Dissecting Molecular Interactions in Aqueous Deep Eutectic Solvents: A Multi-Scale Study of Choline- and Acetylcholine-Based Propylene Glycol Isomers

Deep eutectic solvents (DESs) based on choline or acetylcholine chlorides with 1,2- or 1,3-propanediol represent promising green alternatives to conventional solvents, yet their thermodynamic behavior is governed by a complex interplay of intermolecular forces. To clarify how water modulates their molecular organization and thermodynamic behavior, this study combines experimental, theoretical, and computational approaches. High-precision density and sound velocity are presented for four DESs─composed of choline chloride (ChCl) or acetylcholine chloride (AChCl) with 1,2-propanediol (1,2-PG) or 1,3-propanediol (1,3-PG)─mixed with water across the entire composition range from 293.15 to 313.15 K. From these data, excess molar volumes and excess isentropic compressibilities were obtained and correlated using Redlich-Kister equations. In addition, Prigogine-Flory-Patterson (PFP) analysis revealed that negative excess functions originate predominantly from strong hydrogen-bond interactions, whose magnitude follows the order AChCl:1,2-PG < ChCl:1,2-PG < AChCl:1,3-PG < ChCl:1,3-PG. Consequently, the interactional contribution, rather than free volume effects, dominates excess molar volume. At the molecular level, a COSMO-RS-based speciation model was developed, quantifying the shifting equilibrium of homo- and heteromolecular pairs and directly linking the stronger self-association of 1,3-PG and AChCl to their attenuated volumetric contraction upon mixing with water. Furthermore, a robust linear regression model was constructed using COSMO-RS molecular descriptors, enabling the accurate prediction of aqueous DES density and revealing the dominant role of glycol self-association and hydration energetics. Together, these results provide a consistent multiscale picture from macroscopic properties to molecular distributions, offering a predictive pathway for the rational design of aqueous DES systems.