Heme catalytic oxidation

Kinetic studies have shown that the product formed in the reaction of the fully oxidized enzyme with hydrogen peroxide is catalytically inactive. Reaction of the half-reduced enzyme with hydrogen peroxide leads to an enzymatically active compound, in which the Fe" heme is oxidized to Fe, and the FeIU heme is oxidized to the FeIV ferryl species. No stoichiometric formation of a radical species is observed, unlike the case for other peroxidases. The peroxide-oxidized enzyme will then oxidize two molecules of reduced cytochrome c. Mechanistic details are still unclear, particularly with regard to the interaction between the two heme groups, a phenomenon revealed by ESR studies.1373... 

Fig. 5.11 Modification of the vinyl groups of the prosthetic heme of HRP upon catalytic oxidation of nitrite to N02 or Br to HOBr. For each reaction, two different modifications of the vinyl groups are shown. These modifications can occur in different combinations. For example in the Br reaction, both of the vinyls could he present as bromohydrin [-CHBrCH2OH] adducts...

The problems connected with the high cost and low stability of peroxidases, which limits their potential applications in processes of industrial interest, can be possibly overcome, at least in part, by the use of heme-peptide complexes as small-size peroxidase analogs. In this context, we will consider only the heme-peptide complexes more strictly related to the peroxidases, and will not deal with the extensive literature about catalytic oxidations by synthetic metalloporphyrins. It is difficult to reproduce in a synthetic molecule the peculiar features of complex enzymes such as... 

The N-alkylation reaction represents a bifurcation of the normal alkene epoxidation reaction cycle and, therefore, N-alkylation is a suicide event that leads to catalytic inhibition in the native system. With synthetic tetraarylporphyrins that mimic the N-alkylation reaction, the use of halogen-substituted catalysts that are stable toward oxidative degradation (26, 27) provide the most useful model systems because the heme model remains intact for a significantly greater number of turnovers than the partition number. The partition number is the ratio of epoxidation cycles to N-alkylation cycles, i.e., N-alkyl porphyrins are formed before the heme is oxidatively destroyed. 

P450-catalyzed oxidation of terminal acetylenes to substituted acetic acids (Chapter 6) is more prone to result in heme alkylation than the oxidation of terminal olefins. The structure-activity relationships for the acetylene reaction are similar to those for terminal olefins, except that there are fewer instances in which the reaction does not result in errzyme inactivation. For example, P450 is inactivated by phenylacetylene but not delectably by styrene ", and P450 is inactivated by internal acetylenes, albeit without heme adduct formation, but not by internal olefins 22 , Catalytic oxidation of the acetylenic function is required for enzyme inactivation and terminal acetylenes give heme adducts analogous to those obtained with terminal olefins - 259 jhe salient difference in the adducts obtained with acetylenes and olefins... 

During the catalytic oxidation of some substrates, certain P450 enzymes (i.e. CYP3A, CYP2E) undergo a mechanism-based inactivation process in which fragments of the heme are irreversibly bound to the protein. Examples of such inactivators include spironolac-... 

Ortiz de Montellano, P.R. and L.A. Grab (1986). Inactivation of cytochrome P-450 during catalytic oxidation of a 3-[(arylthio)ethyl]sydnone N-vinyl heme formation via insertion into the Fe-N bond. J.Am. Chem. Soc. 108, 5584-5589. 

Kinetic studies have shown that the product formed in the reaction of the fully oxidized enzyme with hydrogen peroxide is catalytically inactive. Reaction of the half-reduced enzyme with hydrogen peroxide leads to an enzymatically active compound, in which the Fe heme is oxidized... 

The present review has outlined the efforts to develop biomimetic non-heme iron and manganese catalysts for alkane hydroxylation, olefin epoxidation, and cis-dihydroxylation reactions. However, the examples reviewed here are mostly presented as reported in the literature, since the various reaction conditions involved in the catalytic oxidations hamper a direct comparison and critical evaluation of the data. The survey has not only illustrated a rich variety of iron and manganese complexes that lead to the successful structural modeling of important non-heme iron and manganese enzymes, but also significant features of the oxidation reactions catalyzed by these complexes in combination with dihydrogen peroxide. 

Girerd, J. J. Banse, F. Simaan, A. J. Characterization and properties of non-heme iron peroxo complexes. In Metal-Oxo and Metal-Peroxo Species in Catalytic Oxidations Structure Bonding wo. 97, Springer-Verlag, 2000, p. 145. 

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