title: Role of perferryl-oxo oxidant in alkane hydroxylation catalyzed by cytochrome P450: a hybrid density functional study.
abstract: 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University , Toyonaka, Osaka 560-0043, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.forename: Kizashi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Okumura
authors.forename: Jiro
authors.initials: J
authors.lastname: Shimada
mesh_terms: D000473:Alkanes / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011789:Quantum Theory
chemical_list: D000473:Alkanes; C066318:perferryl iron; D003577:Cytochrome P-450 Enzyme System; D007501:Iron