中文摘要：

发展有毒物质被细胞色素P450酶催化转化途径和机理的计算毒理预测方法,对于污染物的风险评价具有重要意义.本研究通过密度泛函理论计算,揭示了细胞色素P450酶活性中心（CpdI）催化氧化1,2-二溴-3-氯丙烷（DBCP）的反应机理,并考察了动力学同位素效应的影响.结果显示,DBCP羟基化反应与烷烃羟基化反应机理存在明显差异.不同于一般的双态反应,DBCP羟基化反应是自旋选择性反应.此外,DBCP羟基化第二步反弹过程中的能垒明显的高于烷烃羟基化过程.自旋密度分析表明,DBCP羟基化反应的氢提取步骤是一个氢原子转移过程.DBCP羟基化反应具有明显的动力学同位素效应（KIE）,且温度和隧道效应对KIE值具有明显的影响.本研究可为卤代烷烃类化合物的生物转化预测提供理论依据.

英文摘要：

The mechanism and kinetic isotope effect （KIE） on hydroxylation of 1,2-dibromo-3-chloropropane （DBCP） catalyzed by Coumpoud I, the active species of cytochrome P450 enzyme, were investigated by the density functional theory computation. The enzymatic and aqueous environment was simulated by the polarizable continuum model. The results show there are some obvious differences between the hydroxylation of DBCP and alkanes. Compared with the two-state-reaction of the hydroxylation of alkanes, the hydroxylation of DBCP is a spin selective reaction. Moreover, the barrier of the rebound process is obviously higher than the hydroxylation reaction of alkanes. The calculated spin densities reveal that the C-H bond activation steps are hydrogen atom transfer processes. The calculated KIE values are typical values of hydrogen atom abstraction process. The KIE values are also sensitive to the temperature and quantum tunneling effects in the hydroxylation of DBCP.