Unveiling the Molecular Driving Forces of Pollutant Extraction by Hydrophobic Eutectic Solvents

Abstract Hydrophobic eutectic solvents (HES) are emerging as sustainable alternatives to conventional organic solvents for the extraction of molecular pollutants from water. Yet, their selectivity remains poorly understood, hindering the predictive design of eutectic solvents beyond empirical success. Here, we present a multiscale strategy to rationalize and predict solute partitioning in HES. Focusing on bisphenol A (BPA) in trioctylphosphine oxide (TOPO):menthol as a prototypical system, we combine monophasic and biphasic molecular dynamics with quantum energy decomposition of dominant solvation motifs. Our methodology captures the experimentally measured spontaneous migration of BPA and its thermodynamic stabilization in the HES phase, and it identifies the microscopic origin of selectivity: cooperative hydrogen bonding couples with strong dispersion and polarization in the hydrophobic eutectic microenvironment. The extension of the workflow to a second experimentally relevant HES provides additional evidence supporting the transferability of the mechanistic interpretation and illustrates its potential as a computational framework for the rational screening and design of HES formulations.