P450/NADPH/O2- and P450/PhIO-Catalyzed N-Dealkylations Are Mechanistically Distinct

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• 作者：Mehul N. Bhakta ; Paul F. Hollenberg ; and Kandatege Wimalasena
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：February 9, 2005
• 年：2005
• 卷：127
• 期：5
• 页码：1376 - 1377
• 全文大小：34K
• 年卷期：v.127,no.5(February 9, 2005)
• ISSN：1520-5126

文摘

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.