Capturing Transient Endoperoxide in the Singlet Oxygen Oxidation of Guanine. Issue 9 (27th January 2016)

• Record Type: Journal Article
• Authors: Lu, Wenchao; Liu, Jianbo
• Is Part Of: Chemistry. Volume 22:Issue 9(2016)
• Page Start: 3127
• Page End: 3138
• Publication Date: 2016-01-27
• Subjects: density functional calculations -- ion–molecule reactions -- mass spectrometry -- molecular dynamics -- singlet oxygen; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201504140
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Tracing DNA damage : Transient endoperoxide, which initiates the singlet O2 induced lesion of the guanine base of DNA, can be captured in gas‐phase ion–molecule collision mass spectrometry (see figure). Experiments, corroborated by results from kinetic modeling and dynamics simulations, provide information about early‐stage dynamics of guanine oxidation that is missing from conventional condensed‐phase studies.