Chapter 1

PORPHYRINS AND METALLOPORPHYRINS

1.1. Introduction

Porphyrins are one of the vital chemical units essential for several life

processes on the earth. Many biological molecules function with prosthetic

groups essentially made of these units. Chlorophylls of chloroplasts which

drive photosynthesis, heme as a component of hemoglobin that transports

oxygen to animal tissues and as the central unit of myoglobin ensures the

storage of oxygen - all these have active sites essentially made of porphyrin

core'". Over the years, a great deal of concerted efforts have brought to light

substantial understanding of the structure-function relationship in these natural

porphyrins"'O

A large variety of synthetic porphyrins and their metalloderivatives were

made over the years to study the porphyrin based natural systems. The search

for anti-cancer drugs, useful catalysts, semiconductors and superconductors,

electronic materials with novel properties has also made this synthetic

porphyrin chemistry a very actively probed one by chemists, biologists and

physicists alike. The synthetic meso-substituted porphyrins offer a great

advantage to study the physical and chemical properties of the porphyrin

nucleus quantitatively by a judicious choice of the substituents that may be

attached on the periphery. Metalloporphyrins are widely and intensely

investigated in the area of catalysis and also as models and mimics of enzymes

l i e catalase, peroxidases, P450 cytochromes or as transmembrane electron 11-13 transport agents . They have also been used as NMR image enhancement

agents14, Nonlinear optical materials" and DNA-binding or cleavage agent1" . 17 . Currently there is interest in using chelated radioactiv

diagnostic imaging and therapeutic agents. In that con

excellent compounds because of their extremely high s

many metal ions.

1.2. The Porphyrin System

Porphyrins are basically cyclic tetrapyrrole derivatives with a highly

delocalised planar ?r-framework having a core structure 1. They can exist in

varied forms by having different peripheral substituents at all the eight pyrrole

P-carbon atom and the four meso-carbon centres and also by undergoing

certain structural variations.

Porphyrin is an 18-n: electron system and hence exhibits aromaticity18.

The simplest porphyrin is known as porphine which is the H-analogue (R1 -

R12 = H) of 1. Besides many synthetic and naturally occurring ones with the

core structure mentioned above, there are many biologically active systems

which also have porphyrin-like structures which are given in 2-7.

Porphin Chlorin Phorbin

2 3 4

Bacteriochlorin Porphyrazine Phthalocyanine

5 6 7

The prophyrin ring provides a vacant site at its center, ideally suited for

metal incorporation. The NH protons inside the ring of porphyrins possess

acidic character and hence can get deprotonated to give porphyrinato ions.

These dianion species with their electronically sensitive planar n-framework

and central cavity with more or less rigid size exhibit remarkable ligation

characteristic towards metal ions. Thus derivatives of porphyrins with almost

all metals and semimetals have been synthesisedl. A crucial factor to form

stable metalloporphyrins seems to be the compatibility of porphyrin ring size

with the ionic radii of the metal cations". Hence stable complexes generally

result when these two sizes match while their instability tends to increase when

the size of the cation is too big or too small with very few exceptions. The

porphyrinato dianion is ideally suited to act as a tetradenate ligand with metal

ions2'. Thus the minimum coordination number of the metal ion possible in a

metalloporphyrin is four. A size matching divalent metal ion would give

neutral complex, while a higher valent cation would carry with it balancing

anion@) mostly covalently bound with the metal, in addition to the

porphyrinato ion. f i e normal coordination geometry around the metal ion in

the former species would be square planar, while in the latter case the

coordination geometry would be square pyramidal. Coordination number

greater than four is also possible. The two ligands of the six coordinate

metalloporphyrins are found on the opposite sides of the porphyrinato plane

yielding complexes with tetragonal or octahedral geometries20. Ability to

exhibit variable oxidation states of metals in their metalloporphyrins is another

important feature in this class of compounds. They are also capable of

stabilizing metal ions in their unusual oxidation states, which have resulted in

extensive studies revealing interesting chemistry.

The nature of bonding between a central metal and the porphyrin ligand

is found to be originating essentially from the following two types of primary

interactions: a-coordination of nitrogen lone pairs directed towards the central

metal atoms and n-interaction of metal pn or dn orbitals with nitrogen-based n

orbitals2'. The appropriate symmetry-adapted linear combinations of

prophyrin-ligand orbitals involved in the bonding with metal orbitals are shown

in 8.

(b)

8

The symmetry adapted linear combi~tion ofpotphyin-Iigand orbitals involved in the

bonding with metal obitals (a) me suitable for einteraclonsand (6) for z-interactions

In the a-system the prophyrin is clearly a donor to the metal while in the

x-system porphyrin has the appropriate orbitals to act both as a n-donor and as

a n-acceptor.

