and polarization factors using the applied programs. The crystal structure was solved by
direct methods using the NRCVAX program package and 1045 parameters were refined
to R = 0.065 (Rw = 0.058). All non-hydrogen atoms were refined anisotropically. The
hydrogen atoms were placed at calculated positions with fixed isotropic thermal

parameters.
B. Binding studies

1. 1H NMR

1H NMR binding studies were performed on a VXMR 500MHz NMR
spectrometer using DMSO-d,5 (Cambridge Isotope). 1H NMR binding studies consisted
of incremental additions of small volumes (1-2 111) of a concentrated guest solution to a
large volume (700 111) of a host solution. The total volume change was less than 5%.
After each addition of titrant (the guest solution), the 1H NMR spectrum of the system

was recorded. Changes in the spectrum of the host were plotted against the concentration

102

of the added guest. The guest concentration was known from the amount of guest
solution added and the resulting voltnne change. The resulting data points were fitted
using KaleidaGraph and the Wilcox’s titration equation.68 to determine the association
constants.
2. Ultraviolet-Visible Absorption Spectroscopy Study

The UV-vis absorption experiments were performed with a Cary-17 spectrometer.
The experiments were carried out in spectral grade dichloromethane distilled over
calcium hydride or DMSO distilled under reduced pressure over barium oxide. A quartz
cuvette capable of holding 5 ml of sample and possessing a stopper was employed in all
of the binding studies. The binding study consisted of incremental additions of small
volume (2-5 111) of a concentrated guest solution to large volume (5 ml) of a host solution.
The total volume change was less than 1%. After each addition of guest, the spectrum
was recorded and the changes in absorbency intensities were recorded. The
concentration of the guest in the cuvette at each addition was calculated based on the
guest’s stock solution concentration. Changes in the absorbency intensity were plotted
against the guest concentration to obtain the binding isotherm. The association constants

were then determined using the same method described for the NMR binding study.

Chapter IV

Purpurin and Chlorin

— Synthesis and Electron Transfer

1. Introduction

PCET studies of the porphyrin systems of Chapter III disclose that amidinium-
carboxylate salt bridge internal to the ET pathway can profoundly regulate ET rates.
While the results are striking, the system is not an optimally designed one. The method
of decoupling the proton interface from the porphyrin has been achieved through the
introduction of a phenyl spacer at the mesa position. This modification changes the
distance between donor and acceptor as well as the position where the proton interface is
attached. Such changes may also alter the effect of the permanent dipole of the salt
bridge on ET. Therefore, it is not appropriate to compare the coupled system to the
decoupled system. Thus, the challenge of this project is to couple and decouple the ET
chromophore from the salt bridge in a system sharing the same structural features.

In the course of total synthesis of chlorophyll a , Woodward et al.‘59 discovered

103

104

that when porphyrin mesa-acrylic ester was refluxed in acetic acid under inert atmosphere,
an equilibrium was established between the porphyrin and purpurin, with an equilibrium
constant of 1.7. This cyclization, aided by steric crowding and the electron-withdrawing
power of the ester group,” was repeated by Fuhrhop7| and Morgan72 to convert mesa-
acrylic OEP 80 to the corresponding purpurin ester. Morgan further demonstrated that
the double bond of the cyclopentenyl ring of purpurin ester 81 could be selectively
reduced to a single bond to form chlorin 82 by hydrogenation in the presence of a

catalytic amount of Pd/C (SghemsLlfi).

 

80 purpurin 81 Chlorin 82

Scheme 14

Such purpurin/chlorin structures are particularly attractive to us. In purpurin 81,
the double bond of the cyclopentenyl ring enables chromophore conjugation with the
external ftmctional group. In chlorin 82, such conjugation is interrupted by the reduction
of the double bond to a single bond. Unlike the porphyrin systems, the number of bonds
between the chromophore and proton interface will remain the same, as does the distance.
The conversion between the purpurin and chlorin thus provides an ideal way to modulate
the coupling or decoupling of the chromophore and proton interface. For our studies, the

ester group should be replaced with either an amidinium or a carboxylic acid group. This

105

Chapter describes the synthesis and PCET studies of purpurin and chlorin analogous of

81 and 82.

II. Results and Discussion
A. Synthesis

1. Purpurin and chlorin carboxylic acid

In Schmli, the synthesis was initiated from nickel octaethyl-porphyrin (OEP).
According to the method of Morgan,72 nickel OEP was converted to nickel mesa-formyl
OEP 78 with the Vilsmeier reagent. Porphyrin aldehyde 78 was treated with
(carbethoxymethylene)triphenylphosphorane to give nickel mesa-[B-(ethoxy-
carbonyl)vinyl]octaethylporphyrin 79. Subsequent demetallation with concentrated
sulfuric acid (to yield the porphyrin 81) and cyclization in refluxing glacial acetic acid
under nitrogen afforded the corresponding (ethoxycarbonyl)octaethylpurpurin 81 in 72%
yield. The use of free base was essential for the cyclization because the initial step of the
cyclization involved the protonation of porphyrin nitrogen.73 Evidences supporting the
formation of 81 were given by mass spectrometry, which indicated a product isomeric
with the reactant, and by the lH NMR Spectrum of 81. The Signals associated with the
acrylate protons in 81 (doublets at 8 10.40, 6.20 ppm) were no longer present in the
spectrum of cyclized product, which instead contained a singlet at 8 9.40 ppm attributable
to the olefinic proton of the cyclopentenyl ring. Of the four mesa protons, one was
shifted upfield approximately 1 ppm, which was indicative of its placement adjacent to a
reduced pyrrole ring.74 In addition, both methyl and methylene resonances of a peripheral

ethyl group exhibited upfield shifts of approximately 1 ppm, consistent with their

106

presence on a nonplanar reduced pyrrolic ring.75 Finally, the visible spectrum of the 81
gave a purpurin-type spectrum, with the absorption of band I appearing at 695 nm.

The conversion of purpurin 81 to 82 was based on the method described by
Morgan.72 Catalytic hydrogenation of 81 with 10% Pd/C resulted in the reduction of this
molecule to the porphyrinogen as evidenced by loss of the color in the resulting solution.
Filtration to remove the catalyst followed by vigorous stirring in the presence of air
quickly reoxidized the macrocycle to give a deep blue/ green solution from which the
product 82 was isolated in 71% yield. The formation of the product as 82 was based on
the mass spectrum (confirming addition of 1 mole of hydrogen), the visible spectrum,
which resembled that of a chlorin76 (km 662 nm), and the 1H NMR spectrum, which
confirmed the integrity of the carbon skeleton but lacked the signal attributable to a
cyclopentenyl proton.

Initial difficulties were encountered when ester 81 was hydrolyzed with sodium
hydroxide in ethanol. However, when the reaction was carried in pyridine, the hydrolysis
went smoothly. Both 81 and 82 were hydrolyzed by this method and were converted to
83 and 85, respectively. Corresponding zinc complexes 84 and 86 were then obtained by

regular zinc insertion procedures (ZnCl2 /DMF).
2. Purpurin and chlorin arrridinium

The synthetic strategy used to derive the amidinium compound is similar to that
described previously for making porphyrin amidinium 75. Thus, the first step of the
synthesis of 92 was to make purpurin nitrile 89. As described in Scheme-.16, diethyl

cyanomethyl-phosphonate was treated with 1 eq. of sodium hydride to generate a Wittig

C

1 if

82

2!:

20(ACO)2

g!

