Results from DFT calculations indicate that states originating from gas-phase ionization of the phosphate and the base are degenerate in syn-5'-dGMP- and that bulk hydration lowers the base-localized ionization energy by <0.5 eV. Local ionization maps show that micro-hydration leads to the formation of donor and acceptor hydrogen bonds and the ionization energy decreases or increases in each case respectively. The S(N)2 transition states of the methylation reactions of guanine with methane diazonium ions are lower at the N7 than at the O-6 sites and they are influenced by local ionization energy and steric interference. (C) 2017 Elsevier B.V. All rights reserved.