Glycosidic bond cleavage of pyrimidine nucleosides by low-energy electrons: A theoretical rationale
Glycosidic bond cleavage of pyrimidine nucleosides by low-energy electrons: A theoretical rationale
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DOI：
10.1021/ja0400990
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发表时间：
2005-01-26
影响因子：
15
通讯作者：
Schaefer, HF
中科院分区：
文献类型：
--
作者：
Gu, JD;Xie, YM;Schaefer, HF
低能二次电子对DNA的损伤是一种非常有趣和重要的机制。电子捕获和随后的碱释放被认为是这一机制的基本步骤。在B3LYP/ dzp++的理论水平上研究了嘧啶核苷阴离子自由基，特别是2'-脱氧核糖苷（dT）和2'-脱氧核糖苷（dC）阴离子的n1 -糖苷键断裂过程。低能电子的附着释放核碱基取决于核苷稳定阴离子自由基的形成。dT较低的断键活化能和较高的垂直电子脱离能使n1 -糖苷键发生异裂解。然而，由于dC的断键活化能较高，而垂直电子脱离能较低，因此当入射电子具有高动能时，可能无法实现胞嘧啶的释放。此外，当入射电子的动能较低时，胞嘧啶的释放量子产率远低于dT。本研究也证明了2′-脱氧核糖的O5′处质子在碱释放过程中的重要性。将这一研究从dT扩展到dC，进一步深入了解了n1 -糖苷断键过程的机制。这项广泛调查的信息对辐照DNA中胞嘧啶释放的进一步实验研究有价值。
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.