8-Oxo-2'-deoxyguanosine (OG) is the most common nucleobase product formed under oxidative stress and therefore a biomarker for oxidatively generated DNA damage. The formation of OG and its secondary damage result in mutation and apoptosis and is implicated in photodynamic therapy for cancer. Compared to natural guanine, adenine, cytosine and thymine nucleobases, OG has the lowest adiabatic ionization energy. This makes OG a primary target upon photooxidation and ionizing radiation, leading to facile formation of OG radical cations. Of relevance to OG-mediated DNA lesions is singlet O2-induced damage. This study focused on the reaction of the radical cation of OG with electronically excited singlet O2, and provided a molecular-level description for the concurrent ionizing radiation damage and singlet O2 oxidation of DNA nucleobases. The formation of OG radical cation was realized in the gas phase by electrospray ionization (ESI) guided-ion-beam tandem mass spectrometry. The reaction of OG radical cation and singlet O2 was examined by the measurement of reaction product ions and cross sections as a function of collision energy from which reaction thermodynamics was measured. The major challenges of this reaction are first, the reaction complex produce two different doublet states and one quartet state in which the correct doublet state has higher energy than the one that is closer to the quartet state, and secondly, the multiconfigurational characters of the reaction structures arise from the mixed open- and closed-shell of singlet oxygen reactant. Guided by experiment and thermodynamics measurement, this study benchmarked various single- and multi-reference electronic structure theories and pinpointed the thermodynamically most favorable C5-O2 addition.

Singlet O2 oxidation of 8-Oxo-2'-deoxyguanosine radical cation: Using guided-ion beam tandem mass spectrometry and multi-reference computational methods

ACS Spring 2022

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