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.

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.