Predicting Solubility Limits of Organic Solutes for a Wide Range of Solvents and Temperatures

The solubility of organic molecules is crucial in organic synthesis and industrial chemistry; it is important in the design of many phase separation and purification units, and it controls the migration of many species into the environment. To decide which solvents and temperatures can be used in the design of new processes, trial and error is often used, as the choice is restricted by unknown solid solubility limits. Here, we present a fast and convenient computational method for estimating the solubility of solid neutral organic molecules in water and many organic solvents for a broad range of temperatures. The model is developed by combining fundamental thermodynamic equations with machine learning models for solvation free energy, solvation enthalpy, Abraham solute parameters, and aqueous solid solubility at 298 K. We provide free open-source and online tools for the prediction of solid solubility limits and a curated data collection (SolProp) that includes more than 5000 experimental solid solubility values for validation of the model. The model predictions are accurate for aqueous systems and for a huge range of organic solvents up to 550 K or higher. Methods to further improve solid solubility predictions by providing experimental data on the solute of interest in another solvent, or on the solute's sublimation enthalpy, are also presented.

Automated summary

The solubility of organic molecules is crucial in organic synthesis and industrial chemistry. This study presents a computational method for estimating the solubility of solid neutral organic molecules in water and organic solvents at a wide range of temperatures. The model combines thermodynamic equations with machine learning models for accurate predictions.