Surfactant-Mediated Enantioselective Extraction: Interfacial Behavior Investigation from a Microscopic Perspective

Abstract Enantioselective liquid–liquid extraction (ELLE) based on cyclodextrin host–guest recognition is a promising green strategy for chiral resolution. However, its industrial application is often hindered by restricted chiral recognition efficiency and ill-defined interfacial mass transfer mechanisms. In this work, a multiscale approach─integrating macro-equilibrium experiments, molecular dynamics simulations, and quantum chemical calculations─was employed to decode the interfacial molecular interactions and their decisive roles in the ELLE of ibuprofen. The interface was regulated and reconstructed through the introduction of surfactants. The anionic surfactant SDS shortened extraction equilibrium time by approximately 30%, while the facial amphiphilic NaDC extended equilibration but improved the enantiomeric excess. MD simulations revealed that the addition of SDS and NaDC increased the interfacial thickness from 0.41 nm by 1.23 and 1.51 times, respectively. Via umbrella sampling, the chiral migration process exhibited characteristic free-energy changes of approximately −11.48 kJ·mol–1 and +35.58 kJ·mol–1 when transferring from the organic and aqueous phases to the interface, respectively. Furthermore, quantum chemical analysis quantified the interaction energy differences, demonstrating that steric hindrance and hydrogen-bonding intensity variations drove the observed changes in equilibrium parameters. These findings establish a conceptual microscopic model for interface-mediated chiral partitioning, providing a robust theoretical framework for optimizing separation efficiency and process intensification in ELLE systems.