The versatile characteristics of the ubiquitous porphyrin molecules can

be attributed largely to the extensively delocalised 7r-system which is

electronically very sensitive and tunable. A knowledge on all such crucial

factors is often necessary before one tries to design and develop the ideal

molecular system for any specific purpose. The studies on porphyrins so far

indicate the following factors to be very significant.

(i) The nature of peripheral substituents has great ability to tune the

electronic levels of porphyrin and their metalloderivatives.

(ii) The type of central metal ion has a very pronounced effect on the

electronic property of the porphyrins. The nature of interaction between

the metal ion and the porphyrinato moiety is such that both the species

mutually influence their electronic levels.

(iii) There is generally a thermodynamic drive for square planar complexes

to add on axial ligands, if available. Most of the metal(II) porphyrin

complexes thus tend to take octahedral geometry when exposed to

coordinating species. Such a change in geometry affects both the metal

electronic levels and porphyrinato orbital energies. Five coordinated

species for metal(1I) porphyrins with one neutral axial ligand are

generally unstable but have been suggested to occur as an intermediate

in solution state. Electronically, five coordinate species are different

from six coordinate complexes and are more reactive due to

coordinative unsaturation.

(iv) In most of the biological systems, the porphyrin moiety is often covered

and buried at specific sites by the long chain of the protein residues.

This steric crowding of protein chain around it can cause some tilt or

puckering in the planar n-framework of the metalloporphyrin. Such a

distortion then would cause a noticeable decrement in the extent of

overlap of certain n-molecular orbitals of the macrocycle with symmetry

matching metal orbitals. The net effect of this would be an enforced

strain on the molecule. The tendency of these entatic species would be to

release the strain that is supposed to be the driving force for these

species to behave as biological catalysts.

1.3. Electronic Properties of Porphyrins and Metalloporphyrins

The most useful spectroscopic technique for the study of porphyrin and

their metalloderivatives is the electronic absorption spectroscopy. As the

spectral absorptions are found to be sensitive to the nature of porphyrins and its

surroundings, vital information could be obtained on the nature of chemical

environment in which they exist and on the role these molecules play in key

biological functions they take part, all by just monitoring the electronic spectra

in respective conditions. Since the present study deals with some aspects of

aggregation characteristics of porphyrins and environment effects on their

electronic spectra provide a vital tool to study them. A brief description on the

origin of the spectra of the porphyrins and their metalloderivatives are given

below.

The electronic heart of a porphyrin is the inner 16-membered ring with

18-x electrons. The ring is structured with basic fourfold symmetry, including

four nitrogen atoms directed towards the center. This electronic heart is

responsible for the unique porphyrin-type optical spectra, which are then

perturbed to a greater or lesser extent by various chemical modifications to the

basic structure.

Porphyrin and its metal derivatives are of considerable spectroscopic

interest because of their simplicity and uniqueness. The optical absorptions of

porphyrin are determined essentially by the nelectrons on the porphyrin ring,

with only minor perturbation from the electrons of the central substituents.

The optical absorption spectra is ati important spectral phenomenon to

distinguish between the free-base porphyrins and their metalloderivatives. The

spectrum changes from four-banded to a two-banded spectrum on metallation.

This dramatic effect is attributed to the enhancing of the DZh symmetry of the

free-base porphyrin to D4h on metal~ation~~.

Majority of metal-free porphyrins shows very characteristic absorption,

which consist of two sets of bands in the ranges of 400-450 nm and 550-700

nm. The fust sets of bands are called the B band or Soret band (strongly

allowed) and the lower energy set are the Q bands (quasi-allowed). A typical

spectrum of a regular porphyrin along with one of its metalloporphyrin is given

in Fig.l.1.

400 600 wavelenath (nm)

Fig.1 .l . Electronic absorption spectra of (a) free-base porphyrin and (b) its metalloderivative

The Q bands of free-base porphyrins are a set of four absorptions arising

from HOMO to n* transition. Of these, the first set of two lines is X-

component of Q while the second set is its y-component. Both these Q, and Q,

components are composed of two types of vibrational excitations too, the lower

energy one being Q(0,O) and the higher energy one Q(1,O). Thus the four lines

in the set are Q,(0,0), Q,(1,0), QJ0,O) and Q,(1,0) in the increasing order of

energy.

On metallation, the spectrum shows an intense B (Soret) band at -420

nm and two weaker Q bands at - 550-600 nmlsP. These spectral absorptions

arise from n-z* transitions of the aromatic porphyrin ligand.

