Study on the Correlation and Prediction of Octanol/Water Partition Coefficients by Quantum Chemical Calculations

Abstract

The influence and applicability of several quantum chemically obtained descriptors on the correlation/prediction of octanol/water partition coefficients (log Pow) at 298 K is thoroughly studied. The log Pow values are expressed as a linear equation in terms of several contributions to the chemical potential. The chosen parameters reflect the molecular interactions between the solute and the solvent molecules and account for cavity effects, polarity and polarizability, and the distribution of the electrostatic potential. The description of hydrogen-bonding by the sums of minima and maxima of the electrostatic potential is studied in detail for a wide variety of molecules. All descriptors can be easily computed by standard ab initio methods and result in good correlations with experimental log Pow values. The prediction power of the method is tested for a set of solutes, possessing multiple functional groups, intramolecular hydrogen-bonding, and zwitterionic structures.