Acid Dissociation Equilibrium and Singlet Molecular Oxygen Quantum Yield of Acetylated 6,8–Dithioguanosine in Aqueous Buffer Solution

Abstract

2’,3’,5’–Tri–O–acetyl–6,8–dithioguanosine (taDTGuo) is a modified nucleoside of drug 6–thioguanine and further developed as a potential photochemotherapeutic agent due to its desirable properties of photosensitivity to UVA light and singlet molecular oxygen generation. The photochemical characteristics of taDTGuo under biological conditions (namely in aqueous solution) were intensively investigated by the steady–state absorption and emission, time–resolved near–infrared emission measurements, and quantum chemical calculations. taDTGuo was found to be held in sequential acid dissociation equilibria within pH 3.79–11.93. With the global fitting analysis of the absorption spectra at various pHs, two pKa values of the equilibria were determined to be 7.02 ± 0.01 and 9.79 ± 0.01. Quantum chemical calculations suggested that its mono– and di–anionic species in the ground state should be 1–imide anionic form (N1–taDTGuo–) and 1,7–di–imide anionic form (taDTGuo2–) respectively. taDTGuo generates singlet molecular oxygen effectively and has pH–dependent quantum yields. In conclusion, taDTGuo would be most useful as a potent agent for photochemotherapy under certain carcinomatous pH conditions