摘要/Abstract
由于8-氮杂鸟嘌呤（8-AG）的氧化还原电势比鸟嘌呤（G）更低，所以单电子氧化嵌有8-AG的DNA后，空穴最终会被8-AG捕获形成8-氮杂鸟嘌呤自由基阳离子（8-AG·+）.因为酸性的急剧增强，8-AG·+一般会发生脱质子反应.在本工作中，在M06-2X/6-31+G（d）理论水平，使用显性水分子和连续溶剂化模型模拟8-AG·+的溶剂化效应，对其脱亚氨基质子（N（1）-H）反应进行了研究.发现位于8-AG·+中N（1）-H、O（6）、N（2）-H附近以及在O（6）水分子附近稍微远离8-AG·+的4个水分子会对8-AG·+脱质子反应产生重要影响，质子从8-AG·+传递到溶液中具有方向性；最后，通过进一步在N（2）-H、N（3）、O（6）、N（7）和N（8）等位点附近添加水分子（9H2O）得到了更加精确的8-AG·+脱质子反应能垒（19.5 kJ/mol）.
关键词: 8-氮杂鸟嘌呤, 单电子氧化, 脱质子反应, 势能面
Due to the lower redox potential comparing with guanine, it is the 8-azaguanine (8-AG) as the hole trap to form 8-azaguanine radical cation (8-AG·+) after one-electron oxidation of DNA containing 8-azaguanine. In generally, the 8-AG·+ may suffer from deprotonation to generate 8-AG(-H)·. In this text, we were stimulated to investigate the deprotonation reaction of 8-AG·+ generating by one-electron oxidation at M06-2X/6-31+G(d) level with explicit water molecules and polarized continuum model (PCM) to simulate the solvent effect. By building deprotonation model with different number of explicit water molecules, we found that these four water molecules locating around N(1)-H, O(6), N(2)-H of 8-AG·+ as well as the one locating in the second water shell which was hydrogen-bonding with the water around O(6) were necessary. If the water in the second water shell was not included, the imino proton (N(1)-H) would not transfer into the bulk water. In parallel, the N(1)-H would transfer to the O(6) of 8-AG·+ by intramolecular proton transfer. If the water molecule locating around N(2)-H was removed, the 8-AG·+ deprotonation would continue but the energy barrier would be lowered from 24.8 kJ/mol to 16.3 kJ/mol. In addition, the site of the water molecule in the second water shell was also studied. If putting the water in the second water shell around N(2)-H of 8-AG·+, the proton would be stabilized between the N(1) of 8-AG·+ and the oxygen of water molecule around N(1)-H meaning the proton would not be transferred into bulk water. Further, in order to test the influence of water number on 8-AG·+ deprotonation, the fifth water molecule, which is hydrogen-bonding with the water molecule around N(2)-H and another N(2)-H, was added. The potential energy surface with 5H2O revealed that it is almost no effect on the deprotonation pathway and energy barrier (25.5 kJ/mol). Lastly, so as to obtain the exact energy barrier of 8-AG·+ deprotonation, the deprotonation model with more explicit water molecules (9H2O) was proposed, where the additional water molecules were placed around N(2)-H, N(3), O(6), N(7) and N(8). From the potential energy surface, the deprotonation energy barrier of 8-AG·+ was confirmed to be 19.5 kJ/mol. These theoretical results provide valuable dynamics information and mechanistic insights for further understanding the properties of nucleic acid base analogues and one-electron oxidation of DNA.
Key words: 8-azaguanine, one-electron oxidation, deprotonation reaction, potential energy surface
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