High-performance enantioselective ion-exchange mixed matrix membranes based on PVDF and EVOH polymers with cinchona-derived chiral silica particles

Many biologically active substances, such as pharmaceuticals or pesticides, often exist in two forms – mirror images (enantiomers). Although these molecules differ only in their orientation in space, their behavior in the body can be fundamentally different. One form can be effective, the other can be harmful. The separation of racemates, i.e., equimolar mixtures of enantiomers, is therefore crucial, but simultaneously very challenging, because these compounds have identical physicochemical properties in the non-chiral environment.

Enantioselective membranes, which have been the focus of the Research group of Membrane Separations for a long time, represent a promising direction for achieving efficient, scalable, and environmentally friendly chiral separation. As part of a newly published research in the Journal of Membrane Science, a team from ICPF, in collaboration with colleagues from the European Membrane Institute in Montpellier (IEM Montpellier) and the group of Prof. Michal Kohout from the Institute of Organic Chemistry of the University of Chemistry and Technology in Prague, has developed new enantioselective ion exchange membranes with a mixed matrix. The membranes consist of silica gel particles with a size of 5 μm modified with quinidine (chiral selector), embedded in polymer matrices made of polyvinylidene fluoride (PVDF) or polyethylene-co-vinyl alcohol (EVOH). The membranes were prepared using non-solvent-induced phase separation (NIPS) or water vapor (VIPS) phase inversion methods. Among other things, the team investigated the effect of relative humidity and the amount of silica gel particles on membrane formation. Under optimal preparation conditions, it was possible to achieve up to 55% filling of the membrane with particles (see photo below).

Left – PVDF membrane prepared by the phase inversion method with a non-solvent without particles
Right – PVDF membrane prepared using the same technique with 55% particle filling

Separation using the prepared membranes proceeds by a sorption-driven mechanism, in which the transport of one of the enantiomers through the membrane is slowed down due to its preferential interactions with the chiral selector. This was achieved in a concentration-driven or pressure-driven process. Because the chiral binding sites in the membrane are saturated during the separation, the membranes are periodically regenerated by a methanolic solution of ammonium acetate, which displaces the adsorbed enantiomers from the membrane. After five separation steps in the concentration-driven process, the separation of N-3,5-dinitrobenzoyl leucine (model analyte) achieved enantiomeric purity of over 98% and productivity of up to (1513 ± 255) mg/m²/h at an input concentration of 1 mg/ml and an average yield of about 5% per degree. The pressure-driven process required 20 separation stages with a much higher yield of about 49% to achieve an enantiomeric excess of over 90%.

An indisputable advantage of these membranes is easy and quick preparation, allowing scaling to larger scales together with the advantageous geometry of the membranes. The chiral silica gel behaves like a chiral anion exchange and is therefore suitable for separating a wide range of chiral acids. However, silica gel can be modified by other chiral selectors, following the example of chromatographic fillings, and thus extend the applicability of membranes to other chiral compounds.

• Čížek J., Labíková M., Drobek M., Faur C., Mericq J.P., Koštejn M., Hrdlička Z., Stanovský P., Floreková J., Yalcinkaya F., Kohout M., Izák P.: High-performance enantioselective ion-exchange mixed matrix membranes based on PVDF and EVOH polymers with cinchona-derived chiral silica particles. J. Membr. Sci. 2025, 733(Sept 2025), 124376. doi.org/10.1016/j.memsci.2025.124376