Singlet Oxygen Oxidation of the Radical Cations of 8‐Oxo‐2′‐deoxyguanosine and Its 9‐Methyl Analogue: Dynamics, Potential Energy Surface, and Products Mediated by C5‐O2‐Addition.

8‐Oxo‐2′‐deoxyguanosine (OG) is the most common DNA lesion. Notably, OG becomes more susceptible to oxidative damage than the undamaged nucleoside, forming mutagenic products in vivo. Herein the reactions of singlet O2 with the radical cations of 8‐oxo‐2′‐deoxyguanosine (OG.+) and 9‐methyl‐8‐oxoguanine (9MOG.+) were investigated using ion‐molecule scattering mass spectrometry, from which barrierless, exothermic O2‐addition products were detected for both reaction systems. Corroborated by static reaction potential energy surface constructed using multi‐reference CASPT2 theory and molecular dynamics simulated in the presence of the reactants′ kinetic and internal energies, the C5‐terminal O2‐addition was pinpointed as the most probable reaction pathway. By elucidating the reaction mechanism, kinetics and dynamics, and reaction products and energetics, this work constitutes the first report unraveling the synergetic damage of OG by ionizing radiation and singlet O2. [ABSTRACT FROM AUTHOR]