Theoretical Studies On The Reaction Mechanism Of Superoxide Radical And Singlet Oxygen Oxidative Damage To2’-deoxyguanosine

In this thesis, according to the basis of Density Functional Theory (DFT) at theB3LYP/6-31G(d, p) calculation level by Gaussian09proceeding, two kinds ofreaction mechanisms about superoxide anion radical and singlet oxygen oxidizing anddamaging2’-deoxyguanosine were studied respectively. The reactants, intermediates,transition states and products were optimized successively, the frequency analysiswas carried out, the energy and NBO charge were also calculated and analyzed toexplore the mechanism of the reaction. For the transition state, we use the method ofIntrinsic Reaction Coordinate (IRC) to describe the reaction path, further to ascertainthe correctness of the transition state. Finally, compared the reaction process of theactivation energy barrier, determine the correct reaction mechanism.This paper includes two main project contents as follows: the project one is theresearch about the reaction mechanism of superoxide anion radical as a free radicaloxidizing and damaging2’-deoxyguanosine to generate a series of importantintermediates, transition states and the final product2,2-diamino-4-[(2-deoxy-β-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone(dZ). We have designed two kindsof main reaction path:channel1and2; The difference between the two channels liesin the presence of H2O involved in the reaction or not. According to all aspects of thetwo reaction paths in the calculation and analysis of data, channel2is the optimalreaction channel. Because in the reaction, H2O as a medium of proton exchange,reduced the energy barrier, it is easier to form the transition state.The project two is the research about the reaction mechanism of singlet oxygenoxidizing and damaging2’-deoxyguanosine to generate a series of importantintermediates, transition states and the final products spiroiminodihydantoin: dSp(R)and dSp(S). According the conclusion of project one, H2O is involved in this reaction.Compared with the final product dSp(R) and dSp(S), we found that the structure ofdSp(R) is more stable and easier to generate than dSp(S), so the dSp(R) is the finalproduct, which corresponds with the experimental facts.