107

 

POCI3/ PhaPCHzcozfit / c0251
—-—> CHO '
DMF
78 79

1. con. H 304
2. N82CC§3

H2, Pd/C HOAc / c0251
*— Cl .___.
0251 COzEt
H
80

81
l NaOH/pyridine \NaOH/pyn’dine

85 w 83
COOH COOH
H

Zn(AcO)2

86 I 84
COOH COOH
H

Scheme 15

108

reagent, which reacted with nickel mesa-fonnyloctaethylporphyrin 78 to give nickel
mesa-([3-cyanoethenyl)-octaethylporphyrin 87 in 87% yield. After demetallation with
concentrated sulfuric acid, free base 88 was obtained. In 88, the steric effect and electron
withdrawing properties of the porphyrin were similar to that of porphyrin 80. Therefore,
we expected that 87 should undergo similar cyclization to give the corresponding
purpurin 89. To accomplish the cyclization, 88 was refluxed in glacial acetic acid under
nitrogen. After purification by column chromatography and crystallization, a purple
crystalline product was obtained. Its UV-vis spectrum was similar to that of 81 with the
absorption band I appearing at 692 nm. The mass spectrum indicated that the product
was isomeric with the reactant 88. Also in the 1H NMR spectrum, signals associated with
vinyl protons in 88 (doublets at 8 10.06, 5.58 ppm) were no longer present in the
spectrum of product 89, which contained instead a singlet at 8 9.20 ppm attributable to
the olefinic proton of the cyclopentenyl ring. One mesa proton as well as both methyl
and methylene resonances of a peripheral ethyl group exhibited upfield shifts of
approximately 1 ppm, which was similar to that observed in 81. In addition, the IR
spectrum revealed a peak at 2235 cm", providing the evidence for the presence of a
nitrile group in the product.

With the purpurin nitrile in hand, the conversion of 89 to 92 was achieved using
the methodology described in Chapter II. Purpurin 89 was refluxed with nickel acetate in
DMF to give the nickel complex 91, which was then treated with chloromethylaluminum
amide to effect the conversion of 91 to 92. Spectral data supported the formation of
anridinium 92. Two broad NH peaks appeared at 8.80 and 8.96 ppm in the proton NMR

of 92, indicating of the formation of the amidinium group. Also, the nitrile stretching

109

band (2235 cm") was no longer present in the IR spectrum of 92, and instead was
replaced by a band at 1653 cm", which is attributable to the C=N stretching of the
amidinium group.

Catalytic hydrogenation of 89 with 10% Pd/C resulted in reduction of the
molecule to the porphyrinogen, which was vigorously stirred in the presence of air to
reoxidize the macrocycle to give 90 in 75% yield. The formation of the product as 82 is
based on its mass spectrum (confirming addition of 1 mole of hydrogen), the chlorin type
visible spectrum77 (71max 662 nm), and its 1H NMR spectrum, which confirmed the
integrity of the carbon skeleton but lacked the signal attributable to a cyclopentenyl
proton. After nickel insertion, 95 was converted to amidinium 96 with C1A1(NH2)CH3
using the methodology described previously in 93% yield. Both NMR and MS gave
satisfactory results. Later it was found that chlorin amidinium 96 could be directly
derived from purpurin amidinium 92. When 92 was hydrogenated with 10% Pd/C, it was
converted to 96. This demonstrated that amidinium group was stable to hydrogenation.

After demetallation with concentrated sulfuric acid (to yield fiee bases), 92 and
96 were converted to corresponding zinc complexes 94 and 98, respectively, using zinc

chloride in DMF.
B. Coupling vs. Decoupling

In order to determine the electronic coupling between the chromophore and the
proton interface in purpurin and chlorin complexes, we utilized the same methodology
described in Chapter II by examining the pH dependence of their absorption spectrum.
Figure 17 shows the spectral changes associated with deprotonation of purpurin

anridinium 92 in CHZClz. The arrows indicate the spectral shifts observed upon addition

110

 

(EtO)2P(O)CH2CN / CN
NaH, THF
87
1. con. H 04
2. N8 3
H2. Pd/C
4——
NI(ACO)2 N1(ACO)2
Of or
Zn(AcO)2 Zn(A90)2
95 M - NI 91 M - NI
HC.3
HacAl-NHZ I toluene Al-NHZ ltoluene
CI Cl

98. 1111-111 9241-111

sun-211 9301-211

98. 111-211 9“an
cr

   

Scheme 16

111

of DBU in CH2C12 to 92. It can be seen that the deprotonation of the amidinium group of
92 results in blue shifts in the visible absorption maxima along with the Sharpening of the
Soret band. The set of absorption spectra contains isosbestic points at 434, 620 and 658
nm. This process was also found reversible and the original spectra could be recovered
by the addition of CH2C12 saturated with 70% of HClO4. The perturbation of the
absorption profile upon deprotonation of amidinium suggests that the purpurinic
chromophore of 92 is strongly coupled to the amidinium group that constitutes interface.
Such changes were not observed in chlorin 96 upon deprotonation of the
amidinium group. Figure 18 shows the spectra of 96 in the presence of various
concentrations of DBU in CHZClz. It can be seen that deprotonation of amidinium group
of 96 results in no significant shift of the spectra. Compared to 92, the lack of change in
the absorption profile upon deprotonation of chlorin 96 thus suggests that the chlorinic

chromophore of 96 is decoupled to the amidinium and correspondingly to the interface.
C. Binding Studies

The abilities of the purpurin and chlorin amidinium to form a salt bridge with
benzoate in DMSO were studied using 'H NMR. Upon stepwise addition of benzoate,
the internal protons of amidinium exhibited downfield shift due to the formation of
hydrogen bond with oxygen of the benzoate. Figure 19 shows the NMR spectra of
purpurin amidinium 92 in the presence of various concentration of tetrabutylamonium
benzoate in DMSO-d6. Consistent with the porphyrin system, the chemical shift of the
mesa proton remains unchanged and excludes the possibility that the interaction between
the porphyrin and benzoate is due to n-n stacking. The association constants determined

by this method for these systems are listed in Table 6. AS in the previous porphyrin

112

 

 

 

 

 

 

 

 

1.00 i
0.80 - $
0.60 -
10'
.0
<
0.40 - t
1
0.20 *7"? /%\
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000 I l l l I L l “

350 400 450 500 550 600 650 700

Figure 17. Absorption spectra of purpurin 92 (0.81 uM) in the presence of 0.00, 0.20,
0.40, 0.60, 0.80, 1.00, 1.40, 1.80, 2.40 eq. of DBU in CHZCIZ. The arrows represent the

increasing of DBU.

113

 

0.8

0.7

0.6

0.5

0.4

Abs.

0.3

0.2

0.1

 

 

 

0.0
350 400 450 500 550 600 650 700

71 (nm)

Figure 18. Absorption spectra of chlorin 96 (0.93 uM) in the absent (—) and present of
3.00 ( ------- ) eq. of DBU in CHzClz.

114

systems, these association constants are too large to be determined by NMR titration
using CH2C12 as solvent. Thus, UV-vis was used to monitor the formation of salt bridge.
However, this method is only applicable to purpurin 92, in which the chlorinic
chromophore is coupled to the amidinium. The binding constants determined by this
method are also listed in Table 6. For the case of 96, the lack of spectral Shifts obviated

the determination of association constant by UV-vis.
D. PCET Studies

The C=C double bond in purpurin 84 and 94 and the C—C single bond in 86 and
98 allow us to turn on and off the coupling between the chlorinic chromophore and the
proton interface, respectively. Thus, this unique structural feature of the purpurins and
chlorins provides us an opportunity to study proton-coupling effects. The PCET model
systems are shown in Figure 23. The supramolecular complexes, ZnPur(Am-
COOH)DNB (94—3,5-DNB), ZnPur(COOH-Am)DNB (84—3,5-DNB), ZnChl(Am-
COOH)DNB (98—DNBA), and ZnChl(COOH-Am)DNB (86—3,5-DNBA) feature
(pmpurin and chlorin) zinc donors and dinitroaromatic acceptors separated by a fixed
distance ensured by the external five member ring, which locks the salt bridge. The
number of bonds along the electron transfer pathway is also fixed, ensuring that
modification only impacts the coupling between the chromophore and proton interface, as
well as the directionality of proton transfers. Table 7 lists the D—A separation of these
systems.

