Prediction of relative pK a values of amines by quantum chemical calculations

Abstract

An approach based on the cluster-continuum model is used to calculate some relative pK a values. For this purpose, one and two explicit water molecules are combined with the polarizable continuum model (PCM), conductor-like polarizable continuum model (CPCM), and integral equation formalism polarizable continuum model (IEF-PCM) to accurately predict solvation free energies. Pure continuum model results are also presented for comparison. B3LYP/6-31+G* level of theory is used for prediction of both gas-phase and solvation free energies during all calculations. Atoms in molecules analyses are also presented to characterize the strength of intermolecular hydrogen bonds between the solvent molecules and the bases. Results are in line with previous studies and show that introducing explicit solvent molecules has a drastic effect on the prediction of acidity constants of amines.