Exploration of the Singlet O2 Oxidation of 8-Oxoguanine by Guided-Ion Beam Scattering and Density Functional Theory: Changes of Reaction Intermediates, Energetics, and Kinetics upon Protonation/Deprotonation and Hydration.
Exploration of the Singlet O2 Oxidation of 8-Oxoguanine by Guided-Ion Beam Scattering and Density Functional Theory: Changes of Reaction Intermediates, Energetics, and Kinetics upon Protonation/Deprotonation and Hydration.
复制标题
通过引导离子束散射和密度泛函理论探索 8-氧代鸟嘌呤的单线态 O2 氧化：质子化/去质子化和水合时反应中间体、能量和动力学的变化。
DOI：
10.1021/acs.jpcb.6b11464
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Jianbo Liu
中科院分区：
文献类型：
--
作者：
Yan Sun;Wenchao Lu;Jianbo Liu
8-氧-7，8-二氢-2‘-脱氧鸟苷(8-oxodGuo，8-oxodGuo)是由活性氧和电离辐射引起的最常见的DNA损伤之一，参与诱变、致癌和细胞死亡。值得注意的是，8-oxodGuo对单态(A1Δg)O2的反应比未损伤的鸟苷更敏感，8-oxodGuo二次氧化引起的损伤更具诱变性。本文研究了游离碱8-氧鸟嘌呤(8-oxoG)在不同初始条件下的氧氧化反应，包括质子化的[8-oxoG+H]+、去质子化的[8-oxoG-H]-及其一水合物。实验在导离子束散射串联质谱计上进行。测量包括碰撞能(ECOL)对质量中心ECOL范围内反应截面的影响，范围从0.1 eV到0.5 eV。本研究的目的是定量探讨8-oxoG氧化的早期阶段对电离和水合的敏感性。通过密度泛函理论和莱斯-拉姆斯佩格-卡塞尔-马库斯计算，确定了反应路径上的中间体和产物，确定了可获得的反应势能面，并从能量和动力学的角度对反应结果进行了合理化。在[8-oxoG+H]+·W0，1(W=H2O)反应中没有观察到产物，因为不可逾越的障碍阻碍了1O2加成到反应物离子上。在这种情况下，也没有[8-oxoG-H]-与1O2反应，这是因为瞬时中间体迅速衰减为起始反应物。然而，[8-oxoG-H]-的非反应性被水合作用逆转，结果捕获了[8-oxoG-H]-的4，5-二氧杂环己烷作为主要的氧化产物。[8-oxoG-H]-·W+1O2的反应截面随着乙醇值的增加而减小，在0.3 eV以上可以忽略不计，表明该反应是放热的，在反应物上方没有势垒。用不同的1O2加成途径解释了[8-oxoG+H]+·W0，1和[8-oxoG-H]-·W0，1在溶液中的氧化行为与溶液中8-oxoG氧化的pH依赖性有关。
8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) is one of the most common DNA lesions resulting from reactive oxygen species and ionizing radiation, and is involved in mutagenesis, carcinogenesis, and cell death. Notably, 8-oxodGuo is more reactive toward singlet (a1Δg) O2 than the undamaged guanosine, and the lesions arising from the secondary oxidation of 8-oxodGuo are more mutagenic. Herein the 1O2 oxidation of free base 8-oxoguanine (8-oxoG) was investigated at different initial conditions including protonated [8-oxoG + H]+, deprotonated [8-oxoG - H]-, and their monohydrates. Experiment was carried out on a guided-ion beam scattering tandem mass spectrometer. Measurements include the effects of collision energy (Ecol) on reaction cross sections over a center-of-mass Ecol range from 0.1 to 0.5 eV. The aim of this study is to quantitatively probe the sensitivity of the early stage of 8-oxoG oxidation to ionization and hydration. Density functional theory and Rice-Ramsperger-Kassel-Marcus calculations were performed to identify the intermediates and the products along reaction pathways and locate accessible reaction potential energy surfaces, and to rationalize reaction outcomes from energetic and kinetic points of view. No product was observed for the reaction of [8-oxoG + H]+·W0,1 (W = H2O) because insurmountable barriers block the addition of 1O2 to reactant ions. Neither was [8-oxoG - H]- reactive with 1O2, in this case due to the rapid decay of transient intermediates to starting reactants. However, the nonreactivity of [8-oxoG - H]- was inverted by hydration; as a result, 4,5-dioxetane of [8-oxoG - H]- was captured as the main oxidation product. Reaction cross section for [8-oxoG - H]-·W + 1O2 decreases with increasing Ecol and becomes negligible above 0.3 eV, indicating that the reaction is exothermic and has no barriers above reactants. The contrasting oxidation behaviors of [8-oxoG + H]+·W0,1 and [8-oxoG - H]-·W0,1, which are relevant to the pH dependence of 8-oxoG oxidation in solution, are interpreted in terms of different 1O2 addition pathways.
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影响因子：
5.2
作者：
J. Niles;J. Wishnok;S. Tannenbaum
通讯作者：
J. Niles;J. Wishnok;S. Tannenbaum
影响因子：
6
作者：
Zhang, J;Perry, G;Montine, TJ
通讯作者：
Montine, TJ
影响因子：
2.9
作者：
Henderson, PT;Delaney, JC;Essigmann, JM
通讯作者：
Essigmann, JM
影响因子：
--
作者：
Lovell, MA;Markesbery, WR
通讯作者：
Markesbery, WR