Fapy-G对碱基氢键复合物影响的理论研究

Theoretical Studies on the Effect of Fapy-G on Base Pair Hydrogen Bond Complexes

应用量子化学方法对2，6-二氨基4-羟基-5．甲酰胺嘧啶（Fapy-G）与正常碱基作用形成的20种氧化碱基对的多种性质进行了理论分析，碱基G的c8位被氧化后N7和N9位分别增加一个H原子，使其由氢键受体变成氢键供体，N7，N9及06原子所带的电荷变负，同时06作为氢键受体的能力增强．与碱基单体相比，碱基对中形成氢键的受体原子所带的电荷平均减小0．05e；供体H原子所带的电荷平均增大0．02e．Fapy—G分子中六元环上受体N原子参与形成氢键时，环的呼吸振动模式和N与对位C的振动模式的振动频率蓝移；与氢键相关的振动频率红移．所有氧化碱基对中，NH…N比NH…O氢键作用更强，且在NH…N氢键中，在六元环上的供体N原子形成的氢键比在氨基或开环上的供体N原子形成的氢键强．Fapy—G与碱基A作用结合能区域顺序为1〉2〉4〉3，与碱基T（R）作用区域顺序为3=4〉1〉2；水溶液使Fapy—G与碱基C作用的结合能减弱程度最大，结合能达到41．84—58．58kJ／mol，且使碱基对结合能力次序发生改变．

One of the primary oxidative DNA damage is 2,6-diamino-4-hydroxy-5-formamido pyrimidine, named Fapy-guanine（ Fapy-G）, which is the product of guanine oxidized at C8. The properties of 20 oxidative base pairs which contains Fapy-G were investigated via quantum chemistry methods. All model molecular structures were optimized with B3LYP/6-31 ＋G method and the frequency calculations were carried out to confirm that all the structures obtains were geometrically stable. The energies were determined at the MP2/ aug-cc-pVDZ level with BSSE corrections. The calculation results show that N7, N9 became hydrogen bond donor from accepter. Natural atomic charge of NT, N9 and 06 get more negative. The ability of 06 as H-bond donor enhanced. The bond lengths of C5--N7 and N7--C8 were increased by O. 0045 and 0. 0063 nm, C4--N9 was decreased by 0. 0015 nm. Compared with bases monomers, natural atomic charge of proton acceptors in hydrogen bond complexes increased by 0.05 e averagely, which is 8% of the original charge; natural atomic charges for proton donors have a decrease of 0. 02 e, which is 4% of the original charge. Com- pared with Fapy-G, when the N atom in Fapy-G six-membered ring was formed H-bond, the ring breathing and N-para-C vibrational frequencies were blue shifts. The vibrational frequencies were related to H-bond red shifts in all the base pairs. NH---N is stronger than NH---O in all the base pairs and in NH..-N the hydrogen bond energy of donor N atom in six-membered ring are bigger than donor N atom in NH： or open-ring. When Fapy-G pairs with base A, the binding energy region order is 1 〉2〉4〉3. When Fapy-G pairs with base T（R） , the binding energy region order is 3 = 4〉 1 〉2. In water solvent, the binding energies of Fapy-G pairs with base C reduced to 41.84--58.58 kJ/mol, and the order of the binding energy was changed.