Investigation of Microscopic Hydration of Protonated Cytosine by Density Functional Theory Calculations

Abstract

Depending on the protonation site, protonated cytosine, i.e., CH+, is known to gain different degrees of stabilization from hydration. To deepen our understanding of the solvation of protonated cytosine at the molecular level, hydrated clusters of protonated cytosine, CH+(H2O)(n) = 1-6, as a microscopic hydration model, were investigated. Using the hydrated clusters, the stepwise solvation of protonated cytosine molecules protonated at two different sites, N3 and O2, was studied using density functional theory (DFT) calculations (B3LYP/6-311+G(d,p)). N3-protonated cytosine, CNH+, was found to have a stronger interaction with water than O2-protonated cytosine, COH+, by 1 kcal/mol per water solvent. For CNH+, the hydration of four water molecules by hydrogen bonding was shown to account for approximately 75% of the bulk solvation energy, and further hydration with six waters accounts for the majority of the bulk stabilization. However, unlike the case of CNH+, the binding of water to the pyrimidine ring side of COH+ was observed to be fairly repulsive. In addition, the initial stepwise hydration energies for COH+, which were mostly governed by hydrogen bonding, were weaker than those predicted for CNH+. These results suggest that the higher charge density carried by CNH+ favors both hydrogen bonding and ion-dipole interactions, thus resulting in the greater stabilization of CNH+ than COH+ in an aqueous environment.