期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 510, 期 1, 页码 35-41出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2011.03.007
关键词
Kinetic isotope effect; Reaction mechanism; Cytochrome P450; Alkaloids; DFT
资金
- European Community [PIEF-GA-2008-219821]
- Nantes Metropole France
- ANR [ANR-08-PCVI-0017]
- Agence Nationale de la Recherche (ANR) [ANR-08-PCVI-0017] Funding Source: Agence Nationale de la Recherche (ANR)
(15)N heavy isotope effects are especially useful when detail is sought pertaining to the reaction mechanism for the cleavage of a C-N bond. Their potential in assisting to describe the mechanism of N-demethylation of tertiary amines by the action of cytochrome P450 monooxygenase has been investigated. As a working model for the first step, oxidation of the N-methyl group to N-methoxyl, tropine and a cytochrome P450 monooxygenase reaction centre composed of a truncated heme with sulfhydryl as the axial ligand were used. It is apparent that this first step of the reaction proceeds via a hydrogen atom transfer mechanism. Transition states for this step are described for both the high spin ((4)TS(H)) and low spin ((2)TS(H)) pathways in both gas and salvation states. Hence, overall normal secondary (15)N KIE could be calculated for the reaction path modeled in the low spin state, and inverse for the reaction modeled in the high spin state. This partial reaction has been identified as the probable rate limiting step. The model for the second step, fission of the C-N bond, consisted of N-methoxylnortropine and two molecules of water. A transition state described for this step, TS(CN), gives a strongly inverse overall theoretical (15)N KIE. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据