β-甲基亚硝基哌嗪致癌剂第二亲电中心邻基参与作用的理论研究

用从头计算Hartree-Fork方法和密度泛函B3LYP方法在6-311G(d)水平上对β-甲基亚硝基哌嗪类化合物代谢活化后的邻基参与作用机理进行了研究. 计算结果表明, 哌嗪环上N'原子和N'-取代基上氧原子的邻基参与作用明显提高了β-甲基亚硝基哌嗪代谢物的亲电反应活性, 促进了对DNA的烷化作用. 解释了甲基取代的N-亚硝基哌嗪较其母体化合物的致癌性具有显著增强的现象, 为N-亚硝基哌嗪在其γ-位形成第二亲电活性中心的致癌代谢途径提供了理论依据.

Theoretical Study on Anchimeric Assistance on the Second Electrophilic Region of Carcinogenic β-Methylnitrosopiperazine

The anchimeric assistant mechanism of the second electrophilic region on β-methylnitrosopiperazine was studied by using ab initio and density functional theory(DFT) method with the 6-311G(d) basis set. The results show that the anchimeric assistance of N' atom on the piperazine ring or the oxygen atom on the N'-substituted group enhances the reactivity of β-methylnitrosopiperazine metabolites, which can be used to explain the phenomenon that the carcinogenicity of methyl substituted N-nitrosopiperazines is much more potent than that of their parent compounds. This research provids a theoretical evidence for the formation of the second electrophilic region on the γ-positions of N-nitrosopiperazines in their carcinogenic metabolism.