Theoretical calculation of pKa using the cluster-continuum model

The pK(a)'s of 17 species from - 10 to 50 were calculated using the ab initio MP2/6-311+G(2df,2p) level of theory and inclusion of solvent effects by the cluster-continuum model, a hybrid approach that combines gas-phase clustering by explicit solvent molecules and solvation of the cluster by the dielectric continuum. In addition, the pure continuum methods SM5.42R and PCM were also used for comparison purposes. Species such as alcohols, carboxylic acids, phenol, acetaldehyde and its hydrate, thiols, hydrochloric acid, amines, and ethane were included. Our results show that the cluster-continuum model yields much better agreement with experiment than do the above-mentioned pure continuum methods, with a rms error of 2.2 pK(a) units as opposed to 7 pK(a) units for the SM5.42R and PCM methods. The good performance of the cluster-continuum model can be attributed to the introduction of strong and specific solute-solvent interactions with the molecules in the first solvation shell of ions. This feature decreases the dielectric continuum contribution to the difference in the solvation free energy between ions, making the method less susceptible to error because of the continuum contribution to solvation. Because the method is not based on extensive parametrizations and it is shown to fare well for several functional groups, the present results suggest that this method could be used as a general approach for predicting reliable pK(a) values.