Ab initio quantum mechanical calculations of pK(a)s of isolated molecules and molecules undergoing chemical reactions: pK(a) of acetic acid during alpha-proton abstraction

Aqueous-phase proton affinities (PA(aq)) were calculated for 14 carboxylic acids, 15 amines, and 16 alcohols using ab initio quantum mechanically calc ulated gas phase proton affinities (PA(gas), MP2/6-31 + G**//HF/6-31 + G**) and relative solvation energies of the acid and its conjugate base (Delta Delta G(solv), IPCM-HF/6-31 + G**) calculated with the isodensity surface-p olarised continuum model (PA(aq) = PA(gas) + AAG(solv)). After empirical li near scaling the correlation coefficients (r(2)) between the calculated and experimental pK(a)s were 0.94-0.98 for the three groups of molecules. Carb oxylic acids, amines and alcohols have different correlation equations indi cating systematic errors in the calculated energies for molecules with diff erent acidic groups. The linear equation for carboxylic acids was used to e stimate the change in the pK(a) of the carboxyl group of acetic acid from t he calculated 4.8 (pK(a)(exp) = 4.6) of the reactant, acetic acid, to 13.3 of the product, enolate of carboxylic acid, during cc-proton abstraction by methoxide. It was shown that the calculated PA(aq) values can be used to e stimate pK(a)s of isolated molecules and molecules undergoing chemical reac tions.