The ET studies were performed in an analogus manner as described chapter 111.
Photoexitation of 84, 94, 86 and 98 in CHZCl2 produced the highly reducing singlet exited

state molecules having intrinsic fluorescent lifetime of 0.95, 0.91, 1.46 and 0.98 ns.

115

 

 

 

 

C

.....J
I l l 1
14.0 13.0 12.0 11.0 10.0 9.0 8.0

PM“

 

 

 

Figure 19. Selected 1H NMR spectra of 96 (3.86 mM) with 1 eq. of benzoic acid in the
absence of and in the presence of 1.00, 1.69, 2.38, 3.08, 5.16, 7.23, and 10.00 mM
(bottom to top) of tetrabutylammonium benzoate in DMSO-d6 at room temperature. The
spectral range captures the amidinium protons internal (N Hi“) and external (N Hex) to the
salt bridge interface and the three mesa protons of the purpurin as well as olefinic proton

of the cyclopentenyl ring.

116

 

12.5

12.0

11.5

11.0

10.5

8 ppm

10.0

9.5

 

9.0 t

 

 

I I l l l l

 

8.5
0 0.002 0.004 0.006 0.008 0.01 0.012 0.014

[Carboxylate] (M)

Figure 20. Plot of the chemical Shift of internal protons of the amidinium versus the

concentration of tetrabutylamonium benzoate

117

 

1.2

1.0

0.8

0.6

Abs.

0.4

0.2

 

 

2W

 

 

 

0.0

Figure 21. Selected UV-vis spectra of 92 (2.74 uM) in the presence of 0.0, 0.63, 1.26,
1.88, 2.51, 3.14, 4.40, 5.65 and 7.54 uM (increase with arrows) of tetrabutylammonium
benzoate in dichloromethane.

118

 

0.20

0.15 '

5 0.10 —

0.05 -

 

 

 

0.00 r r I r r
0.00 2.00 4.00 6.00 8.00 10.0 12.0

[Benzoate] x 10’‘3 (M)

Figure 22. Plot of the absorption change of 92 at 420 nm versus the concentration of

tetrabutylammonium benzoate

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120

When the corresponding 3,5-dinitroaromatics (3,5-DNB or 3,5-DNBA) were present,
biexponential decays were observed. ET rates were determined by analysis of the
fluorescence decay kinetic profiles as a function of the concentration of corresponding
dinitroaromatics. In all system, it was found that one lifetime component was
concentration-dependent and the other was concentration-independent. The
concentration—dependent rate constant was assigned to the bimolecular ET processes and
the concentration-independent rate constant was attributed to ET for the associated pairs.
The unimolecular ET rates for these systems measured by this method, as well as the
driving force of the ET reaction of each system, are summarized in Table 7. Before
discussing the role played by proton coupling in the salt bridge, the impact of the
permanent dipole moment associated with the salt bridge on the photoinduced ET rate
must be addressed.
According to the classical and semiclassic ET theory, the ET rate constant kET can
be expressed as
kET = (211/ h)VR2(FC) (4. 1)
where V is the electronic coupling term that is distance dependent. PC is F ranck-Condon

factor and is expressed as:

 

 

l G *
PC = exp (4- 2)
4nkkBT kBT

where kB and T are, respectively, Boltzmann’s constant and the temperature. 6* is the
energy barrier for the ET reaction. According to the Marcus ET theory", it is expressed

as:

_ (AG0 + 102
47.

G“ = (4. 3)

121

where I. is the reorganization energy containing contributions from solvent, as well as

from molecular vibration of the donor-acceptor system; AG0 is the standard free energy
of reaction (negative of the driving force). Because of the permanent dipole moment of
the salt bridge, we expect the free energy of the ET reaction in ZnPur(Am-COOH)DNB
and ZnChl(Am-COOH)DNB will be affected differently compare to that in
ZnPur(COOH-Am)DNB and ZnChl(COOH-Am)DNB. In ZnPur(Am-COOI-DDNB and
ZnChl(Am-COOIDDNB, the electron transfer opposes the dipole moment and therefore
the ET will be energetically less favorable. Whereas, in ZnPur(COOH-Am)DNB and
ZnChl(COOH-Am)DNB, the electron transfer is along the dipole moment and thus the
ET reaction is more exothermic. Because the D-A separations for the four assemblies are
the same, the free energy change associated with the permanent dipole from ZnPur(Am-
COOH)DNB to ZnPur(COOH-Am)DNB and that from ZnChl(Am-COOH)DNB to
ZnChl(COOH-Am)DNB should be the same in the same solvent. If dipole moment
effects dominated the ET kinetics in these systems, the ET rate difference between
ZnPur(Am-COOIDDNB and ZnPur(COOH-Am)DNB should be similar to that between
ZnChl(Am-COOH)DNB and ZnChl(COOH-Am)DNB. However, this is not the case. A
comparison of photoinduced ET rate data between ZnPur(Am-COOH)DNB and
ZnPur(COOH-Am)DNB Shows that switching the proton interface has a dramatic impact
on ET rates for the purpurin system. For the chlorin system, switching the proton
interface had only a minor effect when one compares the ET rates of ZnChl(Am-
COOH)DNB to ZnChl(COOH-Am)DNB. The huge difference of ET rate constants
between ZnPur(Am- COOH)DNB and ZnPur(COOH-Am)DNB compared to that

between ZnChl(Am-COOH)DNB and ZnChl(COOH-Am)DNB implies factors other than

122

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124

the dipole moment of salt bridge are involved in the ET reaction.

According to eq. 4.3, the Franck Condon factor is determined by both the driving
force and the reorganization energy (A) of the ET reaction. Reorganization energy
occurs because the electron transfers at a much faster rate than the movement of solvent,
and the solvent does not have enough time to adjust its dipole moment to optimize the
solvation energy. Thus the ET product forms in a high-energy state; the energy required
to relax to equilibrium is the reorganization energy. Therefore, the magnitude of A. is
determined by the solvent and the size of electron donor and acceptor (the larger size of
D-A molecule is, the less density of charge on its surface, and less reorganization energy).

Marcus proposed that for a certain ET reaction, A can be expressed as:
x = charm“ + Om)" —(RDA)“1(e;‘ + sop“) (4. 4)

where e is the charge of an electron, a, is the static and cop is the high frequency dielectric
constant of the solvent, rD and rA is the radii of donor and acceptor, respectively and Rm.
is their separation.

In ZnChl(Am-COOI-DDNB and ZnChl(COOH-Am)DNB assemblies, the chlorin
chromophores are decoupled from the salt bridge, and the ET event is independent from
what happens at the salt bridge. Thus, ET reactions in these complexes behave normally.
The ET rate differences between ZnChl(Am-COOH)DNB and ZnChl(COOH-Am)DNB
reflect only the dipole moment effect of the salt bridge. However, the situation is more
complicated for the purpurin systems. Wasielewski79 has demonstrated that the
reorganization energy for similar covalently linked Zn(II) porphyrin donor-acceptor
systems is 0.9 eV. The ET driving force for ZnPur(Am-COOH)DNB and ZnPur(COOH-

Am)DNB are 0.54 eV and 0.53 eV respectively. From eq. 4.3, the increase of the

125

reorganization energy should decease the ET rate because -AG° < A for these systems.
This is exactly what we observed in our experiments. In ZnPur(Am-COOIDDNB, the
photoinduced ET reaction produces a positive charge on purpurin 94. Since the
chromophore of 94 is coupled to the amidinium of the salt bridge, the presence of the
positive charge will decrease the pKa of the amidinium group. On the donor side, the ET
event results in a negative charge on 3,5-DNB and the pKa of the carboxylate group will
increase. Such changes in pKa within the salt bridge will most likely drive the proton
across the interface and the whole system will be stabilized by the proton transfer. This
is not the case for ZnPur(COOH-Am)DNB. Here the proton is already residing on the
acceptor, and hence it is likely to remain upon the arrival of the electron. Like the
electron transfer, proton transfer can give rise to reorganization energy due to its positive
charge. Hence, there is reorganization energy associated with ET and PT in ZnPur(Am-
COOI—DDNB, whereas for the case of ZnPur(COOH-Am)DNB, there is a reorganization
energy that arises from ET only. This extra reorganization energy is believed to be
responsible to the slow ET rate in ZnPur(Am-COOH)DNB.

