Calculation of Aqueous Solubility of Organic Compounds from Molecular Structural Properties

Abstract

The quantitative structure-activity relationships (QSAR) correlations were developed for the aqueous solubility of organic compounds at 298.15, 473.15, and 573.15 K. To elucidate the molecular structural variables to control the solvation phenomena, we firstly developed the QSAR correlation of solubility of 108 organic molecules in water at 298.15 K with the use of experimentally and theoretically derivable variables. The experimental variable used was the octanol-water partition coefficient and melting point, while the theoretical variables were LUMO energy and total molecular surface area, which were determined with the COSMO-PM3 method. Based on the results at 298.15 K, the QSAR correlations for aqueous solubility at 473.15 K and 573.15 K were determined with the use of the literature solubility data for 21 compounds at these two high temperatures. It was found that the QSAR correlation with COSMO-PM3 method is able to predict the aqueous solubility of organic compounds at 473.15 and 573.15 K from the molecular structural properties and the melting temperature, since the octanol-water partition coefficient can be predicted from atom/fragment contribution method.