One Way Traffic: Base-to-Backbone Hole Transfer in Nucleoside Phosphorodithioate

The directionality of the hole-transfer processes between DNA backbone and base was investigated by using phosphorodithioate [P(S^- )=S] components. ESR spectroscopy in homogeneous frozen aqueous solutions and pulse radiolysis in aqueous solution at ambient temperature confirmed initial formation of G^.+ -P(S^- )=S. The ionization potential of G-P(S^- )=S was calculated to be slightly lower than that of guanine in 5'-dGMP. Subsequent thermally activated hole transfer from G^.+ to P(S^- )=S led to dithiyl radical (P-2S^. ) formation on the μs timescale. In parallel, ESR spectroscopy, pulse radiolysis, and density functional theory (DFT) calculations confirmed P-2S^. formation in an abasic phosphorodithioate model compound. ESR investigations at low temperatures and higher G-P(S^- )=S concentrations showed a bimolecular conversion of P-2S^. to the σ² -σ*¹ -bonded dimer anion radical [-P-2S $$ 2S-P-]^- [ΔG (150 K, DFT)=-7.2 kcal mol^-1 ]. However, [-P-2S $$ 2S-P-]^- formation was not observed by pulse radiolysis [ΔG° (298 K, DFT)=-1.4 kcal mol^-1 ]. Neither P-2S^. nor [-P-2S $$ 2S-P-]^- oxidized guanine base; only base-to-backbone hole transfer occurs in phosphorodithioate.