Nucleophilicity of iron-peroxo porphyrin complexes

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