Sugar Radical Formation by a Proton Coupled Hole Transfer in 2′-Deoxyguanosine Radical Cation (2′-dG^•+): A Theoretical Treatment

Abstract

Previous experimental and theoretical work has established that electronic excitation of a guanine cation radical in nucleosides or in DNA itself leads to sugar radical formation by deprotonation from the dexoxyribose sugar. In this work we investigate a ground electronic state pathway for such sugar radical formation in a hydrated one electron oxidized 2′-deoxyguanosine (dG•+ + 7H2O), using density functional theory (DFT) with the B3LYP functional and the 6-31G* basis set. We follow the stretching of the C5′-H bond in dG•+ to gain an understanding of the energy requirements to transfer the hole from the base to sugar ring and then to deprotonate to proton acceptor sites in solution and on the guanine ring. The geometries of reactant (dG•+ + 7H2O), transition state (TS) for deprotonation of C5′ site and product (dG(•C5′, N7-H+) + 7 H2O) were fully optimized. The zero point energy (ZPE) corrected activation energy (TS) for the proton transfer (PT) from C5′ is calculated to be 9.0 kcal/mol and is achieved by stretching the C5′-H bond by 0.13 Å from its equilibrium bond distance (1.099 Å). Remarkably, this small bond stretch is sufficient to transfer the “hole” (positive charge and spin) from guanine to the C5′ site on the deoxyribose group. Beyond the TS, the proton (H+) spontaneously adds to water to form a hydronium ion (H3O+) as an intermediate. The proton subsequently transfers to the N7 site of the guanine (product). The 9 kcal/mol barrier suggests slow thermal conversion of the cation radical to the sugar radical but also suggests that localized vibrational excitations would be sufficient to induce rapid sugar radical formation in DNA base cation radicals.

Proton-Coupled Electron Transfer in DNA on Formation of Radiation-Produced Ion Radicals

“…The hole transfer from base to sugar is, of course, accompanied by an electron transfer from the sugar to the one electron oxidized base. Thus the overall sugar radical formation process is clearly a proton coupled hole transfer (PCHT) (or proton coupled electron transfer (PCET)) as depicted in Scheme 4 228…”

Electron-Induced Repair of 2′-Deoxyribose Sugar Radicals in DNA: A Density Functional Theory (DFT) Study

“…Using EPR (electron paramagnetic resonance)/ENDOR (electron nuclear double resonance), sugar radicals at each of the carbon sites has been shown to result from direct radiation of nucleosides and nucleotides in the solid state [ 25 , 26 ]. The experimental formation of the C5′ • sugar radical from 2′-deoxyguanosine radical cation (2′-dG •+ ) was proposed to occur via a proton-coupled hole transfer (PCHT) mechanism from the base to the sugar site which was supported by the DFT [ 27 ].…”

One-Electron Oxidation of Neutral Sugar Radicals of 2′-Deoxyguanosine and 2′-Deoxythymidine: A Density Functional Theory (DFT) Study

“…17–19,23 C 5′ • sugar radical formation from one-electron oxidized 2′-deoxyguanosine (2′-dG •+ ) by proton coupled hole transfer (PCHT) was proposed using theoretical calculations. 24 Using EPR/ENDOR sugar radicals at each of the carbon sites have been shown to result from direct radiation damage of nucleosides and nucleotides in the solid state. 25, 26 …”