title: P(450)/NADPH/O(2)- and P(450)/PhIO-catalyzed N-dealkylations are mechanistically distinct.
abstract: A high-valent iron-oxo species analogous to the compound I of peroxidases has been thought to be the activated oxygen species in P450-catalyzed reactions. Spectroscopic characterization of the catalytically competent iron-oxo species in iodosobenzene (PhIO)-supported model reactions and parallels between these model reactions and PhIO- and NADPH/O2-supported P450 reactions have been taken as strong evidence for this proposal. To support this proposal, subtle differences observed in regio- and chemoselectivities, isotope effects, and source of oxygen, etc., between NADPH/O2- and PhIO-supported P450 reactions have been generally attributed to reasons other than the mechanistic differences between the two systems. In the present study, we have used a series of sensitive mechanistic probes, 4-chloro-N-cyclopropyl-N-alkylanilines, to compare and contrast the chemistries of the NADPH/O2- and PhIO-supported purified CYP2B1 N-dealkylation reactions. Herein we present the first experimental evidence to demonstrate that the NADPH/O2- and PhIO-supported P450 N-dealkylations are mechanistically distinct and, thus, the P450/PhIO system may not be a good mechanistic model for P450/NADPH/O2-catalyzed N-dealkylations.
authors.affiliation: Department of Chemistry, Wichita State University, Wichita, KS 67260-0051, USA.
authors.forename: Mehul N
authors.initials: MN
authors.lastname: Bhakta
authors.forename: Paul F
authors.initials: PF
authors.lastname: Hollenberg
authors.forename: Kandatege
authors.initials: K
authors.lastname: Wimalasena
mesh_terms: D000478:Alkylation; D002384:Catalysis; D019362:Cytochrome P-450 CYP2B1 / Q000737:chemistry* / Q000378:metabolism; D007462:Iodobenzenes / Q000737:chemistry* / Q000378:metabolism; D009249:NADP / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism
chemical_list: D007462:Iodobenzenes; D009249:NADP; D019362:Cytochrome P-450 CYP2B1; D010100:Oxygen; C037276:iodosobenzene