Mechanism on Damage of the Purine Base in a Nucleic Acid Using the Electrogenerated Active Oxygen

活性氧在体内产生，伴随着从突变物质中衍生的活化自由基。从这一观点来看，活性氧的突变特性引起了相当大的兴趣。在这项工作中，我研究了鸟苷衍生物与电生成的超氧阴离子自由基相互作用对核酸嘌呤碱基损伤的机制。氧在DMF中的可逆循环伏安图证明在鸟苷存在下是不可逆的。这不是由超氧阴离子自由基介导的单电子转移引起的，而是由EC机制引起的。通过光谱电化学和色谱测定，确定了反应产物为鸟嘌呤及其在嘌呤碱基中的类似物。一个质子从鸟苷转移到电生成的超氧阴离子自由基，导致氢氧自由基。鸟嘌呤的生成是由过氧化氢引起的，过氧化氢是由羟基自由基歧化反应产生的。鸟苷似乎与氢氧自由基反应，产生嘌呤碱中受损的产物。分子轨道计算部分支持这些结论。研究发现，核酸中嘌呤碱基破坏的关键反应是质子从鸟苷转移到超氧阴离子自由基。

Active oxygens are generated in a body, coupled with derivation of the activated free radical from mutation substances. From the point of view considerable interest is devoted to mutation character of the active oxygens. In this work, I have investigated the mechanism on damage of the purine base in a nucleic acid in terms of interaction of the guanosine derivative with electrogenerated superoxide anion radical.A reversible cyclic voltammogram of oxygen in DMF came out to be irreversible in the presence of guanosine. This arises from not a one-electron transfer mediated by superoxide anion radical but the EC mechanism. The reaction products are identified as guanine and its analog damaged in the purine base by the spectroelectrochemical and chromatographic measurements. A proton transfer from guanosine to electrogenerated superoxide anion radical leads to hydroperoxy radical. Generation of guanine is caused by hydrogen peroxide derived from the disproportionation reaction of hydroperoxy radical. It seems that guanosine reacts with hydroperoxy radical, yielding the product damaged in the purine base. Molecular orbital calculations partially support these conclusions. It has been found that the key reaction for the damage of the purine base in a nucleic acid is the proton transfer from guanosine to superoxide anion radical.