Electron spin, kinetic energy, and stereodynamics control of the reaction between 9-methyl-8-oxoguanine radical cation and nitric oxide.

8-oxoguanine (OG) is a prevalent DNA lesion and exhibits a significantly lower oxidation potential than natural nucleic acid components, making the formation of OG•+ radical cation the most efficient hole trap in the one-electron oxidation of DNA. Nitric oxide (•NO) is a precursor to reactive nitrogen species and plays multiple roles in biological activities, including DNA base nitrosation and enhancement of DNA radiosensitivity in radiotherapy. Herein, we report the reaction of •NO with 9-methyl-8-oxoguanine radical cation (9MOG•+), a model compound for OG•+ nucleoside. 9MOG•+ was generated via redox dissociation of [CuII(9MOG)3]•2+ and its reaction with •NO was investigated using electrospray ionization guided-ion beam mass spectrometry as a function of kinetic energy. Multiple coupled reaction potential energy surfaces were computed using spin-projected ωB97XD, DLPNO-CCSD(T), and CASPT2 methods, with theoretical results benchmarked against experimentally determined reaction thermodynamics. The synergistic experiment and computation revealed distinct reaction mechanisms and dynamics across the open-shell singlet, close-shell singlet, and triplet states formed in radical-radical collisions. Comparison with the reaction of •NO with guanine radical cation (G•+) [Benny and Liu, J. Chem. Phys. 159, 085102 (2023) and Benny et al., J. Chem. Phys. 161, 125101 (2024)] addressed the resemblances and distinctions between •NO reaction dynamics with OG•+ vs G•+. On the one hand, both systems present spin-orbit charge transfer, forming vibrationally excited NO+(ν+ = 1) product ions. On the other hand, OG•+ demonstrates lower nitrosation efficiency than G•+ due to few pathways, less favorable thermodynamics, and constrained stereodynamics. Only the closed-shell singlet [5-NO-9MOG]+ product was detected. This study provides new insights into •NO-mediated DNA damage.