title: Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory.
abstract: Recent computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile the dilemma of the consensus 'rebound mechanism' of alkane hydroxylation, which emerged from experimental studies of ultra-fast radical clocks. The dilemma, stated succinctly as 'radicals are both present and absent and the rebound mechanism is both right and wrong', is simply understood once one is cognizant that the mechanism operates by two states, one low-spin (LS) the other high-spin (HS). In both states, bond activation proceeds in a manner akin to the rebound mechanism, but the LS mechanism is effectively concerted, whereas the HS is stepwise with incursion of radical intermediates.
authors.affiliation: Department of Organic Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, Hebrew University, 91904 Jerusalem, Israel.
authors.forename: Sason
authors.initials: S
authors.lastname: Shaik
authors.forename: Samuël P
authors.initials: SP
authors.lastname: de Visser
authors.forename: François
authors.initials: F
authors.lastname: Ogliaro
authors.forename: Helmut
authors.initials: H
authors.lastname: Schwarz
authors.forename: Detlef
authors.initials: D
authors.lastname: Schröder
mesh_terms: D000473:Alkanes / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry*; D005030:Ethylenes / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D006900:Hydroxylation; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011166:Porphyrins / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000473:Alkanes; D004852:Epoxy Compounds; D005030:Ethylenes; D005609:Free Radicals; D008024:Ligands; D011166:Porphyrins; D003577:Cytochrome P-450 Enzyme System; C036216:ethylene; D007501:Iron