Naumov, S. and von Sonntag, C. The Energetics of Rearrangement and Water Elimination Reactions in the Radiolysis of the DNA Bases in Aqueous Solution (eaq− and ·OH Attack): DFT Calculations. Radiat. Res. 169, 355–363 (2008).
DFT calculations on the relative stability of various nucleobase radicals induced by eaq− and ·OH have been carried out for assessing the energetics of rearrangements and water elimination reactions, taking the solvent effect of water into account. Uracil and thymine radical anions are protonated fast at O2 and O4, whereby the O2-protonated anions are higher in energy (50 kJ mol−1, equivalent to a 9-unit lower pKa). The experimentally observed pKa = 7 is thus that of the O4-protonated species. Thermodynamically favored protonation occurs slowly at C6 (driving force, thymine: 49 kJ mol−1, uracil: 29 kJ mol−1). The cytosine radical anion is rapidly protonated by water at N3. Final protonation at C6 is disfavored here. The kinetically favored pyrimidine C5 ·OH adducts rearrange into the thermodynamically favored C6 ·OH adducts (driving force, thymine: 42 kJ mol−1). Very similar in energy is a water elimination that leads to the Ura-5-methyl radical. Purine ·OH adducts at C4 and C5 (plus C2 in guanine) eliminate water in exothermic reactions, while water elimination from the C8 ·OH adducts is endothermic. The latter open the ring en route to the FAPY products, an H transfer from the C8·OH to N9 being the most likely process.