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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.
It is of great significance for the risk assessment of pollutants to develop a toxicological prediction method for the pathway and mechanism of toxic substances being catalyzed by cytochrome P450.According to the density functional theory calculations, it is revealed that the cytochrome P450 enzyme activity center (CpdI) Catalytic oxidation of 1,2-dibromo-3-chloropropane (DBCP) reaction mechanism and investigated the effect of kinetic isotope effect.The results show that there is a significant difference between the hydroxylation of DBCP and alkane hydroxylation reaction mechanism. DBCP hydroxylation reaction is spin-selective reaction.In addition, DBCP hydroxylation in the second step of the rebound process barrier was significantly higher than the alkylation of alkanes .Smiro-density analysis showed that the DBCP hydroxylation reaction Hydrogen extraction step is a hydrogen atom transfer process. Hydroxylation of DBCP has obvious kinetic isotope effect (KIE), and the temperature and tunneling effect have a significant effect on KIE value.This study can predict the bioconversion of halogenated alkanes Provide a theoretical basis.