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.