Singlet O Reactions with Radical Cations of 8-Bromoguanine and 8-Bromoguanosine: Guided-Ion Beam Mass Spectrometric Measurements and Theoretical Treatments.

8-Bromoguanosine is generated in vivo as a biomarker for early inflammation. Its formation and secondary reactions lead to a variety of biological sequelae at inflammation sites, most of which are mutagenic and linked to cancer. Herein, we report the formation of radical cations of 8-bromoguanine (8BrG) and 8-bromoguanosine (8BrGuo) and their reactions toward the lowest excited singlet molecular oxygen (O)─a common reactive oxygen species generated in biological systems. This work aims to investigate synergistic, oxidatively generated damage of 8-brominated guanine and guanosine that may occur upon ionizing radiation, one-electron oxidation, and O oxidation. Capitalizing on measurements of reaction product ions and cross sections of 8BrG and 8BrGuo with O using guided-ion beam tandem mass spectrometry and augmented by computational modeling of the prototype reaction system, 8BrG + O, using the approximately spin-projected ωB97XD/6-31+G(d,p) density functional theory, the coupled cluster DLPNO-CCSD(T)/aug-cc-pVTZ and the multireference CASPT2(21,15)/6-31G**, probable reaction products, and potential energy surfaces (PESs) were mapped out. 8BrG and 8BrGuo present similar exothermic oxidation products, and their reaction efficiencies with O increase with decreasing collision energy. Both single- and multireference theories predicted that the two most energetically favorable reaction pathways correspond to O-addition to the C8 and C5-positions of 8BrG, respectively. The CASPT2-calculated PES represents the best quantitative agreement with the experimental benchmark, in that the oxidation exothermicity is close to the water hydration energy of product ions and, thus, is able to eliminate a water ligand in the product ions.