A Hybrid ASL-MD Strategy To Explain Propylparaben Solvation and Solubility in Binary Acetone/Carbon Tetrachloride Mixtures: Combining Simulation, Theory, and Experiment.

This work presents a comprehensive study integrating experimental measurements, molecular dynamics (MD) simulations, and thermodynamic modeling to elucidate the supramolecular structure and solubility of propylparaben (PPB) in binary acetone-carbon tetrachloride mixtures. Experimentally, PPB solubility exhibits a strong positive deviation from additivity, increasing by over 2 orders of magnitude with acetone concentration. MD simulations of saturated solutions reveal the detailed distribution of PPB self-associates and PPB-acetone heteroassociates. Crucially, the simulations show that the mole and volume fractions of free PPB monomers increase with acetone content, indicating a significant deviation from ideal associated solution behavior. The study introduces a novel hybrid solubility analysis method that directly links MD-derived supramolecular structure with the thermodynamic ASL model, eliminating the need for a priori assumptions about association reactions. This approach quantitatively separates the contributions to solubility changes, revealing that molecular association provides the second-largest positive contribution, with a maximum at an acetone mole fraction of ∼0.05. The dominant factor enhancing solubility, however, is the favorable universal (nonspecific) interaction between components of the solution. The results advance the fundamental understanding of solvation in complex media and provide a framework for the rational selection and optimization of solvent compositions in separation and crystallization processes.