The widely accepted model to fit this spectrum, the four-orbital model,

treats the porphyrin as a cyclic polyene and emphasizes the transition between

the two highest filled bonding molecular orbital levels, a,,, azU and the lowest

empty doubly degenerate antibonding molecular orbital levels eg*. The

allowed transitions, a,, -+ eg* and azU -+ eg* are assumed to be degenerate in

energy. As a consequence, the states undergo configuration interaction and

give rise to new states. The resulting spectrum shows a highenergy band B in

which the transition dipoles add and a low-energy band Q in which the

transition dipoles cancel. The two Q bands are vibronic components of the

same tran~ition*~.

1.4. Types of Porphyrins

There are a variety of porphyrins that are of special significance.

Described below in brief are some of them.

(a) Protoporphyrin

Protoporphyrin (9) contains four methyl groups, two vinyl groups and

two propionic acid groups on its periphery. Fifteen different isomeric

protoporphyrins differing in the sequence of substitution of the above groups in

eight available positions are possible. Hemin is the prosthetic group of

hemoglobin, myoglobin, peroxidase, P-type cytochromes, catalase, tryptophan

pyrrolase, cytochrome P450 and many other proteins. Synthesis of porphyrins

derived from those found in animal materials invariably involves hemin or

protoporphyrin as starting material.

Protoporphyrin dimethyl ester is most easily obtained from hemin by

iron removal and esterification. The original Grinstein procedure that

accomplishes both operations simultaneously involves passage of gaseous HCI

through a methanolic solution of heminz5.

0) De@teropo~vrin Deuterohemin (10) was a key intermediate in Fischer's total synthesis of

hemin. A Friedel-Crafts acylation of deuterohemin folowed by reduction and 26.27 dehydration gave protohemin . Because they have two free P-positions,

deuteroporphyrin and deuterohemin have been used as starting materials in the

synthesis of several porphyrins in which the vinyl groups of protoporphyrin are

replaced by other functionalities. The 2,4dibromo, diacetyl, dipropionyl and

dihydroxymethyl derivatives are all synthesised directly from

deuteroporphyrin. Purification of deuterohemin was done using

deuteroporphyrin in Caughey's methodz8. The iron chelate is obtained by

reinsertion of iron into deuteroporphyrin dimethylester. Deuteroporphyrin-free

10

acid may be obtained from the dimethyl ester by hydrolysis, or from purified

deuterohemin free acid by iron removal.

(c) Hematoporphyrin

Hematoporphyrin (11) was the fmt porphyrin isolated from natural

materials. It was prepared by Thudichum in 1867 by the sulfuric acid treatment

of blood. Hematoporphyrin can also be prepared by the treatment of hemin

with HBr in acetic acid. The HBr adduct is then decomposed with water to

give hematoporphyrin. Hematoporphyrin is by far the most labile natural

porphyrins commonly used in the laboratory.

(d) Mesoporphyrin

Mesoporphyrin (12) is used in biological and chemical studies especially

where the liability of the vinyl groups of protoporphyrin is a factor. The

classical method of mesoporphyrin synthesis was HI reduction of protohemin29. -++& \ / ce) K 7 - - y . w .

\ 7 y //-, h!, OOH <.: .- - - - -4-

Better result was obtained by the catalytic reduction over PdO of protohemin,

protoporphyrin or protoporphyrin dimethyl ester in formic acid at elevated

temperature. The most convenient method for obtaining large amount of

mesoporphyrin was developed by caughey3'. In this method hydrogen was

bubbled through a formic acid solution of hemin over PdO.

(e) Diace@ldtwteroporphyrin

This prophyrin (13) possesses electron withdrawing acetyl groups in the

2- and 4-positions. Fischer's classical method is now used for the synthesis of

diacetyldeuteroporphyrin. Crude deuterohemin was dissolved in acetic

anhydride at 0°C followed by the addition of anhydrous SnCb under constant

stirring. Longer reaction times result in substantial decomposition, and shorter

times give substantial mount of the monoacetylated product. The solution is

further acidified using 0.1N HCI and thoroughly stirred to avoid acetic

anhydride formation. The crude diacetyldeuterohemin is isolated by suction

filtration.

Diformyldeuteroporphyrin (14) with two strongly electron-withdrawing

formyl groups has been used in the studies of the relationship of heme structure

to heme protein function3'. Fischer's method, alkylation of deuterohemin with

dichloromethyl methyl ether in the presence of SnBr4 followed by hydrolysis,

gives a mixture of products including the monoformyl compounds.

