THEORETICAL-STUDIES ON HYDRATION OF PYRROLE, IMIDAZOLE, AND PROTONATED IMIDAZOLE IN THE GAS-PHASE AND AQUEOUS-SOLUTION

Ab initio calculations using HF/6-31G* and MP2/6-31G* total geometry optimization were carried out in the gas phase for water, pyrrole, imidazole, and protonated imidazole monomers and various monohydrates of each organic. Optimized geometries for the ring systems are in good agreement with the experimental structures; normal frequencies are systematically overestimated. Using MP2/6-311++G** single point calculations, the gas-phase protonation free energy of imidazole was within 2.3 kcal/mol of the experimental value. Free energy calculations for the water-ring system complexes allowed us to estimate the relative populations of the monohydrates with different geometries. The in-plane hydration of pyrrole is preferred by 1.8 kcal/mol over the out-of-plane hydrated form. Imidazole is preferentially hydrated by 1.7 kcal/mol at NI rather than at N3. The statistical perturbation method was used in Monte Carlo simulations to predict relative solvation energy terms. The relative solvation free energy of imidazole referred to pyrrole is -4.1 kcal/mol, and the relative solvation enthalpy is -10 to -12 kcal/mol. The hydrogen bond geometric parameters in solution are reasonably different from those in gas-phase monohydrates optimized using the OPLS interaction potential. The geometric parameters and relative energies for the monohydrates are closer to values obtained in the MP2 rather than HF ab initio calculations. The only remarkable difference between OPLS and MP2 results were found for the imidazole hydration at its N3 site. In dilute aqueous solution the pyrrole molecule forms a hydrogen bond of N-H...Ow type in the molecular plane. The neutral imidazole forms one in-plane N1-H...Ow hydrogen bond and one less localized hydrogen bond at the N3 site. There are also some water molecules located in the pi-region which form weaker bonds to the solute. The protonated imidazole forms two strong in-plane hydrogen bonds of N-H...Ow type in aqueous solution with several water molecules in the pi-region.