Oxidation of 2'-Deoxyguanosine 5'-Monophosphate Photoinduced by Pterin: Type Ⅰ versus Type Ⅱ Mechanism

摘要

UV-A radiation (320-400 nm) induces damage to the DNA molecule and its components through different photosensitized reactions. Among these processes, photosensitized oxidations may occur through electron transfer or hydrogen abstraction (type Ⅰ) and/or the production of singlet molecular oxygen (~1O_2) (type Ⅱ). Pterins, heterocyclic compounds widespread in biological systems, participate in relevant biological processes and are able to act as photosensitizers. We have investigated the photosensitized oxidation of 2'-deoxyguanosine 5'-monophosphate (dGMP) by pterin (PT) in aqueous solution under UV-A irrradiation. Kinetic analysis was employed to evaluate the participation of both types of mechanism under different pH conditions. The rate constant of ~1O_2 total quenching (k_t) by dGMP was determined by steady-state analysis of the ~1O_2 NIR luminescence, whereas the rate constant of the chemical reaction between ~1O_2 and dGMP (k_r) was evaluated from kinetic analysis of concentration profiles obtained by HPLC. The results show that the oxidation of dGMP photosensitized by PT occurs through two competing mechanisms that contribute in different proportions depending on the pH. The dominant mechanism in alkaline media involves the reaction of dGMP with ~1O_2 produced by energy transfer from the PT triplet state to molecular oxygen (type Ⅱ). In contrast, under acidic pH conditions, where PT and the guanine moiety of dGMP are not ionized, the main pathway for dGMP oxidation involves an initial electron transfer between dGMP and the PT triplet state (type Ⅰ mechanism). The biological implications of the results obtained are also discussed.