In summary, comparisons of ET rates in the chlorin systems rule out the
permanent dipole moment of the salt bridge as the major factor for the large ET rates
difference between ZnPur(Am-COOH)DNB and ZnPur(COOH-Am)DNB of purpurin
systems. Instead, that proton transfer within the salt bridge is believed to contribute to
the slow electron transfer in ZnPur(Am-COOIDDNB. The relocation of proton causes

extra reorganization energy for the ET reaction, thus giving rise to the slower ET rate.

126

V. Experimental

Freshly distilled phosphoryl chloride (2.74 ml) was added dropwise to dry DMF (2 m1)
cooled in an ice-bath, and the solution was kept at room temperature for 30 min. Then
the mixture was warmed up on water bath to 50 °C and a solution of Ni-OEP (500 mg,
mol) in dry 1,2-dichloroethane (300 ml) was added dropwise with vigorous stirring,
maintaining the temperature at 50 - 55 °C over a period of 15 min. The solution was then
warmed for a further 1 h, a saturated solution of sodium acetate (200 ml) was added, and
stirring and heating were wontinued for a further 2 h. The organic phase was separated
and the water phase extracted with dichloromethane twice, which was added to the
organic layer. The solvents were removed under reduced pressure and the residue was
dissolved in dichloromethane and chromatographed on silica gel (CHZCI2 eluent). The
title compound was obtained in 85% yield. UV-vis: l 402, 561, 643 nm; IH NMR (300
MHz, CDCl,) 8 1.70 (24H, m, CH3 of ethyl), 3.70 (16H, m, CH2 of ethyl), 9.27 (2H, s,

mesa H), 9.30 (1H, s, meso H); MS found m/e 618; clcd 618.29 for C37H44N4Ni0

”.11 'CB'1 1 I] I; ll 1 .15
A solution of nickel meso-formyloctaethylporphyrin 78 (506 mg, 0.82 mmol) and
(carbethoxyrnethylene)triphenylphosphorane (1.024 g, mol) in xylene (50 mL) was
heated under reflux for 18 hours. After the solution was cooled, the solvent was removed
in vacuo and the resulting solid chromatographed on silica by using dichloromethane for

elution. A minor fraction of nickel OEP was collected first, followed by a major red band.

127

Collection, removal of solvent, and crystallization of the resulting residue from
dichloromethane-methanol gave the product (455 mg, 0.66 mmol) in 81% yield. m.p.
228-230 °C; UV-vis: km, 405, 530, 565 nm; 1H NMR (300 MHz, CDCl,) 5 1.30 (3H, t,
CH3 of ethyl ester), 1.75 (24H, m, CH, of peripheral ethyl), 3.78 (16H, m, CH2 of
peripheral ethyl), 4.28 (2H, q, CH2 of ethyl ester), 5.25 (1H, d, a-H of acrylic ester),
9.41(3H, s, mesa H), 10.08 (1 H, d, B-H of acrylic ester); MS (CI 70 eV), m/e 688, clcd

688.32 for c,,H,,N,o,Ni

To a solution of the nickel complex 79 (455 mg, 0.66 mmol) in dichloromethane (80 mL),
concentrated sulfuric acid (10 mL) was added and the mixture was kept stirred until all
the porphyrin was extracted to the sulfuric acid layer. Ice (50 g) was added, followed by
saturated aqueous sodium carbonate. After neutralization, the organic layer was collected,
washed, and dried and the solvent was removed. Crystallization of the crude product
from dichloromethane-methanol gave 80 ( 416 mg, 0.66 mmol) in 98% yield. m.p. 215-
216 °C; UV-vis: Am 405; 530, 565; 1H NMR (300 MHz, CDCl,) 5 -3.10 (2H, b, NH),
1.42 (3H, t, CH3 of ethyl ester), 1.64 (6H, t, CH3 of 3, 7-ethyl), 1.90 (18H, m, CH3 of
peripheral ethyl), 3.90 (4H, q, CH2 of 3, 7-ethyl ), 4.1 (12H, m, CH2 of peripheral ethyl),
4.43 (2H, q, CH2 of ethyl ester), 6.18 ( 1H, d, a-H of acrylic ester), 9.92 (1H, s, mesa H),
10.06 (2H, s, mesa H), 10.38 (1 H, d, B-H of acrylic ester); MS (CI 70eV), m/e 632, clcd

632.41 for C41H52N4O2

.. no 11’ - 3-' u. . nu ‘ 0‘. 0 .-.'o mm"! 00 It It:

128

A solution of 80 (416 mg, 0.66 mmol) in glacial acetic acid (80 ml) was heated under
reflux in a nitrogen atmosphere for 24 hours. The solvent was removed in vacuo and the
residue was dissolved in dichloromethane. Chromatography on silica with
dichloromethane as eluant gave a major green fraction. Removal of the solvent and
crystalliztion from dichloromehtane-methanol gave purple microcrystals of 81 ( 300 mg,
72 % yield). UV-vis 7km, 433, 453, 503, 530, 568, 648, 695; 1H NMR (300 MHz, CDCl,)
8 -1.05, -0.42 (each 1H, s, NH), -0.21 (3H, t, CH 3 of 3-ethyl), 1.75 (24 H, m, CH3 of
peripheral ethyl), 2.50, 2.9 (2H each, m, CH2 of 1, 2-ethyl), 3.80 (m, 13H, CH2 of
peripheral ethyl, C-2 H), 4.00 (2H, q, CH2 of ethyl ester), 9.20 (1H, s, H of isocyclic ring),
8.44, 9.48, 9.51 (each 1H, s, mesa H); MS (CI 70eV), m/e 632, clcd 632.41 for

C41H52N402

H 1 . EB . C] l . 82
Palladium on charcoal (10%) (20 mg) was added to a stirred solution of purpurin ester 81

(100 mg, 0.16 mmol) in THF (20 mL) containing triethylamine (2 drops). The reulting
mixture was hydrogenated at room temperature, under a slightly positive pressure. After
stirring overnight, the reaction mixture was filtered and the solution obtained vigorously
stirred in air for 2.5 h. Afier complete oxidation of the intermediate porphyrinogen,
follwed by measuring the increasing intensity of an absorption at 660 nm in the visible
spectrum, the solvent was removed in vacuo and the residue chromatographed on silica
gel with 1% methanol in dichloromethane. The major blue band was collected, the
solvent removed, and the crude product crystallized from dichloromethane-methanol to

give the product (72 mg, 0.11 mmol) in 71% yield. UV-vis km 403, 500, 535, 558, 610,

129

660 nm; 1H NMR (300 MHz, CDCl,) 5 -2.00, -1.38 (each 1H, s, NH), -0.20 (3H, t, CH 3
of 3-ethyl), 1.55 (3H, t, CH3 of ethyl ester), 1.75 (21H, m, CH3 of peripheral ethyl), 2.80,
3.10 (2H each, m, CH2 of 2, 3-ethyl), 3.85 (m, 12H, CH2 of peripheral ethyl, ), 4.45 (2H,
m , CH2 of ethyl ester), 4.46 (1H, m, C-2 H), 4.65, 4.82, 5.22 (1H each, m, H of isocyclic
ring), 8.68, 9.58, 9.60 (each 1H, s, mesa H); MS (CI 70eV), m/e 634, clcd 634.41 for

