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

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• 作者：Yan Sun ; Wenchao Lu ; Jianbo Liu
• 刊名：Journal of Physical Chemistry B
• 出版年：2017
• 出版时间：February 9, 2017
• 年：2017
• 卷：121
• 期：5
• 页码：956-966
• 全文大小：632K
• ISSN：1520-5207

文摘

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 (a¹Δ_g) 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 (E_col) on reaction cross sections over a center-of-mass E_col 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]⁺·W_0,1 (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 E_col 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]⁺·W_0,1 and [8-oxoG – H]⁻·W_0,1, which are relevant to the pH dependence of 8-oxoG oxidation in solution, are interpreted in terms of different ¹O₂ addition pathways.