One Way Traffic: Base-to-backbone Hole Transfer in Nucleoside Phosphorodithioates.

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 mu s 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 sigma(2)-sigma*(1)-bonded dimer anion radical [-P-2S-. 2S-P-](-) [Delta G (150 K, DFT)=-7.2 kcal mol(-1)]. However, [-P-2S-. 2S-P-](-) formation was not observed by pulse radiolysis [Delta G degrees (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.