C41H54N402

E . l l' . l 83
A solution of purpurin ester 81 (100 mg, 0.16 mmol) in pyridine (15 ml) was heated to

reflux under nitrogen and sodium hydroxide (1 g) in water (2 ml) was added. The
mixture was then allowed to reflux overnight. After cooling to room temperature, water
was added and the mixture was extracted with dichloromethane (15 ml) three times. The
organic layer was combined and washed with water, dried over sodium sulfate. The
solvent was removed under reduced pressure and residue chromato graphed on silica with
3% methanol in dichloromethane. The crude product was crystallized from
dichloromethane-methanol to give 83 (77 mg, 0.13 mmol) in 80% yield. m.p. >275 °C;
UV-vis Am 428, 502, 526, 566, 639, 694; 1H NMR (DMSO-d.) 8 -1.22, -0.58 (each 1H,
s, NH), -0.35 (3H, t, CH 3 of 3-ethyl), 1.75 (24H, m, CH3 of peripheral ethyl), 2.70, 3.15
(2H each, m, CH2 of 2, 3-ethyl), 3.80 (m, 13H, CH2 of peripheral ethyl, C-2 H), 4.02 (2H,
q , CH2 of ethyl ester), 9.24 (1H, s, H of isocyclic ring), 8.78, 9.52, 9.54 (each 1H, s,

mesa H), 12.62 (1H, s, carboxylic acid H); MS (FAB), m/e 605.2 (MH+), clcd 605.37 for

C39H49N402

130

General procedure for line insertion:

Zinc acetate (100 mg) was added to a solution of purpurin or chlorin (0.1 mmol) in DMF
(15 mL) and the mixture refluxed until chelation was complete (monitored by both UV-
vis and TLC, ca. 5 min). The mixture was added to water and extracted with
dichloromethane. The organic layer was washed with water several times. After removal
of solvent, the solid residue chromatographed on silica gel (eluted with 3% methanol in

dichloromethane) to give the product.

Z. . l I. . l 8 |
95% yield. m.p. 261-262 °C; UV-vis km” 436, 532, 579, 615, 662; MS (FAB) found We

666.2 (M*), clcd 666.29 for c,,H,,N,o,Zn

[211' l l' '185

To a solution of chlorin ester 82 (72 mg, 0.11 mmol) in pyridine (10 mL), sodium
hydroxide (0.5 g) in water (1 mL) was added. The mixture was heated to reflux for 2 h
under nitrogen. After cooling, water was added and the mixture was extracted with
dichloromethane (10 mL) three times. The organic layer was combined, washed with
water and dried over sodium sulfate. The solvent was removed under vacuo and the
residue chromatographed on silica gel with 7% methanol in dichloromethane. The crude
product was crystallized from dichloromethane-methanol to give chlorin 85 (54 mg, 0.88
mmol) in 81% yield. m.p. >275 °C; UV-vis Am, 401, 499.5, 558, 558, 608, 662; 1H NMR
(300 MHz, CDCl,) 8 -2.02, -1.44 (each 1H, 5, NH), -0.18 (3H, t, CH 3 of 3-ethyl), 1.78

(24H, m, CH3 of peripheral ethyl), 2.08 (2H, m, CH2 of 2-ethyl), 2.80, 3.10 (2H each, m,

131

CH2 of 2, 3-ethyl), 3.90 (m, 12H, CH2 of peripheral ethyl, ), 4.45 (2H, m, CH2 of ethyl
ester), 4.46 (1H, m, C-2 H), 4.65, 4.82, 5.22 (1H each, m, H of isocyclic ring), 8.68, 9.58,

9.60 (each 1H, s, mesa H); MS (CI 70eV), m/e 606, clcd 606.37 for C3,,H50N4O2

Z. l I . l l' . l 85
95% yield. m.p. >275 °C; UV/vis: 7km 410, 480, 513, 588, 634; MS (CI 706V) found

m/e 668, clcd 668.31 for C39H48N4022n

Diethyl cyanomethylphosphonate (1.0 g, 5.65 mmol) was added dropwise to a solution of
sodium hydride (0.24 g, 60% disperion in mineral oil) in dried THF (10 ml). The
resulting solution was charged with mesa-fonnyloctaethylporphyrin 78 (1.0 g, 1.62 mmol)
in dried THF (20 ml). The mixture was heated under reflux in a nitrogen atmosphere for
1 hour and dichloromethane was added upon cooling to room temperature. The solution
was washed with water three times and the organic layer was collected, dried with
sodium sulfate and the solvent was remove in vacuo. The resulting solid was
chromatographed on silica gel by using dichloromethane/hexane (1/1) for elution.
Crystallization of the resulting residue from dichloromethane-methanol gave the
porphyrin 87 (0.91 g, 1.48 mmol) in 87% yield. m.p. 228-230 °C; UV-vis: 71m 405, 530,
565; 1H NMR (300 MHz, CDCl,) 5 1.75 (24H, m, CH3 of peripheral ethyl), 3.78 (16H, m,
CH2 of peripheral ethyl), 4.58 (1H, d, a-H of acrylic nitrile), 9.41(3H, s, mesa H), 9.72 (1

H, d, B-H of acrylic nitrile); MS (CI 70eV), m/e 641, clcd 641.30 for C39H45N5Ni

132

To a solution of the nickel complex 87 (500 mg, 0.78 mmol) in dichloromethane(80 ml),
concentrated sulfuric acid (15 ml) was added and the mixture was stirred until all the
porphyrin was extracted to the sulfuric acid layer. Ice (50 g) was added, followed by
saturated aqueous sodium carbonate. After neutralization, the organic layer was collected,
washed, and dried and the solvent was removed. Crystallization of the crude product
from dichloromethane-methanol gave the free base (450 mg, 0.78 mmol) in 98% yield.
m.p. 215-216 °C; UV-vis: km, 406, 505,539, 575, 626; IH NMR (300 MHz, CDCl,) 6 -
3.14 (2H, b, NH) 1.80 (24H, m, CH3 of peripheral ethyl), 4.00 (16H, m, CH2 of peripheral
ethyl), 5.58 (1H, d, a-H of acrylic nitrile), 9.96 (1H, s, mesa H), 10.04 (2H, s, mesa H),

10.06 (1 H, d, B-H of acrylic nitrile); MS (CI 70eV), m/e 585, clcd 585.38 for C39H47N,

... Ho 11' o- 1- 5.10'J'I 0 ...‘t OOIOIIIU 00..n,u-°'

A solution of mesa-[B-cyano vinyl]octaethylporphyrin 88 (450 mg, 0.78 mmol) in glacial
acetic acid (80 ml) was heated under reflux in a nitrogen atmosphere for 24 hours. The
solvent was removed in vacuo and the residue was dissolved in dichloromethane.
Chromatography on silica gel with dichloromethane as eluant gave a major green
fraction. Removal of the solvent and crystalliztion fi'om dichloromehtane-methanol gave
purple microcrystals of 89 (368 mg, 81% yield). m.p. >275 °C; UV-vis km 426, 523,564,
635, 692; 'H NMR (300 MHz, CDCl,) 6 -1.05 , ~0.45 (each 1H, s, NH), -0.22 (3H, t, CH3
of 3-ethy1), 1.75 (21H, m, CH3 of peripheral ethyl), 2.50, 2.95 (2H, m, CH2 of 2, 3-ethyl),
3.80 (m, 13H, CH2 of peripheral ethyl, C-2 H), 9.20 (1H, s, H of isocyclic ring), 9.51,

