丙二醛与DNA碱基交联反应的AM1研究

采用量子化学ＡＭ１方法对丙二醛与ＤＮＡ碱基对的加合反应进行了计算，从电荷分布、几何构型及能量变化等方面分析了反应的动力学及热力学特征．结果显示：丙二醛与Ｇ－Ｃ或Ａ－Ｔ碱基对经亲核加成反应而发生交联，反应分３步完成，生成过渡态１为反应的动力学决定步骤，有较高的活化能．总反应为放热过程，在热力学上十分有利于反应的发生．加成过程中电子由碱基向丙二醛转移，羰基氧的质子化对电子转移起促进作用．丙二醛与ＤＮＡ互补碱基对形成加成产物后可引起ＤＮＡ在复制中的编码错误，从而导致其致癌性．

AM1 Study on the Cross Linking Reactions Between DMA and DNA Bases

AM1 calculations were performed on the adduction reactions between malondialdehyde (MDA) and DNA bases. The dynamic and thermal characteristics of the reactions were analyzed from the viewpoint of geometry ical structure, electric charges distribution, and energy change. It was concluded that additive reactions, initiated by the nucleophilic atoms in DNA bases attacking the carbonyl in MDA, take place in three steps with the results of DNA cross-link. The formation of TS1, with large activation energy, is the determinant step. The total reactions are exothermal, therefore are easy to occur thermo-dynamically. Electrons transfer from bases to MDA during the reaction progress, while the protonation of carbonyl oxygen facilitates this process. The formation of crosslinking between MDA and DNA bases can cause the coding errors during DNA replica. That may be the essential origin of the carcinogenesis of MDA.