The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship

Abstract

The aqueous solubility of liquids and solids, as log S(W), has been correlated with an amended solvation equation that incorporates a term in Sigma alpha(2)(H) x Sigma beta(2)(H), where the latter are the hydrogen bond acidity and basicity of the solutes, respectively. Application to a training set of 594 compounds led to a correlation equation with a standard deviation, SD, of 0.56 log units. For a test set of 65 compounds, the SD was 0.50 log units, and for a combined correlation equation for 659 compounds, the SD was 0.56 log units. The correlation equations enable the factors that influence aqueous solubility to be revealed. The hydrogen-bond propensity of a compound always leads to an increase in solubility, even though the Sigma alpha(2)(H) x Sigma beta(2)(H) term opposes solubility due to interactions in the liquid or solid. Increase in solute dipolarity/polarizability increases solubility, whereas an increase in solute excess molar refraction, and especially, volume decrease solubility. The solubility of Bronsted acids and bases is discussed, and corrections for the fraction of neutral species in the saturated solution are graphically presented.