Nucleophilicity of Iron-Peroxo Porphyrin Complexes

Abstract

For the past 20 years, cytochrome P450 researchers have sought to identify and to characterize the reactive intermediates in reactions of these enzymes. This review focuses on one of those postulated intermediates, the ferric heme peroxo complex, [(porphyrin)Fe(III)(O₂ ^2-)]^-, a species which has been postulated to be formed transiently in the P450 catalytic cycle. Ferric peroxo porphyrin complexes, inorganic complexes that model the peroxo species, have been synthesized and their chemical reactivities characterized for comparison with the enzymes. Such studies have identified certain peroxo porphyrins as remarkably strong nucleophiles capable of oxidizing a variety of electron-poor molecules. While the ferric heme peroxo intermediate, in the majority of P450 enzymes, rapidly converts to an oxoferryl species, some enzymes, e.g., aromatase, lanosterol 14α-demethylase, progesterone 17α-hydroxylase/17,20-lyase, and NO synthase, appear to use this intermediate as the active oxidant. Additionally, studies of ferric peroxo porphyrin complexes have increased our understanding of the nature of the P450 catalytic cycle and of the mechanisms of generation of other reactive intermediates used in P450 enzymes.