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用从头计算法在MP2/6-311+G(d,p)水平上对3,5-二甲基-亚硝基哌嗪(DMNP)及其类似物经代谢生成DNA烷化剂的机理进行了研究.探讨了N’原子上取代基的变化对DMNP代谢物生成α-位和γ-位两个烷化中心的影响,解释了两个烷化中心的生成活性与化合物的致癌性之间的关系.结果表明,α-位和γ-位代谢物越容易生成活泼亲电中间体,其母体化合物的致癌活性越高.但如果有一个烷化中心丧失活性,就会明显减弱化合物的致癌活性.因此,DMNP类化合物的致癌性取决于其α-位和γ-位的协同烷化作用,在评价DMNP的致癌强度时需同时考虑两个烷化中心的烷化能力以及二者之间的关系.
The mechanism by which metabolism of 3,5-dimethyl-nitrosopiperazine (DMNP) and its analogs to DNA alkylating agents at the level of MP2 / 6-311 + G (d, p) The effects of the substitution of the substituents on the N ’atom on the two alkylating centers at α-position and γ-position of DMNP metabolites were discussed, and the relationship between the formation activity of two alkylating centers and the carcinogenicity of compounds was explained The results showed that the more active metabolites of α-position and γ-position produce active electrophilic intermediates, the higher the carcinogenic activity of the parent compound is, but if one alkylation center loses its activity, it will significantly reduce the carcinogenicity of the compound Therefore, the carcinogenicity of DMNP compounds depends on the synergistic alkylation at the α-position and the γ-site, and in assessing the carcinogenic strength of DMNP, both the alkylation capacity of the two alkylation centers and the Relationship.