β-Cyclodextrin covalent organic framework modified-cellulose acetate membranes for enantioseparation of chiral drugs

Abstract

Membrane-based chiral separation has attracted widespread research attention. However, traditional chiral membranes remain an unbridgeable trade-off between permeability and selectivity. Chiral covalent organic frameworks (CCOFs) with inherently high porosity and intrinsic chirality are highly promising solutions. Herein we report novel CCOF membranes for enantioseparation of chiral drugs. A β-cyclodextrin covalent organic framework (β-CD COF) was used as the chiral selector to fabricate two types of β-CD COF membranes by physically and chemically modifying cellulose acetate substrates, including a β-CD COF mixed matrix membrane (β-CD COF MMM) and a β-CD COF thin film nanocomposite membrane (β-CD COF TFN). In particular, the β-CD COF TFN was the first reported interfacial polymerized COF membrane for enantioseparation and performed more preferentially than β-CD COF MMM. The optimal enantioselectivities of d, l-tryptophan (e.e% = 100%), (RS)-mandelic acid (e.e% = 58.1%), d, l-phenylalanine (e.e% = 36.3%), and (RS)-propranolol (e.e% = 18.0%) and comparable solute flux (Flux = 1.9–5.4 nmol·cm−2·h−1) were achieved using β-CD COF TFN. Benefiting from the remarkable chemical stability of β-CD COF, such membranes also had excellent thermal stability, acid resistance, and long-term storage stability. Moreover, the chiral recognition mechanism was investigated using molecular docking simulations. Fabricated membranes with high enantioseparation performance and stability provide a new perspective on establishing chiral membranes and show potential for industrial application.