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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。
Aromatic amine ions are intermediates produced by carcinogenicity of aromatic amines, which react with purine nucleic acids to form aromatic amine-DNA adducts, leading to the development of cancer. In the previous theoretical study, we found that the specific reasons for unclearing the excitation energies in the vapor phase and in the liquid phase of the transition state when N7 protonated purines react with aromatic amine ions. Therefore, in this paper, ABEEM / MM-MD molecular dynamics simulation method was used to study the effects of solvents on these reactions. In the specific solvent simulation, we use the water molecules as the solvent to simulate the radial distribution function of N7 protonated water and the aromatic amine ions during the whole reaction process. Analysis of these results shows that when the reaction proceeds to a transition state, the interaction of the water solvent with the transition state becomes much stronger than at the initial stage of the reaction. From this result, the reason why the excited state energy of the transition state is very different between the gas phase and the liquid phase can be obtained because the strong interaction between the water solvent and the transition state lowers the excitation energy of the transition state in the liquid phase reaction. In addition, we also used the ABEEM method to obtain the charge change during the reaction under study.