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

Abstract

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’-O-methoxyphosphorothioyl-2′-deoxyguanosine (G–P­(O–)S)). ESR investigations show that DMTP­(O–)S reacts with Cl2 •– to form the σ2σ*1 adduct radical −P–SCl, which subsequently reacts with DMTP­(O–)S to produce [−P–SS–P−]−. −P–SCl 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–SS–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.

Secondary Electron Attachment-Induced Radiation Damage to Genetic Materials

“… 35 The ESR studies by the Adhikary–Sevilla laboratory and the collaborative work between Adhikary and Mostafavi groups have established that formation of the neutral sugar radical in the backbone via the direct-type effect involves various pathways: (a) ionization–deprotonation, (b) hole transfer from excited base cation radicals to the sugar moiety by deprotonation, (c) phosphate-to-sugar hole transfer, and (d) base-to-sugar hole transfer. 11 , 13 − 16 , 99 − 101 …”

“… ,,− , The carbon-centered radical with the phosphate group attached (C3′•, C5′•) or without (C1′•) are formed in the oxidative pathway of DNA damage involving H-abstraction from the deoxyribose sugar moiety by •OH (indirect effect). ,,,, These same radicals are also formed by ionization–deprotonation and hole transfer from the excited base cation radical to the sugar moiety followed by deprotonation (direct-type effect). ,− C3′•, C4′•, and C5′• subsequently lead to sugar–phosphate bond breaking by β-phosphate elimination. ,,− Adhikary and co-workers have detected the ESR spectral signatures of C5′• (produced via oxidative pathway of radiation damage) and C3′ dephos • (produced by reductive pathway through DEA) in both ion-beam and γ-ray irradiated hydrated DNA (degree of hydration = 12–14 water molecules/nucleotide), where both anion radical and cation radical scavengers were used to isolate the ESR spectrum in irradiated DNA due to only neutral backbone radical (sugar radical) species . The ESR studies by the Adhikary–Sevilla laboratory and the collaborative work between Adhikary and Mostafavi groups have established that formation of the neutral sugar radical in the backbone via the direct-type effect involves various pathways: (a) ionization–deprotonation, (b) hole transfer from excited base cation radicals to the sugar moiety by deprotonation, (c) phosphate-to-sugar hole transfer, and (d) base-to-sugar hole transfer. ,− ,− …”

Low Energy Photoionization of Phosphorothioate DNA-Oligomers and Ensuing Hole Transfer

“…Meanwhile, the close intermolecular distance between PS moieties in the DNA strand allows their rapid combination to form -P-S∴S-P- within ∼20 ns. Based on the above analysis, the transient species absorbing strongly at 410 nm should be assigned to -P-S∴S-P- instead of PS • …”