Reactions of guanine with methyl chloride and methyl bromide: O6‐methylation versus charge transfer complex formation
Reactions of guanine with methyl chloride and methyl bromide: O6‐methylation versus charge transfer complex formation
复制标题
DOI：
10.1002/qua.21233
复制
发表时间：
2007
影响因子：
2.2
通讯作者：
P. Shukla;P. Mishra;S. Suhai
中科院分区：
文献类型：
--
作者：
P. Shukla;P. Mishra;S. Suhai
采用密度泛函理论（DFT）方法，在B3 LYP/6-31+G* 和B3 LYP/AUG-cc-pVDZ水平上研究了鸟嘌呤与氯甲烷和溴甲烷反应产生的O 6-甲基化反应，解释了卤甲烷具有遗传毒性和致突变、致癌特性的原因.在气相中，反应物复合物（RC）和产物复合物（PC）中涉及的各种孤立物种的几何形状进行了优化。在相同的理论水平下，气相中连接反应物络合物与产物络合物的过渡态也进行了优化。利用自洽反应场理论的极化连续模型（PCM），对反应物配合物、产物配合物和过渡态在水溶液中进行了溶剂化。在每种情况下，对总能量进行零点能（ZPE）校正，并对焓进行相应的热能校正。鸟嘌呤的酮式与氯甲烷和溴甲烷在水中的反应物复合物比涉及鸟嘌呤的烯醇式的相应复合物明显更稳定。产物络合物中的结合性质被发现是电荷转移类型（O 6 mG+ · X−，XCl，Br）。HCl，HBr，和H2O分子与鸟嘌呤的酮形式得到的PC的结合并没有改变在PC中的卤素阴离子的位置，和PC的电荷转移字符也没有修改，由于这种结合。此外，由于HCl，HBr和H2O分子与PC的结合而获得的复合物比分离的PC具有更大的稳定性。发现参与PC形成的反应势垒相当高（约50 kcal/mol）。卤代甲烷引起的遗传毒性、致突变和致癌机制似乎涉及电荷转移型复合物的形成。因此，这些涉及卤代甲烷的过程的机制似乎与涉及其他强致癌甲基化剂的机制完全不同。© 2006 Wiley Periodicals，Inc.国际量子化学杂志，2007年
Density functional theory (DFT) at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels was employed to study O6-methylation of guanine due to its reactions with methyl chloride and methyl bromide and to obtain explanation as to why the methyl halides cause genotoxicity and possess mutagenic and carcinogenic properties. Geometries of the various isolated species involved in the reactions, reactant complexes (RCs), and product complexes (PCs) were optimized in gas phase. Transition states connecting the reactant complexes with the product complexes were also optimized in gas phase at the same levels of theory. The reactant complexes, product complexes, and transition states were solvated in aqueous media using the polarizable continuum model (PCM) of the self-consistent reaction field theory. Zero-point energy (ZPE) correction to total energy and the corresponding thermal energy correction to enthalpy were made in each case. The reactant complexes of the keto form of guanine with methyl chloride and methyl bromide in water are appreciably more stable than the corresponding complexes involving the enol form of guanine. The nature of binding in the product complexes was found to be of the charge transfer type (O6mG+ · X−, XCl, Br). Binding of HCl, HBr, and H2O molecules to the PCs obtained with the keto form of guanine did not alter the positions of the halide anions in the PCs, and the charge transfer character of the PCs was also not modified due to this binding. Further, the complexes obtained due to the binding of HCl, HBr, and H2O molecules to the PCs had greater stability than the isolated PCs. The reaction barriers involved in the formation of PCs were found to be quite high (∼50 kcal/mol). Mechanisms of genotoxicity, mutagenesis and carcinogenesis caused by the methyl halides appear to involve charge transfer-type complex formation. Thus the mechanisms of these processes involving the methyl halides appear to be quite different from those that involve the other strongly carcinogenic methylating agents. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007