Studies On The Reaction Mechanisms Of Singlet Oxygen Damage To2’-deoxyguanosine And8-oxo-deoxyguanosine

In this paper, density functional theory (DFT) calculations have been carried out to study the reaction mechanism of singlet oxygen as a free radical oxidative damage to DNA bases.The first one is the reaction mechanism on singlet oxygen oxidative damage to2’-deoxyguanosine.And the second one is the reaction mechanism of singlet oxygen damage to8-oxo-deoxyguanosine.The reaction mechanisms of singlet oxygen with2’-deoxyguanosine by the reaction of spiroiminodihydantoin was studied using density functional theory at the B3LYP/6-31G(d,p). The reaction mechanisms were found to consist of two stages.The first stages is the singlet oxygen attack from both sides of the2’-deoxy-guanosine (channels a and b) generate peroxide intermediates, This step is [4+2] cycloaddition. First, its charge is analysis by using the Natural Bond Orbital (NBO), and obtain cycloaddition react of the step [4+2] is polarized. Second,difference of two new bond lengths at transition states indicate that the [4+2] cycloadditions in this reaction are asynchronous processes. The second stages is the peroxide intermediates to produce the final product of were the two diastereomers of spiroiminodihydantoin via four possible channels(channels1,2,3and4).The calculated results revealed that the most energetically favorable path is channel4and found that dSp (R) is stable than dSp (S). which is consistent well with the experiment.The second topic is the reaction mechanism of singlet oxygen damage to8-oxo-deoxyguanosine was studied. In this topic, First,we using the density functional investigated the syn (anti)-8-oxo-deoxyguanosine enol tautomerism. We have designed two paths (Channel1and Channel2), the difference of Channel1and Channel2is adding H2O molecule in Channel2. The calculated results revealed that the most energetically favorable path is channel2. That the H2O molecule during the reaction as a proton exchange medium, accelerate the reaction process.Second,the reaction mechanism8-oxo-deoxyguanosine with singlet oxygen was studied using density functional theory. The singlet oxygen attack from both sides of the8- oxo-deoxyguanosine (Channel3and4) generate peroxide intermediates, this step is [2+2] cycloaddition reaction,difference of two new bond lengths at transition states indicate that the [2+2] cycloadditions in this reaction are asynchronous processes.Then the reaction along these two channels to generate spiroiminodihydantoin.Howere,in this process has a light reaction.That need to use the excited state to find the transition states. Currently,this step of the calculation are still fumbling.For the dSp (R) and dSp (S), dSp (R) is relatively stable,which agrees with the experiment.