Enthalpies of hydration of N-methylacetamide by one, two, and three waters and the effect upon the C=O stretching frequency. An ab initio DFT study

DFT calculations at the B3LYP/D95++(d, p) level of clusters of N-methylacetamide (NMA) with one, two, and three waters that were geometrically optimized on the counterpoise-corrected potential energy surfaces show that the gas-phase enthalpy of the interactions of NMA with three waters is -14.11 kcal/mol. Since the interactions between the three waters is 0.99 kcal/mol, the interaction enthalpy would become -15.10 if these interactions were subtracted. The internal geometry of the NMA molecule is sensitive to the degree of hydration, as are the H-bond lengths. Changes in the internal bond lengths with degree of hydration are approximately additive. The calculated C=O stretching frequencies correlate extremely well with the calculated C=O bond lengths, which suggests that the solvent effect upon this stretch could not be a purely electrostatic interaction. The calculated C=O stretch for NMA solvated by three waters in the gas phase agrees very well with that experimentally observed in aqueous solution.