C-type cytochromes (15) contains a prosthetic group, a covalent bound

hemin, that can be regarded as been formed by the addition of two cystane

sulfhydryls across the double bonds of protoheme. Treatment of cytochrome C

with silver or mercury salts result in the formation of optically active

hematoporphyrin. Acid hydrolysis of horse heart cytochrome C results in the

formation of a homogenous amphoteric porphyrin fraction, which has been 32-34 shown to be porphyrin C .

1.5. Porphyrins in Life Chemistry

Metal complexes of porphyrins and related compounds are important

prosthetic groups that assemble to form a wide variety of proteins and enzymes

working as redox and rearrangement catalysts3'. The nature being a master

designer, has chosen and retained the best choice of molecular assemblies in

living systems to cany out very specifically the functions they are intended for

and also to achieve them with the maximum efficiency.

A large number of naturally occurring porphyrin have been isolated and

characterized. Of these protoporphyrins are the most abundant and widely

characterized ones. It is found in hemoglobin, myoglobin, heme enzymes and

most of the cytochromes5.

The biological and chemical importance of metalloporphyrins has

brought to focus intense interest in the nature of the metal ligand linkages in

such complexes as well as all the physicochemical properties of the

macrocycles. The macrocycle has the ability to function as a reservoir of

electrons and control the reactivity at the axial position of metal, which usually

serves as a catalytic site in heme enzyme. Because of their ubiquitousness and

the variety of their natural functions, heme proteins have been investigated on

multi- and interdisciplinary levels. These proteins all containing an iron

porphyrin as the prosthetic group, are responsible for oxygen transport and

storage (hemoglobin and myoglobin)36, electron transport (cytochrome~)~~,

oxygen reduction (cytochrome o x i d a ~ e ) ~ ~ , hydrogen peroxide utilization and

destruction (peroxidases and cata~ases)~', and hydrocarbon oxidation

(cytochrome, p.450)~~.

Also the various functions of heme proteins in the transport, storage and

reactions with dioxygen are made possible by different and selective

interactions of diverse proteins with the heme groups'0. These differences are

brought about largely by the axial ligands provided by ancillary groups of the

protein and from the nature of the pockets on either side of the porphyrin.

Important porphyrin based natural systems are the hemoglobin, myoglobin,

chlorophyll, heme enzymes and the cytochromes.

1.5.1. Hemoglobin and myoglobin

Hemoglobin and myoglobin are high molecular weight protein systems

containing iron(I1) protoporphyrin IX units. They are responsible for oxygen

transport and storage in higher animals9. Hemoglobin transport dioxygen from

its source to the site of use inside the muscle cells. There the oxygen is

transferred to myoglobin for use in respiration. Myoglobin which is responsible

for storing oxygen in cells, has high affmity for the dioxygen even at low

partial pressure but in lungs, hemoglobin takes up high amount of oxygen at

high partial pressure. This special property of hemoglobin is attributed tothe

'cooperative effect" caused by the decrement in size of ~ e ~ ' in central hole due 40,41

to spin change (from high spin to low spin) on dioxygen complexation .

The iron in hemoglobin and myoglobin is in the ferrous state and has to

have an N-base (histidine) coordinated to the metal from one of the sides of the

plane to have dioxygen bound at the vacant sixth coordination site. The

oxidized form of iron, ie. ferric state, called metmyoglobin and methemoglobin

will not bind oxygen. The free heme is immediately oxidized in the presence of

oxygen and water and thus renders useless for Oz transport.

Myoglobin exhibits greater affimity of O2 than hemoglobin and it is

largely converted to oxyrnyoglobin even at low O2 concentration in order to

effect the transport of O2 at the cell9. Upon the oxygenation of hemoglobin, two

of the heme groups move about 100 pm towards each other while two others

separate by about 700 pm due to the action of protein envelope. The net result

of this combined movement is that hemoglobin can exhibit relatively low

affmity for binding the f i t one or two oxygen molecules. But once they are

bound, the binding of subsequent O2 molecule is greatly enhanced. Conversely

the loss of one oxygen molecule from fully oxygenated hemoglobin causes the

rest to dissociate more readily when the oxygen pressure is decreased42.

1.5.2. Chlorophyll

Chlorophyll is the green colouring matter of leaves and green stems, and

its presence is essential for photosynthesis. In green plants it is the chlorophyll

which absorbs the light energy. Chlorophyll is basically magnesium derivative

of porphyrins and some slight structural changes in porphyrin moiety results in

different classes of chlorophyll with slight difference in photocatalytic

/ - properties5. All of the chlorophylls absorb light very intensely, particularly at

relatively long wavelength regions43. The light energy absorbed by a

chlorophyll molecule become delocalised and spread throughout the entire

electronic structure of the excited molecule.

