Petroselli Gabriela, Dántola M Laura, Cabrerizo Franco M, Capparelli Alberto L, Lorente Carolina, Oliveros Esther, Thomas Andrés H
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CONICET, Casilla de Correo 16, Sucursal 4, (1900) La Plata, Argentina.
J Am Chem Soc. 2008 Mar 12;130(10):3001-11. doi: 10.1021/ja075367j. Epub 2008 Feb 16.
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 ((1)O2) (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 (1)O2 total quenching (k(t)) by dGMP was determined by steady-state analysis of the (1)O2 NIR luminescence, whereas the rate constant of the chemical reaction between (1)O2 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 (1)O2 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.
紫外线A辐射（320 - 400纳米）通过不同的光敏反应诱导DNA分子及其组分发生损伤。在这些过程中，光敏氧化反应可能通过电子转移或氢原子提取（I型）和/或单线态分子氧（(1)O2）的产生（II型）而发生。蝶呤是广泛存在于生物系统中的杂环化合物，参与相关生物过程并能够作为光敏剂。我们研究了在紫外线A照射下，蝶呤（PT）在水溶液中对5'-单磷酸-2'-脱氧鸟苷（dGMP）的光敏氧化作用。采用动力学分析来评估在不同pH条件下两种机制的参与情况。通过对(1)O2近红外发光的稳态分析测定dGMP对(1)O2的总猝灭速率常数（k(t)），而通过高效液相色谱法获得的浓度分布的动力学分析评估(1)O2与dGMP之间化学反应的速率常数（k(r)）。结果表明，PT光敏化的dGMP氧化通过两种相互竞争的机制发生，这两种机制根据pH的不同以不同比例起作用。碱性介质中的主要机制涉及dGMP与由PT三重态向分子氧的能量转移产生的(1)O2的反应（II型）。相反，在酸性pH条件下，PT和dGMP的鸟嘌呤部分未电离，dGMP氧化的主要途径涉及dGMP与PT三重态之间的初始电子转移（I型机制）。还讨论了所得结果的生物学意义。
