title: One oxidant, many pathways: a theoretical perspective of monooxygenation mechanisms by cytochrome P450 enzymes.
abstract: Density functional theoretical studies of monooxygenation reactivity of the high-valent oxoiron(IV) porphyrin cation-radical compound of cytochrome P450, the so-called Compound I, and of its precursor, the ferric(III)-hydroperoxide species, are described. The degeneracy of the spin states of Compound I, its electron deficiency, and dense orbital manifold lead to two-state and multi-state reactivity scenarios and may thereby create reactivity patterns as though belonging to two or more different oxidants. Most of the controversies in the experimental data are reconciled using Compound I as the sole competent oxidant. Theory finds ferric(III)-hydroperoxide to be a very sluggish oxidant, noncompetitive with Compound I. If and when Compound I is absent, P450 oxidation will logically proceed by another form, but this has to be more reactive than ferric(III)-hydroperoxide. Theoretical studies are conducted to pinpoint such an oxidant for P450.
authors.affiliation: Department of Organic Chemistry and the Lise Meitner Minerva Center for Computational Quantum Chemistry, Hebrew University, 91904 Jerusalem, Israel. sason@yfaat.ch.huji.ac.il
authors.forename: Sason
authors.initials: S
authors.lastname: Shaik
authors.forename: Samuël P
authors.initials: SP
authors.lastname: de Visser
authors.forename: Devesh
authors.initials: D
authors.lastname: Kumar
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D006900:Hydroxylation; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D008665:Metalloporphyrins; D009942:Organometallic Compounds; D016877:Oxidants; D003577:Cytochrome P-450 Enzyme System