Low-energy electron attachment to 5′-thymidine monophosphate:: Modeling single strand breaks through dissociative electron attachment
Low-energy electron attachment to 5′-thymidine monophosphate:: Modeling single strand breaks through dissociative electron attachment
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DOI：
10.1021/jp070800x
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发表时间：
2007-05-17
影响因子：
3.3
通讯作者：
Sevilla, Michael D.
中科院分区：
文献类型：
--
作者：
Kumar, Anil;Sevilla, Michael D.
用密度泛函理论处理DNA的一个简单模型，即5‘-胸苷单磷酸(5’-dTMPH)，研究了低能电子(Lee)附着和随后的单链断裂(SSB)的形成机制。在本研究中，利用B3LYP泛函和6-31G*和6-31++G**基组，沿着绝热和垂直(电子附着在中性分子的优化几何构型上)阴离子表面，跟踪了Lee键引起的C-5‘-O-5’键解离。令人惊讶的是，发现阴离子自由基中C-5‘-O-5’键解离的势垒在绝热和垂直路径上几乎相同。这些结果支持这样的假设，即中性分子的虚拟分子轨道上的瞬时结合电子(形状共振)可能在DNA中糖-磷酸C-5‘-O-5’键的断裂中起关键作用，导致直接形成单链断裂，而没有明显的分子松弛。为了考虑溶剂化效应，我们考虑了5‘-DTMP被5个或11个水分子包围的中性和阴离子自由基，其中Na+是反离子。用B3LYP/6-31G**理论水平对这些结构进行了优化。我们发现5‘-DTMP阴离子自由基在水环境中绝热C-5’-O-5‘键解离的势垒高度明显高于在气相中的势垒高度，因此绝热途径不会对水相体系中的DNA链断裂有贡献。这一结果与实验结果相吻合。
Mechanisms of low-energy electron (LEE) attachment and subsequent single-strand break (SSB) formation are investigated by density functional theory treatment of a simple model for DNA, i.e., the nucleotide, 5'-thymidine monophosphate (5'-dTMPH). In the present study, the C-5'-O-5' bond dissociation due to LEE attachment has been followed along the adiabatic as well as on the vertical (electron attached to the optimized geometry of the neutral molecule) anionic surfaces using B3LYP functional and 6-31G* and 6-31++G** basis sets. Surprisingly, it is found that the PES of C-5'-O-5' bond dissociation in the anion radicals have approximately the same barrier for both adiabatic and vertical pathways. These results provide support for the hypothesis that transiently bound electrons (shape resonances) to the virtual molecular orbitals of the neutral molecule likely play a key role in the cleavage of the sugar-phosphate C-5'-O-5' bond in DNA resulting in the direct formation of single strand breaks without significant molecular relaxation. To take into account the solvation effects, we considered the neutral and anion radical of 5'-dTMP surrounded by 5 or 11 water molecules with Na+ as a counterion. These structures were optimized using the B3LYP/6-31G** level of theory. We find the barrier height for adiabatic C-5'-O-5' bond dissociation of 5'-dTMP anion radical in aqueous environment is so substantially higher than in the gas phase that the adiabatic route will not contribute to DNA strand cleavage in aqueous systems. This result is in agreement with experiment.