The photosynthetic pigments in the chloroplasts of plants consists of two

functional units namely photosystem I and photosystem 1 1 ~ ~ . Photosystem I

contains chlorophyll, p-carotene and a single molecule of P-700, a specialised

chlorophyll a which serves as an energy trap. Photosystem II has a

characteristic reactive centre namely Pa80 a specialized chlorophyll-protein

complex. Photosystem I absorbs light at longer wavelength. Photosystem I1 is

activated by shorter wavelength, ie. 670 nm and below and it is responsible for

oxygen evolution.

Both the photosystems contain chlorophyll a and chlorophyll b. In

photosystem I, the ratio of chlorophyll a to chlorophyll b is higher than in

photosystem 11'. These two photosystems must cooperate to yield maximum

result in photosynthesis.

Enzymes are biological catalysts that govern, initiate and control

biological reactivity important for the life processes. They are produced by the

living organism and are usually present in only very small amounts in the

various cells. All known enzymes are proteins and some contain non-protein

moieties termed prosthetic groups that are essential for the manifestation of

catalytic a c t i ~ i t i e s ~ ' ~ ~ . In several natural enzymes, metalloporphyrins constitute

these prosthetic groups, some of which are discussed in brief here.

There are various enzymatic reactions in which one or both atoms of 4

are directly inserted into the organic substrate molecule to yield hydroxyl

groups. Enzymes catalyzing such reactions are called oxygenase, of which

there are two classes - the dioxygenase catalyzes insertion of both atoms of the

0 2 molecules into the organic substrate, whereas the monooxygenase inserts

only one4.

The most important monooxygenase is cytochrome P-450 found in the

microsomes of liver cells4'. Cytochrome P-450 contains protoheme. The CO

derivative of its reduced form absorbs maximally at 450 nm, hence the name

cytochrom P-450. During the enzyme reaction the ferric P-450 first combines

with a substrate followed by a oneelectron reduction to form a ferrous P-450

substrate complex. The reduced Fe(II) form of P-450 reacts with molecular O2

in such a way that one of the 0-atoms is reduced to water and the other is

introduced into the organic substrate.

Cytochrome P-450 enzymes catalyze hydroxylation of many different

k i d s of substrates including steroids, fatty acids, certain amino acids etc and

thus making them more water-soluble. They also promote hydroxylation of

various drugs.

1.5.3.2. Peroxidases and Catalase

Peroxidases are enzymes catalyzing the oxidation of a variety of organic

and inorganic compounds. Peroxidases obtained from plants contain hemine

groups. The different types of peroxidases are horseradish peroxidase, mylo

peroxidase, chloroperoxidase etcB.

Catalase is also a heme enzyme which catalyze the dismutation of H202

generated during various life processes. Catalase is made up of four identical

sub-units each containing one heme group. The axial metal sites appear to be

occupied by water and an amino acid residue.

1.5.4. The Cyt@chromes

The cytochromes are electron transferring proteins, containing iron

porphyrin, found in aerobic cells. Some cytochromes found in endoplasmic

reticulam, play a role in specialized hydroxylation reactions36. All cytochromes

undergo reversible Few-Fe(II) valency changes during their catalytic cycles.

In almost all the cytochromes both the fifth and sixth positions of the iron are

occupied by the R groups of specific amino acid residue of the proteins46.

Therefore, these cytochromes cannot bind with ligands like 4, CO or C N . An

important exception is cytochrome oxidase that normally binds O2 in its

biological function.

The iron protoporphyrin group of cytochrome c is covalently linked to

the protein by thioether bridges between the prophyrin ring and two cysteine

residue in the peptide chain whereas in other cytochromes the porphyrin ring is

non-covalently bound. Cytochrome c is the only common heme moiety in

which the heme is bound to the protein by a covalent linkage.

1.6 Applications of porphyrins and metalloporphyrins

Porphyrins and related macrocycles provide an extremely versatile

synthetic base for a variety of material applications. The broadly defmed

porphyrin research area is one of the most exciting, stimulating and rewarding

for scientists in the filed of chemistry, physics, biology and medicine. The

beautifully constructed porphyrinoid ligand, perfected over the course of

evolution, provides the chromophore for a multitude of iron, magnesium, cobalt

and nickel complexes which are primary metabolites and without which life

itself could not be maintained. The field is spreading rapidly in every direction

across the whole spectrum4'.

