二正烷基亚硝胺第二活性区对致癌作用机理的理论研究

THE THEORETIC STUDIES OF THE SECOND ACTIVE REGION OF DIALKYLNITROSAMINE ON CARCINOGENESIS MECHANISM

采用MNDO方法计算了对称二烷基亚硝胺β-,γ-和δ-位硫酸酯经SN2反应机制与DNA碱基腺嘌呤(A)发生烷化反应的速率控制步骤的势能曲线和活化能,以及β-位硫酸酯经邻基参与作用与腺嘌呤烷化反应过程的势能变化.结果表明,邻基参与作用有利地促进了烷基亚硝胺与DNA的烷化反应,提高了β-位硫酸酯烷化DNA的能力,以此可以解释β-位硫酸酯化的二烷基-N-亚硝基化合物的致癌活性大于γ-和δ-位硫酸酯化的二烷基-N-亚硝基化合物的致癌活性.使得β-位有可能成为亚硝胺的第二亲电活性区.

The reactions of several α,β-, or 5-sulphate dialkylnitrosamines with adenine (A) of DNA have been studied with MNDO semiempirical method. The computed active energies of sulphate di-ethyl- , dipropyl- and dibutyl- nitrosamines through SN2 mechanism are nearly equal, but higher than that of β-sulphate-diethylnitrosarnine reacting with A through forming five-member ring intermediate by anchimeric assistant mechanism. It means that anchimeric assistant effect increases the alkylation ability of β-sulphate-dialkylnitrosamines, so can explains the fact that β-sulphate-di-alkylnitrosamines have more carciogenic potency than other position sulphate-dialkylnitrosarnines. This result suggests that the β-position may be the second electrophilic region produced through metabolism, there by gives the theoretic support to the di-region theory.