9.48, 8.49 (each 1H, s, mesa H); MS (CI 70eV), m/e 585, clcd 585.38 for C,,H,,N,

133

C] I . . .1 SI]
89 (120 mg, 0.20 mole) was hydrogenated under the condition described previously to
give 88 mg of title compound (75% yield). m.p. >275 °C; UV-vis: Km 402, 498, 558,
610, 660 nm; 1H NMR (300 MHz, CDCl,) 5 -2.35, -1.70 (each 1H, 3, NH), -0.30 (3H, t,
CH3 of 3-ethyl), 1.75 (21H, m, CH3 of peripheral ethyl), 2.10, 2.80 (2H each, m, CH2 of
2, 3-ethyl), 3.85 (m, 12H, CH2 of peripheral ethyl), 4.15 (1H, m, C-2 H), 4.30, 5.02, 5.04
(1H each, m, H of isocyclic ring), 8.45 (1H, s, mesa H), 9.60 (2H, s, mesa H); MS (CI

70eV), m/e 587, clcd 587.38 for C39H47N,

ll'll "'19l

Nickel insertion was accomplished following the procedure described previously. m.p.
>275 °C; UV-vis: 76m, 424, 511, 555, 605, 648; 1H NMR (300 MHz, CDCl,) 8 -0.10 (3H,
t, CH3 of 3-ethy1), 1.65 (21H, m, CH3 of peripheral ethyl), 2.00, 2.65 (2H, m, CH2 of 2,
3-ethyl), 3.55 (m, 13H, CH2 of peripheral ethyl), 3.78 (1H, m, C-2 H), 8.80 (1H, s, H of
isocyclic ring), 7.80 (1 H, s, mesa H), 9.00 (2H, s, mesa H); MS (CI 70 eV), m/e 641,

clcd 641.30 for C39H45N5Ni

11°11 . .1. 1] .152

The nickel purpurin nitrile 91 obtained from last step and dried toluene (20 ml) was
added to a Schlenck tube. After the system was purged with argon three times,
chloromethylaluminum(III) amide (2 mL, 2 mmol) was introduced by a syringe. The

reaction mixture was stirred at 80 °C for 3 days under an argon atmosphere. The reaction

134

mixture was cooled and the aluminum complex was decomposed by carefully pouring the
solution into a slurry of silica gel (5 g) in chloroform. The mixture was stirred for 5 min
and the silica gel was filtered. The filtercake was further washed with methanol.
Evaporation of the filtrate and purification of the residue by chromatography on silica gel
(25% methanol in dichloromethane) afforded the title compound in 81% yield. m.p. 220
°C (dec.); UV-vis: Am, 436, 532, 579, 615, 662 nm; 1H NMR (300 MHz, CDC13) 8 -0.20
(3H, t, CH3 of 3-ethy1), 1.55 (21H, m, CH3 of peripheral ethyl), 2.65, 2.80 (2H each, m,
CH2 of 2, 3-ethyl), 3.60 (m, 13H, CH2 of peripheral ethyl), 4.00 (1H, m, 02 ID, 8.20 (l
H, s, mesa H), 8.80, 8.96 (2H each, b, NH of amidinium), 9.10 (1H, s, H of isocyclic
ring), 9.12, 9.20 (1H each, s, mesa H); MS (FAB) found m/e 659.5 (MH+), clcd 659.33

for C,,H,,N,Ni

Z' . . 1' l l . l 5 |
65% yield. m.p. 248 °C (dec.); UV-vis km, 406, 442, 540, 626, 674; MS (FAB) found

m/e 665.4 (MH+), clcd 665.33 for C39H49N6Zn

”.1 1C]! . "l 25

Nickel insertion was accomplished by following the procedure described previously to
give 95 in 86% yield. m.p. >275 °C; UV-vis: km 401, 492, 582, 626 nm; IH NMR (300
MHz, CDC13) 8 0.15 (3H, t, CH 3 of 3-ethyl), 1.60 (21H, m, CH3 of peripheral ethyl),
1.85, 2.30 (2H each, m, CH2 of 2, 3-ethyl), 3.55 (m, 12H, CH2 of peripheral ethyl), 3.80
(1H, m, C-2 H), 3.92, 4.42, 4.80 (1H each, m, H of isocyclic ring), 7.65 (l H, s, mesa),

9.10 (2H each, s, mesa H); MS (CI 70eV), m/e 643.31, clcd 643.30 for C39H47N3Ni

135

”.11“. '1” ”.155
The chlorin nitrile 95 (110 mg, 0.17 mmol) was treated with chloromethylalurninium
amide using the procedure described previously to afford 116 mg of the title compound in
93% yield. m.p. 255 °C (dec.); UV-vis: km 401, 496, 584, 626 nm; 1H NMR (300 MHz,
CDCl3) 8 -0.50 (3H, t, CH3 of ethyl), 1.60 (21H, m, CH3 of peripheral ethyl), 1.70 1.80
(2H each, m, CH2 of 2, 3-ethyl), 3.50 (m, 12H, CH2 of peripheral ethyl), 3.65 (1H, m, C-2
H), 3.70, 3.82, 4.15 (1H each, m, H of isocyclic ring), 6.95 (2H, br, NH of amidinium),
7.55, 9.00, 9.05 (1H each, s, mesa H), 9.10 (2H, br, NH of amidinium) ; MS (FAB), m/e

661.1 (Mir), clcd 661.34 for C39H33N6Ni

Z. I l . . 1° 1 l . l 98
70% yield. m.p. >275 °C; UV-vis 71.33,, 410, 480, 513, 588, 634; MS (FAB), m/e 667.3

(MH+), clcd 667.35 for C39H33N62n

Chapter V

Synthesis of Water Soluble Porphyrin-Quinone

I. Introduction

The primary photochemical step in photosynthesis consists of the transfer of an
electron from the excited state of a porphyrin chromophore to an acceptor molecule to
generate a transient radical-ion pair. The fundamental factors governing the efficiency of
the light-induced electron transfer process and those that prevent the rapid back electron
transfer in the charge separated species, are not well understood. In order to gain insights
into these factors, there has been much effort expended on the development of potentially
photoactive donor-acceptor model compounds. Most of these consist of a porphyrin
acting as the light absorbing electron donor, and a chemically attached quinone as the
electron acceptor. Since Kong and Loach80 reported the synthesis of first covalently
linked porphyrin-quinone system, a number of groups synthesized covalently linked
porphyrin-quinone complexes in a variety of structures. Strategies used for linking the
donor and acceptor include amide,8| diester and diamide-linked polymethylene chains,”
‘3 rigid triptycenyl84 and bicyclo[2.2.2]octyl85 spacer, “capped”5 structures. Both

fluorescence quenching and transient absorption techniques have been employed to study

136

137

the photo-induced electron transfer process in these systems.

The majority of electron transfer studies involving porphyrin-quinone complexes
have been carried out in aprotic solvents, in which proton transfer effect is not important
to the ET process. However, if the ET reaction is carried in a protic solvent such as
water, the situation is different. In the photo—induced electron transfer reaction, the
quinone is reduced to a semi-quinone, resulting a marked pKa increase at the quinone
(pKa of quinone87 is —1 and that for semi-quinone is 4.188), which then can be protonated
by the solvent. In this case, proton transfer is involved in the ET reaction and may have
significant effect on ET events. Unfortunately, for most porphyrin quinone complexes,
the poor solubility of porphyrin molecules in aqueous solution prevents the ET study
from being carried out in the aqueous solvent. To conduct the ET studies in aqueous
solution, we need to design and synthesize a new porphyrin quinone complex that is
water-soluble

Tetramethylpyridinium porphyrin is well known to be water soluble, therefore we
decided to take advantage of this structure to synthesize our water soluble porphyrin
quinone complex. Molecular dyad 108 illustrates the strategy for such an approach. The
overall structure of 108 is analogous to the triphenylporphyrin amide quinone (TPPAQ)
which has been synthesized by Tabushi’s group.89 The porphyrin moiety of 108 is
covalently linked to a quinone via an amide linkage. The whole molecule is relatively
rigid due to the partial double bond character of the carbon-heteroatom bond in the amide
group. Compared to TPPAQ, apart from that the quinone was connected to the para-
position instead of the ortho-position, porphyrin moiety of 108 was modified with three

methylpyridinium groups. This hydrophilic property of methyl pyridinium should ensure

138

that the molecule is soluble in water, which serves as the proton source for the

protonation reaction.

