Reaction mechanism and dynamics for C8-hydroxylation of 9-methylguanine radical cation by water molecules
Reaction mechanism and dynamics for C8-hydroxylation of 9-methylguanine radical cation by water molecules
复制标题
水分子对9-甲基鸟嘌呤自由基阳离子C8-羟基化的反应机理和动力学
DOI：
10.1039/d1cp03884b
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发表时间：
2021
影响因子：
3.3
通讯作者：
Liu, Jianbo
中科院分区：
文献类型：
--
作者：
Zhou, Wenjing;Liu, Jianbo
与水溶液中的自发去质子化相反，鸟嘌呤和鸟苷自由基阳离子与气相中的水的反应完全是通过自由基阳离子的水合引发的，正如最近的工作所报道的那样（Y. Sun等人, Phys. Chem. Chem. Phys., 2018, 20, 27510）。由于气相水合反应与双链 DNA 中鸟嘌呤自由基阳离子的实际情况非常相似，因此探索其水复合物内的后续反应可以深入了解由此产生的核苷氧化损伤。本文通过引导离子束质谱实验和直接动力学轨迹模拟来研究气相中9-甲基鸟嘌呤自由基阳离子与一个和两个水配体（即9MG˙+·(H2O)1-2）的原型配合物，其中配合物在实验中通过碰撞激活而在模拟中通过高温热激发被激活。在质谱测量、轨迹结果和反应势能表面的指导下，确定了三种反应途径。前两条反应途径从 9MG˙+ 中的 O6 和 N7 原子从水中夺取 H 原子开始，分别称为 HAO6 和 HAN7。 HAO6 和 HAN7 反应的主要产物，包括 [9MG + HO6]+/[9MG + HN7]+ 和 ˙OH，通过 C8-羟基化进一步反应形成 [8OH-9MG + HO6]˙+ 和 [8OH-9MG + HN7]˙+ 或形成 6-烯醇-鸟嘌呤 (6-enol-G˙+) 和 7H-鸟嘌呤 (7HG˙+) 的自由基阳离子通过SN2型甲醇消除。第三条反应途径对应于通过从络合物中消除H形成8OH-9MG+，称为HE。在这些产物通道中，[8OH-9MG + HN7]˙+ 具有最有利的形成概率，特别是在存在额外水分子的情况下。该产品可能作为 DNA 中 8-oxo-7,8-二氢鸟嘌呤损伤的前置结构，并且对辐射暴露和放射治疗的健康影响具有影响。
In contrast to their spontaneous deprotonation in aqueous solution, reactions of guanine and guanosine radical cations with water in the gas phase are exclusively initiated by hydration of the radical cations as reported in recent work (Y. Sun et al., Phys. Chem. Chem. Phys., 2018, 20, 27510). As gas-phase hydration reactions closely mimic the actual scenario for guanine radical cations in double-stranded DNA, exploration of subsequent reactions within their water complexes can provide an insight into the resulting oxidative damage to nucleosides. Herein guided-ion beam mass spectrometry experiment and direct dynamics trajectory simulations were carried out to examine prototype complexes of the 9-methylguanine radical cation with one and two water ligands (i.e., 9MG˙+·(H2O)1–2) in the gas phase, wherein the complexes were activated by collisional activation in the experiment and by thermal excitation at high temperatures in the simulations. Guided by mass spectroscopic measurements, trajectory results and reaction potential energy surface, three reaction pathways were identified. The first two reaction pathways start with H-atom abstraction from water by the O6 and N7 atoms in 9MG˙+ and are referred to as HAO6 and HAN7, respectively. The primary products of HAO6 and HAN7 reactions, including [9MG + HO6]+/[9MG + HN7]+ and ˙OH, react further to either form [8OH-9MG + HO6]˙+ and [8OH-9MG + HN7]˙+via C8-hydroxylation or form radical cations of 6-enol-guanine (6-enol-G˙+) and 7H-guanine (7HG˙+) via SN2-type methanol elimination. The third reaction pathway corresponds to the formation of 8OH-9MG+ by H elimination from the complex, referred to as HE. Among these product channels, [8OH-9MG + HN7]˙+ has the most favorable formation probability, especially in the presence of additional water molecules. This product may serve as a preceding structure to the 8-oxo-7,8-dihydroguanine lesion in DNA and has implications for health effects of radiation exposure and radiation therapy.