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

The aqueous solubility of liquids and solids, as log S-W, has been correlat ed with an amended solvation equation that incorporates a term in Sigma alp ha(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 o f 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 un its, 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 compo und 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 so lubility, whereas an increase in solute excess molar refraction, and especi ally, volume decrease solubility. The solubility of Bronsted acids and base s is discussed, and corrections for the fraction of neutral species in the saturated solution are graphically presented.