Diverse applications of porphyrins and metalloporphyrins to materials

chemistry have been developed over the past decade, both for their optical

properties and their applications as sensors. Notably, porphyrins and

metalloporphyrins have found applications as field-responsive materials,

particularly for optoelectronic applications, including mesomorphic materials

- and optical-limiting coatings. For example, the facile substitution of the

periphery of various porphyrins has generated a series of unusual liquid

crystalline materials. The porphyrin ligand serves as a platform on which one

can erect desirable molecular and materials properties. The nonlinear optical

properties of these materials are of special interest, in part for energy transfer

with molecular control, and in part for potential application in optical

communications, data storage and electrooptical signal processing. The

stability of mono- and di-cation porphyrin x-radicals makes these systems

especially interesting for photoionization processes.

Porphyrins and metalloporphyrins can also be used as nonlinear optical

materials. They have desirable properties for use in optoelectronics. They have

greater thermal stability and their extended lrconjugated macrocycle ring give

large nonlinear optical effects and subtle variation in their physical properties

can be made easily through chemical modification of their periphery48-i4. They

also play key roles in adsorbing light energy over a wide spectral range and

converting it into the highly directional transfer of electrons5*". It is a

marvelous but highly complex process that has inspired considerable interest in

the synthesis of porphyrh arrays. A biomimetic approach to the photosynthetic

apparatus may also lead to applications of similar systems as optoelectronic

devices.

Because of their inherent stability, unique optical properties, and

synthetic versatility, porphyrins and metalloporphyrins are excellent candidates

for a variety of sensing-materials applications. Research in this area has

focussed on incorporation of synthetic porphyrins and metalloporphyrins into a

variety of material matrices, such as polymers, glasses and films6'. The unique

spectral characteristics and synthetic versatility of porphyrins allow a variety of

sensing applications. They are also used in the detection of organic vapours and

ionic species in solution.

Photochemical reduction of water utilizes only a limited portion of sun's

ray. Porphyrins, whose absorption spectra wver an appreciable portion of the

spectrum of sunlight, are of great interest in this respect. Also

metalloporphyrins exhibit very high photochemical stability6'. Large attempts

are also made to utilize the photochemical properties of metalloporphyrins in

organic synthesis. For eg., it was found that irradiation by a W-visible light to

a solution of Fe(TDCPP)OH in 02-satuntted cyclohexane led to progressive

formation of cyclohexane6'. The author proposed a mechanism for this reaction

in which the fmt step is a photodissociation of the Fe(II1)-OH bond of the

catalyst leading to (TDCPP)Fe(II) and OH followed by H-atom abstraction of

cyclohexane by OH as represented in Scheme 1.

Scheme 1 Mechanism for the oxidation of alkanes to ketones by O2 catalyed by photoactivated Fe(TDCPP)OH

Metalloporphyrins of aluminium, zinc, manganese, cobalt and rhodium

complexes have been demonstrated to serve as excellent initiators for

controlled anionic and free radical polymerizations6466. The discovery of these

metalloporphyrins-based initiators has led to significant contributions to the

progress of precision macromolecular synthesis via "living polymerization"

(ie., growth pattern of the macromolecule can be viewed as analogous to the 67-69 growth of a biological organism) .

The worldwide approval of Photofib [a purified version of

Hernatoporphyrin derivative (HpD); a complex mixture of dimers and

oligomers in which porphyrin units are joined by ether, ester and carbon-carbon

bonds] for the treatment of various types of cancers has created enormous

70-71 interest among physicians, chemists, biologists and physicists . During the

early and mid 1970s, several groups including Diamond et. aL7', Kelly and

~ n e l l ~ ~ , and Dougherty et. a~. '~ , realized that together HpD and light (Photo

dynamic therapy) had a, potential capability for tumor destruction. This is now

one of the accepted modalities for the treatment of ~ a n c e r ' ~ . ~ ~ . In addition to its

use for cancer treatment, Photo dynamic therapy has also shown a potential for

applications in other areas: treatment of aged-related macular degeneration,

Psoriasis, bone marrow purging, arthritis and purification of blood infected

with various viruses inchding HIv4'. At present, all the photosensitizers in

clinical trials are based on tetrapyrroles (porphyrins, chlorins, bacteriochlorins

and pthalocynanines), and it seems that porphyrin in general will show

continued interest in the exiting area of photodynamic therapy.

1.7 References

1. J.W. Buchler, "The Porphyrins", D. Dolphin (Ed.), Academic, New York, Vol. 1, Part A, Structure and Synthesis (1978).

2. D. Ostfeld, Tsutsui, Acc. Chem. Res., 7, 52 (1974).

3. 3. O.A. Golubchikov and B.D. Berezin, Russ. Chem. Rev., 55(8), 1361 (1986).

