Gu Jiande, Xie Yaoming, Schaefer Henry F
Drug Design & Discovery Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, CAS, Shanghai 201203, PR China.
J Am Chem Soc. 2005 Jan 26;127(3):1053-7. doi: 10.1021/ja0400990.
DNA damage by attachment of low-energy secondary electrons is a very interesting and important mechanism. Electron capture and subsequent base release are thought to be the elementary steps of this mechanism. The process of the N1-glycosidic bond breaking of anion radicals of pyrimidine nucleosides, specifically the 2'-deoxyribothymidine (dT) and 2'-deoxyribocytidine (dC) anions, has been investigated theoretically at the B3LYP/DZP++ level of theory. The release of nucleobases by the attachment of low-energy electrons depends on the formation of a stable anion radical of the nucleoside. The lower bond-breaking activation energy and the higher vertical electron detachment energy for dT enables the heterolytic cleavage of the N1-glycosidic bond. However, with the higher bond-breaking activation energy and the lower vertical electron detachment energy for dC, the release of cytosine might be impractical when the incident electrons have high kinetic energy. Furthermore, the release of cytosine would have a quantum yield much lower than that of dT when the incident electrons have lower kinetic energy. This study also demonstrates the importance of the proton at O5' of 2'-deoxyribose in the base release process. Extending this investigation from dT to dC advances the insight into the mechanism of the N1-glycosidic bond-breaking process. The information from this extensive investigation should be valuable for further experimental studies of cytosine release in irradiated DNA.
低能二次电子附着导致的DNA损伤是一种非常有趣且重要的机制。电子捕获及随后的碱基释放被认为是该机制的基本步骤。在理论水平B3LYP/DZP++上，对嘧啶核苷阴离子自由基，特别是2'-脱氧胸苷（dT）和2'-脱氧胞苷（dC）阴离子的N1-糖苷键断裂过程进行了理论研究。低能电子附着导致的碱基释放取决于核苷稳定阴离子自由基的形成。dT较低的键断裂活化能和较高的垂直电子脱离能使得N1-糖苷键能够进行异裂。然而，dC具有较高的键断裂活化能和较低的垂直电子脱离能，当入射电子具有高动能时，胞嘧啶的释放可能不切实际。此外，当入射电子具有较低动能时，胞嘧啶的释放量子产率将远低于dT。该研究还证明了2'-脱氧核糖O5'位质子在碱基释放过程中的重要性。将该研究从dT扩展到dC，加深了对N1-糖苷键断裂过程机制的理解。这项广泛研究所得出的信息对于进一步开展辐照DNA中胞嘧啶释放的实验研究应具有重要价值。
