Density functional study of protonation of deoxynucleosides: Electrophilic active sites and proton affinities

Possible low-energy tautomers and their interconversions, electrophilic active sites, and proton affinities of deoxyribonucleosides have been studied by the density functional theory. The calculated results indicate that the protonation features of deoxyribonucleosides are less changed as compared with their corresponding bases. Proton affinities of 2′-deoxyriboguanosine (dG), 2′-deoxyribocytidine (dC), 2′-deoxyriboadenosine (dA), and 2′-deoxyribothymidine (dT) at the most favored sites are 240.6 kcal mol^-1 (N7), 238.5 kcal mol^-1 (N3), 233.4 kcal mol ^-1 (N1), and 217.9 kcal mol^-1 (O4), respectively. Predicted tautomerization barriers are substantially high and exclude the coexistence possibility of their low-energy tautomers at room temperatures. Calculations show good agreement with experiments and provide a basis for description of structures and energetics of neutral and protonated deoxyribonucleosides.