Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
J Phys Chem B. 2011 Mar 3;115(8):1911-7. doi: 10.1021/jp111059q. Epub 2011 Feb 4.
In the present study, we consider the formation of a single strand break (SSB) in DNA via an alternative mechanism involving O-P bond splitting that was observed as a minor route to DNA damage induced by low-energy electrons (LEEs) or γ radiation. We postulate and characterize, at the B3LYP/6-31++G(**) level, a path that starts with LEE attachment to the nucleotide of thymine resulting in a stable valence radical anion localized on pyrimidine. In the next step, a proton is attached to the C5 position of thymine, producing a neutral monohydroradical of this nucleotide. This event triggers the subsequent intramolecular transfer of a sugar hydrogen atom from C3' or C5' to the C6 site of thymine. In the final elemental reaction, O-P bond dissociation takes place, which yields the phosphoryl radical and a cyclic ketone or aldehyde. Identification of the latter species as well as 5,6-dihydropyrimidines in DNA solutions irradiated with ionizing radiation could provide experimental confirmation of the suggested mechanism.
在本研究中，我们考虑了一种通过涉及 O-P 键断裂的替代机制形成单链断裂 (SSB) 的情况，这种机制是通过低能电子 (LEE) 或 γ 辐射诱导 DNA 损伤的次要途径观察到的。我们假设并在 B3LYP/6-31++G(**) 水平上描述了一条从 LEE 附着到胸腺嘧啶核苷酸开始的途径，导致稳定的价自由基阴离子定位于嘧啶上。在下一个步骤中，质子附着到胸腺嘧啶的 C5 位置，产生该核苷酸的中性单氢自由基。这一事件触发了随后的糖氢原子从 C3' 或 C5' 到胸腺嘧啶的 C6 位点的分子内转移。在最后一个元素反应中，O-P 键解离发生，生成磷自由基和环状酮或醛。在离子辐射照射的 DNA 溶液中鉴定出后者以及 5,6-二氢嘧啶，可以为所提出的机制提供实验证实。
