High-valent iron-oxo porphyrin

In the catalytic cycle in Scheme 1, details of the reaction between the high-valent iron-oxo porphyrin n radical cation [(P)Fe =0] + and a substrate have yet to be clarified [66]. Three possibilities have survived after extensive studies of the mechanisms of the reactions of high-valent iron-oxo porphyrins, in particular the dealkylation of amines by cytochrome P-450 (A) a sequential electron-proton electron transfer (B) direct hydrogen transfer then electron transfer and (C) electron transfer followed by hydrogen transfer (Scheme 2) [67-74]. 

Fig. 4.78. Role of the distal histidine in the "pull" mechanism for the cleavage of the dioxygen bond and creation of the high-valent iron-oxo porphyrin it cation radical (Compound I) in peroxidases.

Calculated spin distributions in high-valent iron-oxo porphyrin species. 

Fig. 4.88. Proposed radical-type reaction mechanisms for (a) aliphatic hydroxylation and (b) epoxidation by the high-valent iron-oxo porphyrin intermediate of cytochromes P450. The mechanism depicted in (a) is called the "oxygen-reboimd" mechanism.

Yamamoto, S J. Teraoka, and H. Kashiwagi (1988). Ab initio RHF and CASSCF studies on Fe-0 bond in high-valent iron-oxo porphyrins. J. Chem. Phys. 88, 303-312. 

The peroxidase activity of PGHS is comparable to that of better known peroxidases such as horseradish peroxidase (HRP). The catalytic cycle of HRP is shown in Figure 5 [9], Its first step is the formation of an intermediate very often found in hemoproteins by transfer of an oxygen atom from various oxygen atom donors to the Fe(III) heme (Eq. 6). It is a high-valent iron-oxo species, at least formally a Fe(V)=0 complex. In fact, the detailed electronic structure of this intermediate depends on the environment of the heme provided by the protein. In HRP, this intermediate (called compound I) is a (porphyrin radical-cation)-Fe(IV)=0 complex, as shown by many spectroscopic techniques [9],... 

All the proteins described in this chapter and that catalyze very different reactions involving 02 exhibit the following common characteristics (1) the presence of an iron porphyrin cofactor, (2) an axial iron ligand coming from the protein that is in most cases a histidine imidazole (except for cytochrome P-450), and (3) the intermediate formation of high-valent iron-oxo species, formally equivalent to Fe(IV)=0 or Fe(V)=0, which are key intermediates in the enzymatic reactions. The different reactions performed by these iron-oxo species and the different uses of 02 by the hemoproteins are due to the very different environments of the heme in these hemoproteins and to a more or less rapid electron transfer. As a function of its environment, the iron-oxo species may either be reduced into H20 if electrons are easily transferred to the heme or oxidize a substrate or a protein amino acid that could be present in close proximity in the active site (Figure 14). 

As for other peroxidases, a high-valent iron-oxo entity associated with a porphyrin 7r-radical-cation, Cpd I, is generated by the addition of hydrogen peroxide (see Scheme 3 for the catalytic cycle of LiP). This green compound (Soret band at 408 nm) has UV-visible and EPR characteristics similar to that of HRP-Cpd 1. ... 

A synthetic iron porphyrin with a thiolato ligand in the axial position has been oxidized by hydrogen peroxide in the presence of chloride. The shift of the Soret band from 408 nm to 404 nm might be due to the formation of a putative Fe OCl entity which can generate free HOCl after protonation. " The kinetic parameters of halide oxidation by a high-valent manganese-oxo porphyrin complex have been reported. ... 

It has been widely accepted that the high-valent iron oxo complex 1 is the active oxidant in metalloporphyrin systems and in non-porphyrin iron complex systems as well. A high-valent iron oxo species can be formed via heterolytic 0-0 bond cleavage of the iron-hydroperoxide 2 or of the iron-peroxyacid species 4 (Figure 5, pathway A). Recently, elegant proof of this heterolytic 0-0 bond cleavage of hydrogen peroxide, MCPBA, and f-butyl hydroperoxide has been provided by Traylor et al in iron porphyrin... 

The most notable reaction is that of metal-oxygen species with substrate. In the case of heme iron monooxygenases, high-valent iron-oxo species such as 3 or 4 in Fig. 5 are believed to react with substrates. On the other hand, both hydroperoxo (2) and 0x0 (3) are proposed for reactions by nonheme iron oxygenases. There are discussions on whether the iron-oxo species (3) is stabilized in the nonheme oxygenases in the absence of a porphyrin ligand which is effective to form 4. However, the iron-oxo species is attractive for explanation of the results obtained by monooxygenations by nonheme model iron systems. 

Nam, W., Goh, Y. M., Lee, Yoon J., Lim, M. H., and Kim,. (1999) Biomimetic alkane hydroxylations by an iron(III) porphyrin complex with H2O2 and by a high-valent iron(IV) oxo porphyrin cation radical complex, Inorg. Chem. 38, 3238-3240. 

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