Enhancement of biomolecules solubility in aqueous media using designer solvents as additives: An experimental and COSMO-based models' approach

The knowledge about the solubility behavior of different biomolecules can be of interest to the pharmaceutical, chemical, and food industries. In this work, the designer solvents were evaluated as additives to aqueous media to enhance the solubility of hydrophobic biomolecules, namely: quercetin, curcumin, and gallic acid. The solubilities of these biomolecules were explored in terms of experimental data and COSMO-based models' prediction (COSMO-RS and COSMO-SAC). The following designer solvents were evaluated as additives: DES (composed of cholinium chloride and xylitol, 2:1 M fraction), cholinium chloride (HBA), xylitol (HBD) and the simple mixture of cholinium chloride and xylitol in the same molar ratio of the DES. For the more hydrophobic biomolecules, i.e., curcumin, and quercetin, these solvents promoted an increase of solubility. The quercetin solubility increased more than 1000-fold in the solution containing 70 wt% of cholinium chloride compared to the pure water. In the same conditions, the curcumin solubility increased around 700-fold. For the less hydrophobic biomolecule, gallic acid, a hydrotrope effect was observed when DES and the simple mixture of cholinium chloride and xylitol were used as an additive. Moreover, comparing the aqueous solutions containing DES with that one composed of the cholinium chloride and xylitol mixture is possible to observe the effect of the hydrogen bonds from DES at low water content solutions. Also, the COSMO models were able to predict the affinity behavior of biomolecules in different solvents, and the COSMO-SAC predicted the hydrotrope behavior of the aqueous solution of cholinium chloride when solubilizing gallic acid.