ABEEM/MM-MD模拟溶剂对N7质子化嘌呤核酸和芳香胺离子反应的影响

ABEEM/MM-MD simulation studies of the effects of solvent on the reactions concerning N7-protonated purine bases with arylnitrenium ions

芳香胺离子是芳香胺致癌进程中产生的中间体,它与嘌呤核酸反应,生成芳香胺-DNA加成物,从而导致癌症的发生。在之前的理论研究中,我们发现,N7质子化的嘌呤与芳香胺离子反应时,过渡态的气相和液相中激发能差别很大,其具体原因还不清楚。因此,本文中,应用ABEEM/MM-MD分子动力学模拟方法,研究了溶剂对这类反应的影响。在具体的溶剂模拟中,我们使用显含的水分子作为溶剂,模拟得到了整个反应过程中N7质子化嘌呤与芳香胺离子的水的径向分布函数。分析这些结果可以发现,当反应进行到有过渡态出现时,水溶剂与过渡态的相互作用会变的比反应初始阶段强得多。从这个结果,可以得到过渡态的激发能在气相和液相中差别很大的原因是,在液相反应中,水溶剂与过渡态比较强的相互作用降低了过渡态的激发能。此外,我们也使用ABEEM方法得到了所研究反应过程中的电荷变化情况。

Arylnitrenium ions are intermediate involved in the carcinogenic process of aromatic amines.They can react with purine nucleosides and form arylamine-DNA adducts,which cause severe mutations that ultimately lead to cancer.In a previous theoretical study, we found that the gas and aqueous activation energies of transition state in the reaction of N7-protonated purine bases with arylnitrenium ion had a dramatic difference.But the specific reason to the difference remains unclear.Thus,in this paper,we explored the effect of solvent on the reaction of N7-protonated purine bases with arylnitrenium ion using ABEEM/MM-MD simulation method.In our simulation,we use water molecular as explicit solvent and obtain radical distribution function of water in the whole reaction.On the basis of these results,we found that the interactions between water and transition state become stronger than those in the initial aqueous reaction.So we obtained the specific reason to the dramatic difference of activation energies of transition state in gas and aqueous reactions, that is the stronger interactions between water and transition state lower the activation energy of transition state in aqueous reaction. In addition,we also analyzed the charge distribution in researched reaction employing ABEEM method.