Insights into the Mechanism of Hydroxyl Radical Mediated Oxidations of 2-Aminopurine: A Computational and Sonochemical Product Analysis Study.

Prasanthkumar, Kavanal P; Rayaroth, Manoj P; Alvarez-Idaboy, Juan Raúl

Mechanistic details of hydroxyl radical (●OH) mediated oxidations of 2-aminopurine (2AP) in aqueous phase have been established in this study via a combination of DFT calculations (at M05-2X/6-311+G(d,p) level with SMD solvation) and end product analyses by LC-Q-TOF/MS method. Rate constants and branching ratios for single electron transfer (SET), two H-abstractions (HA) and seven radical adduct formation (RAF) reactions of ●OH with 2AP were evaluated using transition state theory (TST). The RAF at C8-position of 2AP is noted as the dominant process, which constitute almost 46.1% of overall reaction routes. The SET mechanism accounts for the second major pathway (39.6%) followed by RAF at C6-position (14.3%). Qualitative profiling of transformation products (TPs, i.e. the non-radical end products) of ●OH (formed via sonochemical method) reactions of 2AP by LC-Q-TOF/MS technique has demonstrated the formations of 14 molecular species. Among the 14 TPs (designated as TP1 to TP14), the lowest and highest mass to charge ratio (m/z) were respectively observed at 129 and 269 in ESI-MS positive ionization mode. The identities of all TPs have been proposed on the basis of elemental composition of [M+H]+ ions and their respective MS-MS fragments. Four TPs (including guanine) are considered as obtained directly from primary transients by radical elimination, radical-radical combination/disproportionation reactions. Formations of other 10 TPs are postulated as result of successive self- and/or cross-reactions of primary transients/four first generation TPs with reagents such as ●OH, O2 and solvent H2O molecules.