The effect of hydrogen bonding on protonation energies and ion pair formation Original Research Article

The effects of environmental hydrogen bonding by solvent molecules on the stability of charged groups and ion pairs have been analyzed by ab initio calculations on molecular models representing acidic and basic amino acid residues. By constructing closed reactions cycles, the energetics of the isolated and solvated groups can be directly compared and the origin of the changes in relative stability exhibited. The results of the calculations showed that the solvent molecules stabilize interacting pairs in both the neutral and charged states, but that the effects shift the equilibrium towards the latter. The analysis further indicated that the main contribution to this effect is due to the changes in the work required to form the charges attendant upon solvation. Moreover, although the relative stability of the neutral and charged states is primarily controlled by electrostatic effects, it can be modulated by additional short range interactions when the species are close to each other. In such cases the relative stability of the states predicted by the total interaction energy may be different to what is obtain from just the electrostatic interactions.