SSH

 

103 TPPAQ

II. Results and Discussion

A. Synthesis

The strategy for the synthesis of dyad 108 is analogous to that used in Tabushi’s
group for making TPPAQ. The synthesis of unsymmetrical pophyrins having three
pyridine and one nitro-phenyl groups at the mesa position of the macrocycle was carried
out in acid medium according to the classical Adler-Longo method.90 A propionic acid
solution of 1.75 equivalents of 4-nitrobezaldehyde, 3 equivalents of 4-
pyridinecarboxaldehyde and 4 equivalents of pyrrole was refluxed for 1.5 h in the
presence of acetic anhydride. This mole ratio was chosen because it afforded the best
yield of the desired [5-(4'-nitrophenyl)-10,l5,20-tris(4'-pyridyl)]porphyrin 101. Thus,
101 was obtained in 5% yield after several purification cycles on silica gel to separate the

other porphyrins (tetrapyridylporphyrin, bis-~nitr0phenyl-bis-pyridylporphyrin, tris-

139

nitrophenylpyridyl—porphyrin, tetranitrophenylporphyrin). The amino functional group
was obtained by reducing the nitro group by means of stannous chloride in an acidic
media (6 M HCI). After purification, the 5-(4’-aminophenyl-10,15,20-tris(4’-pyridyl)-
porphyrin 102 was obtained as purple crystals in 80% yield. For the quinone half of the
complex, a commercially available quinone precursor, 2,5-dihydroxybenzoic acid was
employed. The hydroxy groups of 2,5-dihydroxybenzoic acid were protected by treating
with acetic anhydride under acidic conditions to give acetoxy ester 103. This synthetic
step was carried out to overcome the instability of the hydroquinone functional group
during the linking reaction. Attaching this moiety to the porphyrin via an amide linkage
was effected by activating 103 with thionyl chloride to give 1-chlorocarbony-2,5-
diacetoxybenzene 104, which was then reacted with porphyrin 102 to yield porphyrin
dyad 105 in 85% yield (Scheme 17).

The further transformation of 105 is described in Scheme 18. The methylation of
105 was carried out following a literature procedure.91 Porphyrin 105 was refluxed with
a large excess of methyl iodide in chloroform/methanol (90:10) under nitrogen to give
106 in 84% yield. Proton NMR (in DMSO-d6) indicated that all pyridine groups were
methylated to methyl pyridinium groups. The acetoxy groups of 106 were selectively
hydrolyzed in methanolic HCI (apparent pH was 1) following the procedure described by
Tabushi89 to give porphyin hydroquinone 107. Compound 107 was then oxidized by
Pb0292 in methanol at room temperature to give 108 in 71% yield. The formation of
quinone was indicated by the upfield shift of quinone protons compared to hydroquinone.
Porphyrin quinone dyad 108 is photolabile and tends to decompose when exposed to

light. Therefore, the oxidation was carried out in the dark. In actuality, all synthetic

140

N3'-CHO + n +OHC—Q—N02

N
H
l 0113011200011

/
SnClleCI
O No2 -—> N_\ 0 NH2
\
/

  
   

  
 

 

 

 

OH OAC OAc
HOOC (CHaCO)20 HOOC 30% CIOC J
OH OAc OAc
103 104

 

OAc

 

Scheme 17

141

OAc OAc

   

105 106

HCVMeOH

OH

 

Scheme 18

142

operations utilizing porphyrin were done with minimum amount of light. Porphyrin 108
is soluble in water. Since the ET studies will be performed in a buffered solution, it is not
necessary to perform an ion exchange to ensure the presence of a single anion in the

molecule.
B. Preliminary ET studies

Porphyrin 108 shows a good solubility in water, allowing ET experiments to be
carried out in aqueous buffer solution. The photoinduced ET rates from a porphyrin to a
quinone were measured using a fluorescence quenching technique. Fluorescence
lifetimes of 108 and 106 were measured in water at different pH by a single photon
counting technique using a picosecond dye laser. Fluorescence intensity of the quinone-
linked porphyrin 108 was decreased as compared to that of the corresponding reference
compound 106. Based on the fluorescence lifetimes, electron-transfer rates, were
estimated by using equation (5.1):

kET =t‘ —r;c'f (5.1)

where kET is the electron transfer rate, r is the lifetime of the quinone—linked porphyrin

and Tmf is the lifetime of the reference substance.

The charge recombination process was studied by using a nanosecond transient
absorption technique. Spectral changes after the laser flash for 108 were very similar to
those obtained on oxidation of mesa-tetraphenyporphyrins (TPP) to their cationic
radicals."3 Thus, the difference spectrum obtained after laser excitation of 108 was
consistent with the formation of P°+AQ". Rate constants were obtained by analyzing the
decay of this absorption. Figure 24 shows the rate constants for both the forward (CS)

and back (CR) ET measured at different pH.

143

The rate for ET from porphyrin to quinone displays strong pH dependence and the
ET rate increases with the pH of the solvent. These results can be explained by using
PCET theory. Accordingly, the electron transfer from a porphyrin to a quinone is
accompanied by the proton uptake from the solvent (eq. 5.1). This process is competing

with the process that contains no proton uptake (eq. 5.2).
FAQ + H” __> P'+AQ'H (5.1)

PAQ —* P°*AQ" (5.2)

The thermodynamic stability of the quinone product is determined by the pH of
the solvent. At low pH, P°+AQ°H is more stable than P°+AQ", and eq. 5.1 represents the
main pathway for the ET from the porphyrin to the quinone. As we discussed previously,
proton uptake can give rise to extra reorganization energy; thus, the observed ET rate is
slow. At higher pH, P°+AQ" is thermodynamically preferred and thus eq. 5.2 represents
the major pathway for the ET, in which the observed ET is faster because no proton is
involved.

The involvement of proton in the ET reaction is supported by the charge
recombination kinetics. Compared to other porphyrin-quinone systems,94 the back ET is
extraordinary slow and thus results in a long-lived charge separation state. This can be
rat1onalized as a protonation of the semiquinone radical, which traps the electron at the

acceptor and thus forms a stable state.

144

 

 

 

 

1010
109—
O o
,_ 108— O
m 0
\8 10’—
x0
10“—
105—
’ o
104 l l I I l
2 4 6 8 1o 12

Figure 24. pH-dependence of forward ET (0) and back ET rates (0)

14

145

III. Experimental

5-(4-nitrophenvl)-10, 15, 20-tris(4’pvridvlmorphvrin 101

A mixture of 4-nitrobenzaldyde (3 g, 0.020 mol, 1.75 eq) and acetic anhydride (15 ml)
was heated to 110°C in propionic acid (135 ml). To this solution pyridinecarboxaldehyde
(3.2 mL, 0.034 mol, 3 eq) was slowly added followed by pyrrole (3.1 mL, 0.045 mol, 4
eq) and the mixtrue was refluxed for 1.5 h. Most of solvent was removed by distillation
under reduced pressure. The residue was neutralized with 2 M ammonia solution and
collected by filtration. After dring in air, the solid was dissolved in dicholoromethane
and the insoluable residue was filtered off. The solvent was removed from the solution
under vaccum and the resulting residue was purified by column chromatography on silica
gel (dicholoromethane/methanol 96:4). This process was repeated three times to give the
desired compound (0.4 g, 0.6 mmol) in 5.3% yield. UV-visible (CHzClz): A 418; 512;
546; 586; 640 nm. 1H NMR (300 MHz, CDCl3): 8 -2.989 (2H, 5, NH); 8.15 (6H, d, 3, 5-
pyridine); 8.38 (2H, d, 3, 5-(4-nitrophenyl)), 8.81 (2H, d, 2, 6 -(4-nitrophenyl)); 8.87 (6H,
m, B-pyrrole); 9.06 (6H, d, 2, 6-pyridine); MS (CI 706V), m/e = 662, clcd 662.21 for

