烷基亚硝胺非α-位代谢产物反应活性从头算研究

Ab initio Study on the Reactivity ofNon-α-metabolites of Alkylnitrosamines

甲基正烷基亚硝胺通过非α-位代谢产生的亲电活性中心在化学致癌过程中具有重要作用.采用从头计算方法比较了甲基乙基亚硝胺和甲基丙基亚硝胺β-位或γ-位代谢形成的硫酸酯、磷酸酯和葡萄糖醛酸酯在亚硝基的邻基参与作用下的反应活化能以及过渡态和中间体的分子结构.计算结果表明,硫酸酯的反应活性明显高于磷酸酯和葡萄糖醛酸酯,而β-位代谢物受邻基参与的促进作用更大.

The non-α-position metabolites of nitrosamines play an important role in chemical carcinogenesis. Ab initio computations are carried out to study the reactivity of β-and γ-position metabolites of methylakylnitrosamines. Taking N-methyl-N-nitroso-2-（sulfate）ethylamine（ Ⅰ ）, N-methyl-N-nitroso-2-（phosphate）ethylamine（ Ⅱ ）, N-methyl-N-nitroso-2-（glucuronate）ethylamine（ Ⅲ ）, N-methyl-N-nitroso-3-（sulfate）-propylamine （ Ⅳ）, N-methyl-N-nitroso- 3-（phosphate）propylamine（ Ⅴ）, and N-methyl-N-nitroso-3-（glucuronate）propylamine （Ⅵ） as models, we investigate their reactivity with the anchimeric assistant process of the N-nitroso groups. Full geometric structure optimization has been done for all reactants, intermediates and transition states. The activation energies, vibrational frequencies and IRC are also obtained. All computations are performed at RHF/6-31G（d） and MP2/6-31G（d） levels. The results show that the reactivity of the sulfates （ Ⅰ and Ⅳ） are obviously higher than those of the phosphates （ Ⅱand Ⅴ） and the glucuronates （Ⅲ and Ⅵ）. And these data indicate that the anchimeric assistance is much more efficient when the leaving group is on the β-carbon than on the γ-carbon.