Effects of microsolvation and aqueous solvation on the tautomers of histidine: a computational study on energy, structure and IR spectrum

Microsolvation and combined microsolvation-continuum approaches are employed to investigate the structures and energies of canonical and zwitterionic histidine conformers. The effect of hydration on the relative conformational stability is examined. The strategy of exploring singly and doubly hydrated structures and the possible microsolvation patterns are described. We find that bonding water molecule may significantly change the relative conformational stabilities. In gas phase, the singly and doubly hydrated canonical forms are more stable than their zwitterionic counterparts. In solution, the continuum solvent model shows that bare zwitterionic form is more stable than bare canonical form by 1.1 kcal/mol. This energy separation is increased to 2.2 and 3.4 kcal/mol with inclusion of one and two explicit water molecules, respectively. We have also observed that the doubly hydrated structures obtained by combining two water molecules simultaneously to the solute molecule are preferred over the stepwise hydration. Hydrogen bond energies for the most stable hydrated histidine tautomers are determined by the atoms in molecules theory. The infrared (IR) spectra for the most stable singly and doubly hydrated structures of both histidine tautomers in gas phase are characterized. The stretching frequencies for NH of imidazole ring and OH of COOH are red shifted due to the hydrations. The IR spectra for the most stable zwitterionic tautomers in solution are also presented and discussed in connection with the comparison to the experiments. The pKa values obtained for the ring protonated zwitterions with two explicit water molecules appear to be in good agreement with the experiments.