C41H26N802

5-(4-Aminophenyl)- 10, 15 ,20-tris(4-pyridyl)porphvrinl_02

Stannous chloride dihydrate (0.23 g, 1.0 mol, 8 eq.) was added to porphyrin 101 (70
mg. 0,11 mol) in 6 M hydrochloric acid (6 ml) and the mixture was stirred at room
temperature for 15 h. The mixture was neutralized with 2 M ammonium hydroxide, then

extracted with dichloromethane. The solution was washed with water and the organic

146

layer was dried over sodium sulfate. The solvent was evaporated to dryness and the
residue crystallized from dichloromethane/methanol to give 102 (56 mg, 0.089 mmol) in
80.5% yield. UV-visible (CHzClz): km, 420; 516; 552; 592; 646 mm. 1H NMR (300
MHz, CDCl3): 8 -2.87 (2H, 8, NH), 7.06 (2H, d, 3, 5-(4-aminophenyl)); 7.97 (2H, d, 2, 6
-(4-aminophenyl)); 8.15 (6H, d, 3, 5-pyridine); 8.79 (2H, d, B-pyrrole); 8.83(s, 4H, 13-
pyrrole); 9.01(2H, d, B-pyrrole); 9.05 (6H, d, 2, 6-pyridine); MS (CI 70 eV), m/e = 632,

ClCd 632.24 fOI' C41H23N3

2, 5- Diacetoxybenzoiciid 103

2, 5-Dihydroxybenzoic acid (3.85 g, 25 mole), acetic anhydride (14.5 mL) and sulfuric
acid (0.1 mL) were warmed for 25 minutes on a steam bath and then poured onto 25 g of
ice. The mixture was allowed to stand overnight and the precipitate that formed was
collected by filtration. The product was recrystallized from a mixture of benzene/hexane
to give 4.4 g (74%) of the title compound. mp 117-118 °C; 1H NMR (300 MHz, CDCl3):
8 2.27(3H, s, CH3), 2.30 (3H, s, CH3), 7.10 (1H, d, aromatic), 7.35 (1H, dd, aromatic),

7.8 (1H, d, aromatic); MS (C170 eV) m/e = 238, clcd 238.05 for C1 1H1006

2L5- Diacetovaenzovl Chloride 104

A mixture of 2, 5 diacetoxybenzoic acid 103 (200 mg, 0.84 mmol) and freshly distilled
thionyl chloride (3 ml) was refluxed for 5 h under nitrogen. The solution was allowed to
stand at room temperature for 15 hours and then evaporated to dryness under vacuum to
give 180 mg of 104 (83% yield). mp 93-95 °C; 1H NMR (300 MHz, CDCl3): 2.35 (6H, s,

CH3), 7.18 (1H, d, aromatic), 7.43 (1H, dd, aromatic), 7.98(1H, d, aromatic); MS (CI 70

147

eV), m/e = 256, clcd 256.01 for C. (H905Cl

5-[4’ -(2”,5”-diacetovaenzovl)aminophenyll-10,l5,20-tris(4’-pvridvl)porphvrin 105

Porphyrin 102 (100 mg, 0.16 mmol) in dry dichloromethane (50 ml) and pyridine (0.5
mL) was added to the acid chloride 104 obtained from the previous step. The reaction
mixture was stirred for 1 h under nitrogen. The solution was washed with water three
times and then concentrated by rotary evaporation. The resulting porphyrin was purified
on silica gel (eluting with dichloromethane containing 3% methanol) to give the title
compound (113 mg, 0.13 mmol) in 83% yield. UV-vis: 71m” 418, 513, 546, 589, 645 nm;
lH NMR (300 MHz, CDCl3): 2.40, 2.52 (3H each, s, CH3 of acetoxy), 7.30 (1H, d,
aromatic), 7.36 (1H, dd, aromatic) 7.78 (1H, d, aromatic), 8.06 (2H, d, amide phenyl),
8.18 (6H, m, 3, 5—pyridy1), 8.22 (2H, d, amide phenyl), 8.64 (1H, s, amide H), 8.88 (6H,
m, B-pyrrole), 8.98 (2H, m, [3- pyrrole), 9.06 (6H, m, 2, 6-pyridyl); MS (FAB), m/e

=852.2, clcd 852.28 for C52H36N305

5-[4’ -(2”.5”-dia_1cetovaenzovl)aminophenyl |-10,15,20-tris(4’ -methylp_flidinium)

porphyrin iodide 106

 

A solution containing porphyrin 105 (113 mg, 0.13 mmol), 1:9 ethanol-chloroform (10
ml) and methyl iodide (3 ml) was refluxed under nitrogen overnight. The precipitate was
collected by filtration, washed with chloroform and air dried to give the title compound
(150 mg, 0.12 mmol) in 90% yield. UV-vis: km 423, 521, 556, 584, 648 nm; 1H NMR
(300 MHz, DMSO-d6): 2.38, 2.40 (3H each, s, CH3 of acetoxy), 4.75 (9H, m, CH3 of

pyridinium), 7.42 (1H, d, aromatic), 7.48 (1H, dd, aromatic), 7.66 (1H, d, aromatic), 8.14

148

(2H, m amide phenyl), 8.22 (6H, m, 3, 5-pyridyl), 8.28 (2H, m amide phenyl), 9.00-9.18

(9, m, pyridyl, B-pyrrole, amide H), 9.50 (6H, m, 2, 6-pyridyl).

5-[4’ —(2”,5”-diacetovaenzovl)aminophenvl]-10,15,20-trisfi1’ -methv1pvridinium)-
porphyrin iodide 107

Dry HCl gas was bubbled through a solution of porphyrin 106 (50 mg, 0.039 mmol) in
methanol (10 mL) for 1 min, and the resulting mixture was stirred under nitrogen for 30
min. The solvent was then removed under vacuum to give 30 mg of porphyrin 107.
UV-vis: km,“ 422, 519, 554, 582, 648 nm; 1H NMR (300 MHz, DMSO-d6): 4.70 (9H, m,
CH3 of pyridinium), 6.95 (2H, m, aromatic), 7.48 (1H, m, aromatic), 8.20 (8H, m,
aromatic), 8.28 (2H, m amide phenyl), 9.00-9.18 (9, m, pyridyl, B-pyrrole, amide H),

9.50 (6H, m, 2, 6-pyridyl)

S-M’ -(2”,5”-diacetovaenzovl)aminophenyll-10,15,20-tris(4’ -methvlpvridinium)-
porphyrin 108

Lead dioxide (200 mg) was added to a solution of porphyrin hydroquinone 107 in
methanol (10 mL). The mixture was stirred for 10 min and then filtered through a
cintered filter funnel. The filtrate was collected and the solvent was removed under
vacuum to give 15 mg of 108. UV-vis: Am,“ 424, 520, 554, 582, 647 nm; 1H NMR (300
MHz, DMSO-d6): 4.70 (9H, m, CH3 of pyridinium), 6.78 (1H, d, aromatic), 6.90 (1H, m,
quinone), 7.42 (1H, d, quinone), 8.04 (2H, d, amide phenyl), 8.14 (2H, d, amide phenyl),
8.35 (1H, br, amide H), 8.90 (6H, d, pyridinium), 9.20 (8H, m, b-pyrrole), 9.35 (6H, d,

pyridinium)

149

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H. Koike, M. Ikeuchi, T. Hiyama, Y. Inoue, in Current Research in
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APPENDIX

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