首页|氢键对羟基自由基与鸟嘌呤反应影响的理论研究

氢键对羟基自由基与鸟嘌呤反应影响的理论研究

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羟基自由基(·OH)是一种有代表性的活性氧物质(ROS),可与DNA分子反应导致DNA损伤.研究结果表明,·OH与鸟嘌呤(G)反应具有氢键依赖特性,反平行三链中G碱基氢键环境与已报道的体系不同,且更复杂,可能导致反平行三链中·OH与G碱基衰变反应不同.基于此,本文选取反平行三链碱基对GGC为模型,通过结构分析、最高占据轨道计算、构建C4,C5,C8加成和夺氨基氢(-H2)反应吉布斯自由能面等研究了氢键对G与·OH反应的影响.结果显示,·OH可与第三条链中的G碱基通过直接夺氢反应生成中性自由基G(-H2)·;C8加成自由基在O2参与时易生成8-oxoG,能垒低于夺氢路径,为主反应通道,但夺氢路径可与之竞争;此外,离子对中间体稳定性受氢键影响,在GGC碱基对中,羟基化自由基比离子对中间体更稳定.
Theoretical Studies of Effect of Hydrogen Bond on Reaction of Hydroxyl Radicals and Guanine
Hydroxyl radical(·OH)is a representative reactive oxygen species(ROS)with high oxidation potential,and could lead to the indiscriminate chemical modification on DNA causing oxidative damage.Interestingly,it has documented that the reaction of·OH and guanine(G)reveals hydrogen bond-dependent fashion.Due to the highly specific binding of triplex forming oligonucleotide(TFO)to target duplex DNA leading to various surroundings of G,it makes triplex DNA as a prototype model to be examined.Inspired by this,by selecting the building block of antiparallel triplex DNA-GGC motif as the substrate,a comprehensive theoretical investigation was performed to illuminate the influence of hydrogen bond on the obscure reaction of·OH and G by structural analysis,HOMO calculation and mapping the energy profiles for both addition and hydrogen abstraction reactions.Results reveal that the G located in TFO is more susceptible to the attack of·OH.In GGC base pair,the neutral radical G(-H2)·could be formed by direct H-abstraction,where the participation of explicit water is adverse to H-abstraction from N2 of G.The electrophilic attack of·OH to C8 of G resulting in 8-oxoG is the most favorable course due to the lowest energy barrier in comparison with H-abstraction pathway.And the stability of ion-pairs appears to significantly influence by hydrogen bond,which is less stable than the hydroxylated radicals different with free G.These results show clearly that the hydrogen bonds guide the reaction flux of·OH and G.

Hydroxyl radicalHydrogen bondAntiparallel triplex DNAAddition reactionHydrogen abstraction reaction

王英辉、薛浩明、马斌、李宗璇、马亚婷、马蕾、魏思敏

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长安大学理学院,西安 710064

建筑工程学院,西安 710064

公路学院,西安 710064

陕西中医药大学,陕西中药资源产业化省部共建协同创新中心,咸阳 712083

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羟基自由基 氢键 反平行三链DNA 加成反应 夺氢反应

国家自然科学基金国家自然科学基金陕西省青年科技新星项目陕西省重点研发计划项目陕西省重点研发计划项目西安市科技计划项目陕西中医药大学2023年度科技创新人才体系建设计划项目大学生创新创业训练计划项目陕西省自然科学基础研究计划项目

22103007822743532023KJXX-0632024SF-YBXM-5172024SF-YBXM-42622GXFW01532023-LJRC-03S2023107102212024JC-YBQN-0586

2024

10.7503/cjcu20240208

高等学校化学学报
中华人民共和国教育部委托 吉林大学和南开大学

高等学校化学学报

CSTPCD北大核心
影响因子：1.067
ISSN：0251-0790
年,卷(期)：2024.45(8)
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