Solubilities and Transfer Free Energies of Hydrophobic Amino Acids in Polyol Solutions: Importance of the Hydrophobicity of Polyols

The purpose of this work was to investigate the difference in the hydrophobicities of various polyols and the nature of interactions between hydrophobic amino acid side chains and polyols. The interactions were explored by conducting solubility studies of three amino acid derivatives, N‐acetyl tryptophanamide (NATA), N‐acetyl leucinamide (NALA), and N‐acetyl glycinamide (NAGA), in the solutions of sorbitol, sucrose, trehalose, glycerol, ethylene glycol, ribose, and deoxyribose. Hydrophobicity index of polyols was calculated using molecular modeling. An increase in the solubility of the hydrophobic side chains of tryptophan and leucine was observed with an increase in the hydrophobicity index of polyols. Transfer free energies of NATA from water to polyols solutions were negative, whereas those for NALA were positive for all polyols except glycol. This study shows that the hydrophobic nature of polyols plays an important role in polyol-side chain interactions. Solubility behavior observed for NATA and NALA in different polyols indicates that polyols can interact differently with the same side chain depending on the nature of the polyol and the side chain. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3096-3104, 2011