Role of perferryl-oxo oxidant in alkane hydroxylation catalyzed by cytochrome P450: a hybrid density functional study.

We have performed hybrid density functional theory (DFT) calculations on the reactivities of low-lying doublet and quartet ferryl-oxo [Fe(IV)═O] oxidants and a doublet perferryl-oxo [Fe(V)═O] oxidant as a new key active species in cytochrome P450. Several aspects of the mechanism of hydrogen-atom abstraction from propane by the above active species of compound I models have been addressed in detail. The results, based on fully optimized structures, demonstrate that the perferryl-oxo oxidant can contribute to the reactivity of compound I owing to the presence of a highly reactive pπ atomic radical character of the oxo ligand. The perferryl-oxo species can abstract a hydrogen atom from propane with an activation barrier of only 0.6-2.5 kcal mol(-1), which is substantially smaller than that for the ferryl-oxo species (13.4-17.8 kcal mol(-1)). The role of the doublet perferryl species in the heterolytic and homolytic O-O bond cleavage in precursor (protonated) compound 0 coupled with the subsequent C-H bond activation has also been explored by grid search of ferryl and perferryl potential surfaces using two parameters. Our calculations suggest that the perferryl-oxo oxidant is catalytically competent, if the O-O bond cleaves heterolytically. The interplay between the accessible ferryl and perferryl states of compound I with quite different reactivities could be a possible reason for elusiveness of compound I in native P450 catalysis on the one hand and various degrees of detection in shunt reactions using peroxy acids on the other hand.