Microsomal P450-catalyzed N-dealkylation of N,N-dialkylanilines: evidence for a C(alpha)-H abstraction mechanism.
Microsomal P450-catalyzed N-dealkylation of N,N-dialkylanilines: evidence for a C(alpha)-H abstraction mechanism.
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DOI：
10.1021/ja011041d
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发表时间：
2002-02
影响因子：
15
通讯作者：
Mehul N Bhakta;K. Wimalasena
中科院分区：
文献类型：
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作者：
Mehul N Bhakta;K. Wimalasena
早期提出的p450催化的N，N-二烷基胺的N-脱烷基反应是通过单电子转移（SET）机制进行的，这一观点后来受到质疑，转而支持C(α)-H萃取机制。在本研究中，使用一系列n -烷基- n -环丙基-对氯苯胺探针，以苯巴比妥诱导的大鼠肝微粒体P450酶为模型系统，研究P450催化的n -脱烷基反应是否通过C(α)-H提取和/或SET机制进行。虽然这些发现与C(α)-H抽象机制高度一致，但可能需要进一步的实验证据来完全排除SET机制。
The early proposal that P450-catalyzed N-dealkylation of N,N-dialkylamines proceeds through a single-electron-transfer (SET) mechanism was later challenged in favor of the C(alpha)-H abstraction mechanism. In the present study, a series of N-alkyl-N-cyclopropyl-p-chloroaniline probes have been used to examine whether the P450-catalyzed N-dealkylations proceed through a C(alpha)-H abstraction and/or a SET mechanism, using phenobarbital-induced rat liver microsomal P450 enzymes as a model system. While the findings are highly consistent with a C(alpha)-H abstraction mechanism, further experimental evidence may be necessary to completely rule out the SET mechanism.