4. 0. Hayashi, "The Enzymes", P. Boyer, H. Lardy, K. Myrback (Eds.), Academic Press, New York, Vo1.8 (1963).

5. A.L. Lehinger, "Biochemistry", Kalyani Publishers, New Delhi (1978).

6. E.L. Smith, R.L. Hill, I.R. Lehman, R.J. Lef Kowitz, P. Handler, A. White. "Principles of Biochemistry- General Aspects", McGraw-Hill Inc., Singapore (1983).

t - 7. T.S. Mashiko, "Comprehensive Coordination Chemistry", Geoffery and Wilkinson (Eds.), Vo1.2, Pergamon Press, Oxford (1987).

8. G.I. Likhtenshtein, "Chemical Physics of Redox Metalloenzyme Catalysis", Springer-Verlag, Berlin, (1988).

9. J.E. Huheey, E.A. Keiter, R.L. Keiter, "Inorganic Chemistry - Principles of Structure and Reactivity", Harper Collins College Publishers, New York

b (1993).

10. J.P. Collman, Inorg. C:hem., 36,5145 (1997).

1l.O.A. Golubchikov, B.D. Berezin, Russ. Chem., Rev., 55(8), 768 (1986).

12. B. Meunier, Chem. Rev., 92, 141 1 (1992).

13. V.V. Borovkov, R.P. Evstigneeva, L.N. Strekova, E.I. Fillippovich, Russ. Chem. Rev., 58(6), 602 (1989).

14. K.E. Keller, N. Foster, Inorg. Chem., 31, 1353 (1992).

15. K.S. Suslick, C.T. Chen, G.R. Meredith, L.T. Cheng, J. Am. Chem. Soc., 114,6928 (1992).

16.L.G. Marzilli, New J. Chem., 14,409 (1990).

17.N.E. Mukundan, G. Petho, D.W. Dixon, L.G. Marzilli, Inorg. Chem., 34, 3677 (1995).

18.M. Gouterman, "The Porphyrins", D. Dolphin (Ed.) Academic New York, Vol.111, Part A, Physical Chemistry (1978).

19. J.W. Buchler, "Porphyrins and Metalloporphyrins", K.M. Smith (Ed.), Elsevier (1 975).

20. W.R Scheidt, Accounts of Chemical Research, 10,339 (1977).

21.K. Tatsurni, R. Hoffinann, J. Am. Chem. Soc., 103,3328 (1981).

22.M. Gouterman, J. C'hem. Phys., 30,1139 (1959).

23.L.J. Boucher, Coord. Chem. Rev., 7,289 (1972).

24.M. Zerner, M. Goutennan, Theoret. Chim. Acta, 4,44 (1966).

25. M. Grinstein, J. Biol. Chem., 167,515 (1947).

26.H. Fischer, K. Zeile,, Justus Liebigs Ann. Chem., 468,98 (1929).

27.H. Fischer and R. Muller, Hoppe-Scylers, Z. Physiol. Chem., 142, 155 (1925).

28. W.S. Caughey, J.O.Alben, W.Y.Fujimoto, J.L. York, J. Org. Chem., 31, 2631 (1966).

29. S. Schwartz, M.H. Berg, I. Bossenmaier, H. Dinsmore, Methods Biochem. Anal., 8,221 (1960).

30. W.S.Caughey, W.Y. FujimotoJ. Bearden, T.H. Moss, Biochemistry, 5, 1255 (1966).

31.T.Asakura, M. Sono, J. Biol. Chem., 249,7089 (1974).

32.R Hill, D. Keilin, Prw. R. Soc. London, Ser. B., 107,286 (1930).

33.H. Theorell, Enzymologia, 6,88 (1939).

34.H. Theorell, K. Akeson, J. Am. Chem. Soc., 63, 1804 (1941).

35. R.A. Pasternack, A. Ghetto, P. Pagano, E.J. Gibbs, J. Am. Chem. Soc. 113,7799 (1991).

36.F.S. Mathews, Prog. Biophys. Mol. Biol., 45, 1 (1985).

37. Y. Hatefi, Ann. Rev. Biochem., 54,1015 (1985).

38. J.E. Frew, P. Jones, Adv. Inorg. Bioinorg. Mech., 3, 175 (1984).

39.R.T. Murray, M.T. Fischer, P.G. Debrunner, S.G. Sligar, Top. Mol. Struct. Biol., 6 (Metalloproteins, Pt.l), 157 (1985).

40. J.L. Hoard, "Hemes and Hemoproteins", B.Chance (Ed.), Academic Press, New York (1966).

41. W.R. Scheidt, C.A. Reed, Chem. Rev., 81,543 (1981).

42.M.S. Perutz, Nature, 228,726 (1970).

