期刊
DALTON TRANSACTIONS
卷 43, 期 39, 页码 14833-14840出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4dt02065k
关键词
-
资金
- Natural Science Foundation of China [21273095]
The anaerobic metabolism of CCl4 by P450 enzymes was investigated using quantum chemical calculations. It was found that under anaerobic conditions, the substrate CCl4 might undergo one or two subsequent one-electron reductions to generate different reactive metabolites, trichloromethyl radical ((CCl3)-C-center dot) and dichlorocarbene (:CCl2) respectively. Meanwhile, it was the reduced ferrous haem complex rather than the unreduced ferric haem complex that could directly achieve such reductions. Based on the formation of the former reactive metabolite, a further one-electron reduction could take place with the assistance of a proton to yield the latter reactive species, i.e., a further reductive dechloridation of (CCl3)-C-center dot could take place via a novel S(E)3 mechanism. In addition, the (CCl3)-C-center dot species was capable of binding covalently to the meso-carbon atom of the prosthetic group, leading to the suicidal destruction of P450 enzymes. Whereas the :CCl2 species was involved in the CCl4-dependent reversible P450 inhibition as its hydrolysis product, CO, but was not significantly involved in the CCl4-dependent irreversible P450 destruction. It is obvious that the reductive metabolism of CCl4 to reactive intermediates by P450 enzymes is an essential prerequisite for its toxicity.
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