2＇-脱氧胞苷-5＇-磷酸羟基加合物的分子结构与电子结构

Molecular Geometries and Electronic Structures of Adducts between 2′-Deoxycytidine-5′-monophosphate Acid and Hydroxyl Radical

使用密度泛函理论(DFT)的B3LYP/DZP++研究了羟基自由基与2′-脱氧胞苷-5′-磷酸(dCMP)的胞嘧啶环加成产物的分子结构与电子结构.结果表明,dCMP胞嘧啶环中各C原子上的单羟基加合物的相对稳定性顺序为C5>C6垌C4≥C2.加合物的稳定性、自旋密度、静电势以及dCMP的电子密度、静电势、电荷分布分析表明,dCMP遭遇多个羟基自由基攻击时,第一个羟基自由基加在dCMP的C5上,而C6则成为第二个羟基自由基的进攻目标.反应中一旦形成了C2-位单羟基加合物,则极有可能在DNA复制过程中引起致命的基因突变,也可能诱发DNA-DNA以及DNA-蛋白质的链间交联,引起更复杂的损伤.相反,C5、C6-位上单羟基加合物的形成对DNA的稳定性不构成直接威胁.

Molecular geometries and electronic structures of adducts between the hydroxyl radical and the cytosine of 2＇-deoxycytidine-5＇-monophosphate acid （dCMP） were investigated by density functional theory, B3LYP/DZP＋＋. Computational results reveal that the relative stability sequence of single hydroxyl radical adducts of cytosine of dCMP is C5〉C6≥C4≥C2. The C5 atom of dCMP is most reactive for addition of the first hydroxyl radical whereas the C6 atom is not only the next most reactive site for addition of the first hydroxyl radical but also the second reactive site for the second hydroxyl radical addition when one dCMP molecule is attacked by multiple hydroxyl radicals. This sequence was established by analyses of their stabilities, spin densities, electrostatic potentials of adducts and electron densities, electrostatic potentials, and charge distributions of dCMP. Once the C2-adduct of dCMP is produced either a fatal gene mutation during DNA replication or a DNA-DNA, DNA-protein cross-link leading to more complicated damage of DNA might occur. In contrast, neither the C5- nor C6- adduct of dCMP has a significant effect on the stability of DNA.