43.H.H. Seliger, W.D. McElory, Light; Physical and Biological Action, Academic Press, New York, 1965.

44.K. Saner, Annu. Rev. Phy. Chem., 30, 155 (1979).

45. K.E. White, M.J. Coon, Annu. Rev. Biochem., 49,356 (1980).

46.T. Takano, B.L. Trus, N. Mandel, G. Mandel, O.B. Kallai, R Swanson, R.F. Dickerson, J. Biol. Chem., 252,776 (1977).

47. J.-H. Chou, M.E. Kosal, H.S. Nalwa, N.A. Rakow, K.S. Suslick, "The Porphyrin Handbook", K.M. Kadish, K.M. Smith, R. Guillard (Eds.) Vol. 3, Academic Press, New York (2000).

48. H.S. Nalwa, "Nonlinear Optics in Organic Molecular and Polymeric Materials", H.S. Nalwa, S. Miyata (Eds.) CRC Press, Boca Raton, FL, 61 1- 797 (1997).

49. H.S. Nalwa, T. Watanabe, S. Miyata, "Nonlinear Optics in Organic Molecular and Polymeric Materials", H.S. Nalwa, S. Miyata (Eds.) CRC Press, Boca Raton, FL, 61 1-797 (1997).

50. H.S. Nalwa, "Handbook of Organic Conductive Molecules and Polymers", H.S. Nalwa (Ed.) John Wiley & Sons, Chichester, 261-363 & Vol. 1-4 (1997).

51. H.S. Nalwa, J.S. Shirk, "Pthalocyanines: Properties and Applications", C.C. Leznoff, A.B.P. Lever (Eds.)Vol. 4,79-118 (1996).

52.H.S. Nalwa, Adv. Mater., 5,341 (1993).

53.H.S. Nalwa, Appl. Organometal. Chem., 5,349 (1991).

54. D.S. Chemla, J. Zyss, "Nonlinear Optical Properties of Organic Molecules and Crystals", Academic Press, Orlando (1987).

55.G.W. Robison, Brookhaven Symp. Biol., 19, 16 (1967).

56. R.H. Pearlstein, New Compr. Biochem., 15,299 (1987).

57.G.R. Fleming, J.-L. Martin, J. Breton, Nature, 333, 190 (1988).

58.M.L. Paddock, S.H. Rongey, G. Feher, M.Y. Okamura, Proc. Natl. Acad. Sci., USA, 86 (1989).

59.G. Feher, J.P. Allen, M.Y. Okamura, D.C. Rees, Nature, 339, 11 1 (1989).

60.D. Holten, C. Kirmarier, Photosynth. 13,225 (1987).

61.A.E. Baron, J.D.S. Danielson, M. Gouterrnan, J.R. Wan, J.B. Callis, Rev. Sci. Instrum., 64, 3394 (1993).

62.0.A. Golubchikov, B.D. Berezin, Russ. Chem. Rev., 55,768 (1986).

63.D. Mansuy, Coord. Chem. Rev., 125, 129 (1993).

64.T. Aida, S. Inoue, Acc:. Chem. Res., 29.39 (1996).

65.S. Inoue, T. Aida, Chemtech, 24,28 (1994).

66. B.B. Wayland, S. Mukerjee, G. Posmik, D.C. Woska, L. Basickes, A.A.M. Gridnev, S.D. Ittel, ,4CS Sympo. Ser. 686,305 (1998).

67.M. Szwarc, M. Levy, K. Milkfish, J. Am. Chem. Soc., 78,2656 (1956).

68.T. Aida, Prog. Polym. Sci., 18,469 (1994).

69. S. Inoue, T. Aida, "New Method for Polymer Synthesis", W.J. Mijs (Ed.), Plenum, New York, 33 (1992)

70. J.S. McCaughan Jr., J. Clin. Laser Med. Surg., 14,223 (1996).

71.H. Kato, T. Okunaka, H. Shimatani, J. Clin. Laser Med. Surg., 14,235 (1996).

72.1. Diamond, S.G. Graneli, A.F. McDonagh, C.B. Wilson, S.L. Nielsen, Lancet, 2, 1 175 (1972).,

73.J.F. Kelly, M.E. Snell, J. Urol., 155,150 (1976).

74.T.J. Dougherty, G.B. Grindley, R. Fiel, K.R Weishaupt, D.G Boyle, J. Natl. Cancer. Inst., 55, 115 ( 1975).

75. T.J. Dougherty, J. Clin. Laser Med. Surg., 14,219 (1996).

76.FDA Approval for Photofiin for Early NSCLC, Oncology Times (1998).