by Renata Kaczmarek, Samuel Ward, Dipra Debnath,Taisiya Jacobs, Alexander D. Stark, Dariusz Korczyński, Anil Kumar, Michael D. Sevilla, Sergey A. Denisov, Viacheslav Shcherbakov, Pascal Pernot, Mehran Mostafavi, Roman Dembinski, Amitava Adhikary

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.