Towards first principles prediction of pKa: COSMO-RS and the cluster-continuum approach

Frank Eckert (1) , Michael Diedenhofen (1) , Andreas Klamt (1, 2)

1 COSMOlogic GmbH & Co KG
2 Institute of Physical and Theoretical Chemistry

The COSMO-RS method, a post quantum chemistry extension of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulation, has been applied to the prediction of aqueous pKa of acids and bases. The combination of the COSMO-RS approach to pKa prediction with the cluster-continuum approach (explicit solvation of the solute compound with one ore more solvent molecules) was used on three data sets consisting of 94 acids and 75 bases. Correlation of the calculated free energies of dissociation in water with the experimental aqueous pKa of the solute acids and bases in their bare state and explicitly solvated by one or two solvent molecules showed an increase of the regression slope with the number of explicit solvent molecules thus showing a regression slope that is closer to the theoretical value than the slope found for bare solutes. It was found that the cluster-continuum approach is limited to a pKa range of strong to moderately weak acids and bases, because the optimizations of the solvent-solute complexes of the ionic species of very weak acids (such as the anion of tert-butanol) did not lead to the desired complexes but yielded dissociation products.

Mots clés: Physical Sciences

Frank Eckert, Michael Diedenhofen, Andreas Klamt. Towards first principles prediction of pKa: COSMO-RS and the cluster-continuum approach. Molecular Physics, 2010, 108 (03-04), pp.229-241. ⟨10.1080/00268970903313667⟩. ⟨hal-00580701⟩