Proton solvation in protic and aprotic solvents

Protonation pattern strongly affects the properties of molecular systems. To determine protonation equilibria, proton solvation free energy, which is a central quantity in solution chemistry, needs to be known. In this study, proton affinities (PAs), electrostatic energies of solvation, and pKA values were computed in protic and aprotic solvents. The proton solvation energy in acetonitrile (MeCN), methanol (MeOH), water, and dimethyl sulfoxide (DMSO) was determined from computed and measured pKA values for a specially selected set of organic compounds. pKA values were computed with high accuracy using a combination of quantum chemical and electrostatic approaches. Quantum chemical density functional theory computations were performed evaluating PA in the gas‐phase. The electrostatic contributions of solvation were computed solving the Poisson equation. The computations yield proton solvation free energies with high accuracy, which are in MeCN, MeOH, water, and DMSO −255.1, −265.9, −266.3, and −266.4 kcal/mol, respectively, where the value for water is close to the consensus value of −265.9 kcal/mol. The pKA values of MeCN, MeOH, and DMSO in water correlates well with the corresponding proton solvation energies in these liquids, indicating that the solvated proton was attached to a single solvent molecule. © 2016 Wiley Periodicals, Inc. Proton affinities, electrostatic energies of salvation, and pKA values of a reference set of organic molecules are computed combining quantum chemical and electrostatic approaches. Proportional to the free energy of proton dissociation, the pKA calculation is strongly dependent on the free energy of proton solvation. Such energy is here determined with high accuracy in order to obtain the best match between measured and computed pKA values in acetonitrile, methanol, water, and dimethyl sulfoxide.