Development of a Double-Well Potential upon Collisional Activation that Facilitates Proton Transfer in 9-Methyl-8-oxoguanine–9-Methyladenine Base-Pair Radical Cation^†

8-Oxoguanine (OG) is the most common oxidatively generated nucleobase damage and can mispair with adenine (A) in Hoogsteen mode during replication. Besides introducing the G·C→T·A transversion mutation, the OG·A base pair is vulnerable to ionizing radiation and one-electron oxidation owing to the lower ionization and oxidation potentials of OG than natural DNA nucleobases. Herein, we report the formation and collision-induced dissociation (CID) of the radical cation of a model base pair consisting of nucleoside-mimicking 9-methyl-8-oxoguanine (9MOG) and 9-methyladenine (9MA). The 9MOG·9MA^•+ radical cation is formed in the gas phase by redox-separation of electrospray ionization-produced Cu^II-nucleobase complexes, and its CID is examined using guided-ion beam tandem mass spectrometry. Measurement included kinetic energy-dependent dissociation product ions and cross sections, from which the product pairs of 9MOG – H^• + 9MA+H⁺ (major dissociation channel) and 9MOG^•+ + 9MA (minor) were detected with 0 K dissociation threshold energies of 1.8 and 1.65 eV, respectively. The 9MOG·9MA^•+ structures were examined using density functional theory, and important conformations were all featured by complete intra-base pair proton transfer as 9MOG – H^•·9MA+H⁺. On the other hand, the production of 9MOG^•++9MA in dissociation required a 9MOG^•+·9MA intermediate. The results were rationalized by the discovery of a double-well potential that evolves on the reaction potential energy surface of the collisionally activated base pair, leading to the proton-transfer equilibrium of excited (9MOG – H^•·9MA+H⁺)* \rightleftharpoons (9MOG^•+·9MA)*. The combined experimental and theoretical work provides insight into the less intuitive aspects of this biologically-important, non-canonical base pair, especially its opening upon oxidative and ionization damage.