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Independent Generation and Reactivity of 2′-Deoxyguanosin‑N1‑yl Radical

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journal contribution
posted on 11.06.2020, 14:37 by Liwei Zheng, Marc M. Greenberg
2′-Deoxyguanosin-N1-yl radical (dG­(N1-H)) is the thermodynamically favored one-electron oxidation product of 2′-deoxyguanosine (dG), the most readily oxidized native nucleoside. dG­(N1-H) is produced by the formal dehydration of a hydroxyl radical adduct of dG as well as by deprotonation of the corresponding radical cation. dG­(N1-H) were formed as a result of the indirect and direct effects of ionizing radiation, among other DNA damaging agents. dG­(N1-H) was generated photochemically (λmax = 350 nm) from an N-aryloxy-naphthalimide precursor (3). The quantum yield for photochemical conversion of 3 is ∼0.03 and decreases significantly in the presence O2, suggesting that bond scission occurs from a triplet excited state. dG is formed quantitatively in the presence of excess β-mercaptoethanol. In the absence of a reducing agent, dG­(N1-H) oxidizes 3, decreasing the dG yield to ∼50%. Addition of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) as a sacrificial reductant results in a quantitative yield of dG and two-electron oxidation products of 8-oxodGuo. N-Aryloxy-naphthalimide 3 is an efficient and high-yielding photochemical precursor of dG­(N1-H) that will facilitate mechanistic studies on the reactivity of this important reactive intermediate involved in DNA damage.