Radical mechanisms, porphyrin cation

Electron Hopping and Porphyrin Cation Radical Mechanisms... 

Cytochrome P-450, which is the most extensively studied of the monooxygenase proteins, has a heme-iron active center with an axial thiol ligand (a cysteine residue). However, most chemical model investigations use simple iron(III) porphyrins without thiolate ligands. As a result, model mechanisms for cytochrome P-450 invoke a reactive intermediate that is formulated to be equivalent to Compound I of horseradish peroxidase, (por+-)Fe =0, with a high-potential porphyrin cation radical. Such a species would be reduced by thiolate, and therefore is an unreasonable formulation for the reactive center of cytochrome P-450. 

This is usually isolated from yeast, and has a molecular weight of 53 000 with one heme b. It catalyzes the oxidation of ferrocytochrome c by hydrogen peroxide. It is the first peroxidase for which the structure has been determined. The imidazole axial ligand is His-174, while Arg-48, Trp-51 and His-52 provide distal catalytic groups. The mechanism involves nucleophilic attack of peroxide on the Fe, loss of the ROOH proton to the imidazole of His-52, and transfer of this proton to the leaving RO group. Compound I of cytochrome c peroxidase is red, and differs from HRPI in that the additional oxidizing equivalent is on a protein residue. ESR and ENDOR spectra have been interpreted in terms of a methionine-centred free radical. One possibility is that a ferryl porphyrin cation radical is formed with cytochrome c peroxidase (it is attractive to assume that this would be common to all peroxidases), but that cytochrome c peroxidase has a readily oxidizable substrate which reduces the porphyrin radical. ... 

P-450 have also been discussed, especially homolysis and heterolysis of the acylperoxo-iron(lll) complex. In both cases, we consider the active species to be oxoferryl porphyrin cation radicals however, many different reactivities exist between peroxidases and P-450. Ortiz de Montellano et al. have proposed that the position of substrates in the active site might depend on the spatial characteristics of the individual enzymes and influence the detailed course of the reaction (139). These propositions should be carefully examined. Scheme XXV illustrates all of the intermediates that have been observed and/or proposed in the oxygen activation mechanism by P-450 and that have been prepared by the model systems. 

The proposed mechanism for these catalytic oxidations includes two catalytic redox cycles (i) initial oxidation of iodobenzene with Oxone, producing hydroxy(phenyl)iodonium ion and hydrated iodosylbenzene and (ii) the oxidation of iron(III)-porphyrin to the oxoiron(IV)-porphyrin cation-radical complex by the intermediate iodine(III) species (Scheme 4.58) [93]. The oxoiron(IV)-porphyrin cation-radical complex acts as the actual oxygenating agent toward aromatic hydrocarbons. The presence of the [PhI(OH)]+ and PhI(OH)2 species in solutions containing Phi and Oxone has been confirmed by ESI mass spectrometry [93]. 

The different mechanistic proposals for epoxidation reflect a complex oxidation pattern dependent on a variety of factors. At this time it does not seem either possible or necessary to accommodate all the observed features of metalloporphyrin catalyzed epoxidation within a single mechanism. The crucial importance of oxoiron(IV) porphyrin cation radicals has been established beyond doubt but the net 0-atom transfer to the olefin may perhaps occur via more than one kind of intermediate. 

The functionalization of zinc porphyrin complexes has been studied with respect to the variation in properties. The structure and photophysics of octafluorotetraphenylporphyrin zinc complexes were studied.762 Octabromoporphyrin zinc complexes have been synthesized and the effects on the 11 NMR and redox potential of 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetraarylporphyrin were observed.763 The chiral nonplanar porphyrin zinc 3,7,8,12,13,17,18-heptabromo-2-(2-methoxyphenyl)-5,10,15,20-tetraphenylporphyrin was synthesized and characterized.764 X-ray structures for cation radical zinc 5,10,15,20-tetra(2,6-dichlorophenyl)porphyrin and the iodinated product that results from reaction with iodine and silver(I) have been reported.765 Molecular mechanics calculations, X-ray structures, and resonance Raman spectroscopy compared the distortion due to zinc and other metal incorporation into meso dialkyl-substituted porphyrins. Zinc disfavors ruffling over doming with the total amount of nonplanar distortion reduced relative to smaller metals.766 Resonance Raman spectroscopy has also been used to study the lowest-energy triplet state of zinc tetraphenylporphyrin.767... 

The structure of HRP-I has been identified as an Fe(IV) porphyrin -ir-cation radical by a variety of spectroscopic methods (71-74). The oxidized forms of HRP present differences in their visible absorption spectra (75-77). These distinct spectral characteristics of HRP have made this a very useful redox protein for studying one-electron transfers in alkaloid reactions. An example is illustrated in Fig. 2 where the one-electron oxidation of vindoline is followed by observing the oxidation of native HRP (curve A) with equimolar H202 to HRP-compound I (curve B). Addition of vindoline to the reaction mixture yields the absorption spectrum of HRP-compound II (curve C) (78). This methodology can yield useful information on the stoichiometry and kinetics of electron transfer from an alkaloid substrate to HRP. Several excellent reviews on the properties, mechanism, and oxidation states of peroxidases have been published (79-81). 

This behavior, as well as complementary observations, can be explained on the basis of the reaction mechanism depicted in Scheme 5.3. The main catalytic cycle involves three successive forms of the enzyme in which the iron porphyrin prosthetic group undergoes changes in the iron oxidation state and the coordination sphere. E is a simple iron(III) complex. Upon reaction with hydrogen peroxide, it is converted into a cation radical oxo complex in which iron has a formal oxidation number of 5. This is then reduced by the reduced form of the cosubstrate, here an osmium(II) complex, to give an oxo complex in which iron has a formal oxidation number of 4. 

The first detailed research on the mechanism of electron phototransfer with the participation of MP in vitreous matrices appears to be ref. 55, which deals with the processes of charge separation in vitreous solutions of zinc and magnesium porphyrins in ethanol containing some addition of CC14 at 77 K. Illumination of the solutions in the Soret band or in long-wave bands of MP absorption results in a one-quantum ionization of MP and formation of MPf cation radicals and CC14 anion radicals recorded according to their characteristic EPR and optical spectra [56,57]... 

Co(0-NH2)TPP] was polymerized onto glassy-carbon electrodes from an electrolytic solution containing the monomer and tetraethylammonium perchlorate as the electrolyte by cycling the electrode potential in the oxidative way (26). The polymerization of this monomer appears to proceed through a radical cation of the porphyrin with a mechanism similar to that of the oxidative electropolymerization of aniline (27). 

Metalloporphyrins catalyze the autoxidation of olefins, and with cyclohexene at least, the reaction to ketone, alcohol, and epoxide products goes via a hydroperoxide intermediate (129,130). Porphyrins of Fe(II) and Co(II), the known 02 carriers, can be used, but those of Co(III) seem most effective and no induction periods are observed then (130). ESR data suggest an intermediate cation radical of cyclohexene formed via interaction of the olefin with the Co(III) porphyrin this then implies possible catalysis via olefin activation rather than 02 activation. A Mn(II) porphyrin has been shown to complex with tetracyanoethylene with charge transfer to the substrate (131), and we have shown that a Ru(II) porphyrin complexes with ethylene (8). Metalloporphyrins remain as attractive catalysts via such substrate activation, and epoxidation of squalene with no concomitant allylic oxidation has been noted and is thought to proceed via such a mechanism (130). Phthalocyanine complexes also have been used to catalyze autoxidation reactions (69). 

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