Solvmate – a hybrid physical/ML approach to solvent recommendation leveraging a rank-based problem framework†

Abstract

The solubility in a given organic solvent is a key parameter in the synthesis, analysis and chemical processing of an active pharmaceutical ingredient. In this work, we introduce a new tool for organic solvent recommendation that ranks possible solvent choices requiring only the SMILES representation of the solvents and solute involved. We report on three additional innovations: first, a differential/relative approach to solubility prediction is employed, in which solubility is modeled using pairs of measurements with the same solute but different solvents. We show that a relative framing of solubility as ranking solvents improves over a corresponding absolute solubility model across a diverse set of selected features. Second, a novel semiempirical featurization based on extended tight-binding (xtb) is applied to both the solvent and the solute, thereby providing physically meaningful representations of the problem at hand. Third, we provide an open-source implementation of this practical and convenient tool for organic solvent recommendation. Taken together, this work could be of benefit to those working in diverse areas, such as chemical engineering, material science, or synthesis planning.