title: Capturing Transient Endoperoxide in the Singlet Oxygen Oxidation of Guanine.
abstract: The chemistry of singlet O2 toward the guanine base of DNA is highly relevant to DNA lesion, mutation, cell death, and pathological conditions. This oxidative damage is initiated by the formation of a transient endoperoxide through the Diels-Alder cycloaddition of singlet O2 to the guanine imidazole ring. However, no endoperoxide formation was directly detected in native guanine or guanosine, even at -100 °C. Herein, gas-phase ion-molecule scattering mass spectrometry was utilized to capture unstable endoperoxides in the collisions of hydrated guanine ions (protonated or deprotonated) with singlet O2 at ambient temperature. Corroborated by results from potential energy surface exploration, kinetic modeling, and dynamics simulations, various aspects of endoperoxide formation and transformation (including its dependence on guanine ionization and hydration states, as well as on collision energy) were determined. This work has pieced together reaction mechanisms, kinetics, and dynamics data concerning the early stage of singlet O2 induced guanine oxidation, which is missing from conventional condensed-phase studies.
authors.affiliation: Department of Chemistry and Biochemistry, Queens College and the Graduate Center, of the City University of New York, 65-30 Kissena Blvd, Queens, NY, 11367, USA.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Chemistry and Biochemistry, Queens College and the Graduate Center, of the City University of New York, 65-30 Kissena Blvd, Queens, NY, 11367, USA. jianbo.liu@qc.cuny.edu.
authors.forename: Jianbo
authors.identifier: http://orcid.org/0000-0001-9577-3740
authors.initials: J
authors.lastname: Liu
mesh_terms: D061565:Cycloaddition Reaction; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006147:Guanine / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D007700:Kinetics; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D026082:Singlet Oxygen / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D026082:Singlet Oxygen; D006147:Guanine; D004247:DNA; D006861:Hydrogen Peroxide
keywords: density functional calculations; ion-molecule reactions; mass spectrometry; molecular dynamics; singlet oxygen