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-nucle-obase 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]+)* ⇌ (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.