Kinetic isotope effects implicate the iron-oxene as the sole oxidant in P450-catalyzed N-dealkylation

被引：52

作者：

Dowers, TS ^{[1
]}

Rock, DA ^{[1
]}

Jones, JP ^{[1
]}

机构：

[1] Washington State Univ, Dept Chem, Pullman, WA 99164 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2004年 / 126卷 / 29期

关键词：

D O I：

10.1021/ja0486364

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Multiple oxidants have been implicated as playing a role in cytochrome P450-mediated oxidations. Herein, we report results on N-dealkylation, one of the most facile reactions mediated by P450 enzymes. We have employed the N-oxides of a series of para-substituted 13C2H2-labeled N,N-dimethylanilines to function as both substrates and surrogate oxygen atom donors for P450cam and P4502E1. Kinetic isotope effect profiles obtained using the N-oxide system were found to closely match the profiles produced using the complete NAD(P)H/NAD(P)-P450 reductase/O2 system. The results are consistent with oxidation occurring solely through an iron-oxene species. Copyright © 2004 American Chemical Society.

引用

页码：8868 / 8869

页数：2

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