Experimental and Theoretical Study of Deprotonation of DNA Adenine Cation Radical

Among all the DNA components, extremely redox-active guanine (G) and adenine (A) bases are subject to facile loss of an electron and form cation radicals (G +· and A +· ) when exposed to irradiation or radical oxidants. The subsequent deprotonation of G +· and A +· can invoke DNA damage or interrupt hole transfer in DNA. However, compared with intensive reports for G +· , studies on the deprotonation of A +· are still limited at present. Herein, we investigate the deprotonation behavior of A +· by time-resolved laser flash photolysis. The deprotonation product of A(N 6 -H) · is observed and the deprotonation rate constant, (2.0±0.1)×10 7 s -1 , is obtained at room temperature. Further, the deprotonation rate constants of A +· are measured at temperatures varying from 280 K to 300 K, from which the activation energy for the N 6 -H deprotonation is determined to be (17.1±1.0) kJ/mol by Arrhenius equation. In addition, by incorporating the aqueous solvent effect, we perform density functional theory calculations for A +· deprotonation in free base and in duplex DNA. Together with experimental results, the deprotonation mechanisms of A +· in free base and in duplex DNA are revealed, which are of fundamental importance for understanding the oxidative DNA damage and designing DNA-based electrochemical devices.