Department of Chemistry, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, 21218, USA.
Department of Chemistry, Beijing Normal University, Beijing, 100875, P. R. China.
Angew Chem Int Ed Engl. 2020 Aug 3;59(32):13406-13413. doi: 10.1002/anie.202005300. Epub 2020 Jun 2.
Guanine radicals are important reactive intermediates in DNA damage. Hydroxyl radical (HO ) has long been believed to react with 2'-deoxyguanosine (dG) generating 2'-deoxyguanosin-N1-yl radical (dG(N1-H) ) via addition to the nucleobase π-system and subsequent dehydration. This basic tenet was challenged by an alternative mechanism, in which the major reaction of HO with dG was proposed to involve hydrogen atom abstraction from the N2-amine. The 2'-deoxyguanosin-N2-yl radical (dG(N2-H) ) formed was proposed to rapidly tautomerize to dG(N1-H) . We report the first independent generation of dG(N2-H) in high yield via photolysis of 1. dG(N2-H) is directly observed upon nanosecond laser flash photolysis (LFP) of 1. The absorption spectrum of dG(N2-H) is corroborated by DFT studies, and anti- and syn-dG(N2-H) are resolved for the first time. The LFP experiments showed no evidence for tautomerization of dG(N2-H) to dG(N1-H) within hundreds of microseconds. This observation suggests that the generation of dG(N1-H) via dG(N2-H) following hydrogen atom abstraction from dG is unlikely to be a major pathway when HO reacts with dG.
鸟嘌呤自由基是 DNA 损伤中的重要反应中间体。羟基自由基（HO ）长期以来被认为通过加成到核碱基π系统并随后脱水与 2'-脱氧鸟嘌呤（dG）反应生成 2'-脱氧鸟苷-N1-基自由基（dG（N1-H））。这一基本原理受到了另一种机制的挑战，其中 HO 与 dG 的主要反应被提议涉及从 N2-氨基中提取氢原子。形成的 2'-脱氧鸟苷-N2-基自由基（dG（N2-H））被提议迅速互变异构为 dG（N1-H）。我们首次通过 1 的光解以高产率独立生成 dG（N2-H）。在纳秒激光闪光光解（LFP）下直接观察到 1 的 dG（N2-H）的形成。通过 DFT 研究证实了 dG（N2-H）的吸收光谱，并首次解析了反式和顺式 dG（N2-H）。LFP 实验在数百微秒内没有证据表明 dG（N2-H）向 dG（N1-H）的互变异构。这一观察结果表明，当 HO 与 dG 反应时，通过 dG 从 dG 中提取氢原子生成 dG（N1-H）不太可能是主要途径。
