Porphyrins Metal complex formation

It will not be lost on the reader that, while PHOTOFRIN and compounds (3), (5) and (6) contain no metal, they would be expected to be excellent ligands. Are metal complexes useful as PDT photosensitizers Indeed, they are, and may be expected in the future to become more important. The rest of this chapter is about this aspect it will emphasize metal complex formation and properties in relation to PDT. The synthesis of ligands, while of crucial importance, will not usually be treated here in detail, but leading references to relevant synthetic organic chemistry will be provided. The synthesis of porphyrins and related compounds has been considered in several monographs and reviews (porphyrins,46 47 phthalocyanines48). 

The facility of metal complex formation is underscored by the fact that most porphyrin systems with any type of physiological function occur as metal complexes (e.g. Fe in hemoglobins, myoglobins, cytochromes, catalases and peroxidases Mg in chlorophylls and bacteriochlorophylls Co in vitamin B12). 

The need for multiple desolvation of the metal ion in some systems may provide a barrier to complex formation which is reflected by lower formation rates - especially for inflexible macrocycles such as the porphyrins. Because of the high energies involved, multiple desolvation will be unlikely to occur before metal-ion insertion occurs rather, for flexible ligands, solvent loss will follow a stepwise pattern reflecting the successive binding of the donor atoms. However, because of the additional constraints in cyclic systems (relative to open-chain ones), there may be no alternative to simultaneous (multiple) desolvation during the coordination process. 

The adsorption of transition metal complexes by minerals is often followed by reactions which change the coordination environment around the metal ion. Thus in the adsorption of hexaamminechromium(III) and tris(ethylenediamine) chromium(III) by chlorite, illite and kaolinite, XPS showed that hydrolysis reactions occurred, leading to the formation of aqua complexes (67). In a similar manner, dehydration of hexaaraminecobalt(III) and chloropentaamminecobalt(III) adsorbed on montmorillonite led to the formation of cobalt(II) hydroxide and ammonium ions (68), the reaction being conveniently followed by the IR absorbance of the ammonium ions. Demetallation of complexes can also occur, as in the case of dehydration of tin tetra(4-pyridyl) porphyrin adsorbed on Na hectorite (69). The reaction, which was observed using UV-visible and luminescence spectroscopy, was reversible indicating that the Sn(IV) cation and porphyrin anion remained close to one another after destruction of the complex. 

The orthogonal pitching of the mesityl rings (Fig. 1.25) may inhibit formation of p-oxo dimers (likely to inhibit catalytic oxidations) which can be formed by flat porphyrin rings in their metal complexes, e.g. (TPP) ligands [583]. 

Since Fenton s work in the late nineteenth century, the role of transition metals in oxygen chemistry is known, but the formation of oxygen adducts with coordination metal complexes and their importance for O2 activation have been studied much later [1, 97]. The lively interest in ORR catalysis comes from its utmost importance to the development of fuel cells and this justifies that only a few studies have been done with metal complexes in solution most have been devoted to carbon electrodes modified by immobilization of a catalyst. The research for good catalysts that could be efficient substitutes for the expensive platinum naturally moved toward porphyrins. 

Until now, only a few theoretical studies of porphyrin metalation by divalent metal ions in solution have been reported (72,94,95). In the first theoretical work (94,96) on this topic, insertion of Fe2+ and Mg2+ into the porphyrin ring was studied by DFT methods. The authors followed the reaction from the outer-sphere complex formation via stepwise displacement of the solvent molecules until... 

In addition to the above-mentioned reactions, metal complexes catalyze decarboxylation of keto acids, hydrolysis of esters of amino acids, hydrolysis of peptides, hydrolysis of Schiff bases, formation of porphyrins, oxidation of thiols, and so on. However, polymer-metal complexes have not yet been applied to these reactions. 

Early workers appeared to show that electrophilic substitution reactions could not be carried out on porphyrins, and began to question the aromaticity of porphyrins since this classical pre-requisite of aromatic character could not be accomplished. However, they had concentrated on reactions of metal-free systems, and since many electrophilic substitution reactions utilize acidic conditions (nitration, sulfonation), they were actually dealing with the non-nucleophilic porphyrin dication. But, as early as 1929, H. Fischer had realised that diacetylation of deuteroporphyrin-IX (Table 1) had to be carried out on a metal complex, such as the iron (III) derivative chelation with a metal ion which cannot be removed under the acid conditions of the subsequent reaction, effectively eliminates dication formation. A judicious choice of metal complex therefore needs to be made for any particular reaction. For example, though magnesium(II) produces an extremely reactive substrate for electrophilic substitution reactions, it is removed by contact with the mildest of acids and is, consequently, of little use for this purpose. 

Several porphyrin analogues with the pyrrolic nitrogens substituted by heteroatoms have been synthesized, but only the oxa analogues (23 X = O, Y = NH) are reported to form stable metal complexes (Figure 8). 60 Formation of a Zn complex of the thia analogue (23 X = S, Y = NH) requires the presence of a large excess of Zn" ion. An iron complex of dithiaporphyrin (23 X = Y = S) is also known. 

An entirely distinct series of model complexes has been carried out in order to show that metal porphyrins will actually bind to the type of substrate with which P-450 interacts. Hill, Macfarlane, Mann, and Williams (51) have studied molecular complex formation between such molecules as quinones and sterols and several metal porphyrins. The complexes between some of the porphyrins and sterols are remarkable strong. At the same time they have devised NMR methods for the elucidation of the structures of these complexes. 

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