Modulation of the Directionality of Hole Transfer between the Base and the Sugar-Phosphate Backbone in DNA with the Number of Sulfur Atoms in the Phosphate Group.

This work shows that S atom substitution in phosphate controls the directionality of hole transfer processes between the base and sugar-phosphate backbone in DNA systems. The investigation combines synthesis, electron spin resonance (ESR) studies in supercooled homogeneous solution, pulse radiolysis in aqueous solution at ambient temperature, and density functional theory (DFT) calculations of in-house synthesized model compound dimethylphosphorothioate (DMTP(O)═S) and nucleotide (5'--methoxyphosphorothioyl-2'-deoxyguanosine (G-P(O)═S)). ESR investigations show that DMTP(O)═S reacts with Cl to form the σσ* adduct radical -P-S[Formula: see text]Cl, which subsequently reacts with DMTP(O)═S to produce [-P-S[Formula: see text]S-P-]. -P-S[Formula: see text]Cl in G-P(O)═S undergoes hole transfer to Gua, forming the cation radical (G) via thermally activated hopping. However, pulse radiolysis measurements show that DMTP(O)═S forms the thiyl radical (-P-S) by one-electron oxidation, which did not produce [-P-S[Formula: see text]S-P-]. Gua in G-P(O)═S is oxidized unimolecularly by the -P-S intermediate in the sub-picosecond range. DFT thermochemical calculations explain the differences in ESR and pulse radiolysis results obtained at different temperatures.