Acidity of Organic Molecules in the Gas Phase and in Aqueous Solvent

Abstract

Using a combination of ab initio, DFT and continuum solvation methods, the gas phase and aqueous acidities for a set of weak organic acids with high pKa values, which cannot be measured experimentally in aqueous solvent, have been calculated. Comparison of the computed and experimental data for different terms used in the thermodynamic cycle for the calculation of pKa values allowed us to estimate that the errors in the pKa calculations are of order of 2 pKa units, i.e., less than 10% of the expected pKa values for the studied weak organic acids. It is shown that inclusion of explicit water molecules in the solute cavity of compounds with pKa values over 40 could lead to dubious results due to the inappropriate description of the corresponding anion solvation. Acidity trends for compounds in the gas phase and in aqueous solvent were found to be different, due to the effects of aqueous solvation.