Abstract
Separation of racemic mixtures is pivotal and remains a challenging task since enantiomers exhibit identical physicochemical properties in achiral environments. Enantioselective membranes gain attention for their potential to achieve efficient and scalable chiral separation, offering a cost-effective and environmentally friendly alternative to traditional methods. Here, we present an innovative enantioselective ion-exchange mixed matrix membrane for the separation of racemic acids, involving quinidine-modified 5 μm silica particles dispersed in poly(ethylene-co-vinyl alcohol) (EVOH) or poly(vinylidene fluoride) (PVDF) matrices. The separation follows a sorption-driven mechanism based on the retarded transport model, requiring periodic regeneration using methanolic ammonium acetate solution. Optimal separation conditions for N-(3,5-dinitrobenzoyl)-leucine enantiomers were found at low ionic strength with a methanol, acetic acid, and ammonium acetate solvent system. Both PVDF-based membranes, prepared via non-solvent-induced phase separation (NIPS) with a high packing ratio of 1.2:1 (particle to polymer), and EVOH-based membranes with 1:1 ratio, prepared via combined vapour-induced phase separation (VIPS) and solvent-evaporation at 50 % relative humidity, achieved ≥98 % enantiomeric excess (ee) after five separation stages. Fluxes averaged on (1513 ± 255) mg/m2/h (PVDF) and (1190 ± 139) mg/m2/h (EVOH) at 1 mg/mL feed concentration with ∼5 % stage-over-stage recoveries. Pressure-driven enantioseparation using PVDF membranes required ∼20 stages to achieve >90 % ee but provided ∼49 % recovery per stage. Leveraging the proven long-lasting performance of chromatographic enantioselective silica, the developed membranes enable scalable semi-continuous separation of acidic racemates. Attractively, this versatile approach is extendable to membranes selective for other chiral compounds.