title: Exploration of the Singlet O2Oxidation of 8-Oxoguanine by Guided-Ion Beam Scattering and Density Functional Theory: Changes of Reaction Intermediates, Energetics, and Kinetics upon Protonation/Deprotonation and Hydration.
abstract: 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) O2than the undamaged guanosine, and the lesions arising from the secondary oxidation of 8-oxodGuo are more mutagenic. Herein the1O2oxidation 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 Ecolrange 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 of1O2to reactant ions. Neither was [8-oxoG - H]-reactive with1O2, 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 +1O2decreases with increasing Ecoland 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]+·W0,1and [8-oxoG - H]-·W0,1, which are relevant to the pH dependence of 8-oxoG oxidation in solution, are interpreted in terms of different1O2addition pathways.
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of the City University of New York , 65-30 Kissena Blvd., Queens, New York 11367, United States.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York , 365 Fifth Ave., New York, New York 10016, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of the City University of New York , 65-30 Kissena Blvd., Queens, New York 11367, United States.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York , 365 Fifth Ave., New York, New York 10016, United States.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of the City University of New York , 65-30 Kissena Blvd., Queens, New York 11367, United States.|Ph.D. Program in Chemistry, The Graduate Center of the City University of New York , 365 Fifth Ave., New York, New York 10016, United States.
authors.forename: Jianbo
authors.identifier: 0000-0001-9577-3740
authors.initials: J
authors.lastname: Liu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D011522:Protons; D011789:Quantum Theory; D014867:Water / Q000737:chemistry*
chemical_list: D011522:Protons; D014867:Water; C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010100:Oxygen