Isoreticular Contraction of kgd-Topology Covalent Organic Framework Membranes for Precise Pharmaceutical Separation

Covalent organic frameworks (COFs) provide a structurally programmable platform for membrane-based separation of small-molecule active pharmaceutical ingredients (APIs). Nevertheless, constructing membrane pores with subnanometer precision and resolving structurally similar molecular mixtures remain major challenges. Herein, we report an isoreticular contraction strategy to construct a series of kgd-topology COF membranes with progressively narrowed apertures in situ on polyacrylonitrile (PAN) substrates through contra-diffusion interfacial polymerization between hexa(4-formylphenyl)benzene (HFPB) and three triamine monomers of decreasing size. Systematic framework contraction decreased the aperture from 12.1 to 10.2 Å and then to 6.5 Å, giving molecular weight cut-offs of 500, 380, and 290 Da, respectively. Notably, membranes with different contraction degrees were further integrated into a cascade separation system with well-separated molecular-weight rejection thresholds, enabling the purification of a four-component mixture of camptothecin-related compounds with equal mass concentrations, achieving a maximum fraction purity of 96.6%. This work establishes isoreticular contraction as an effective strategy for programming transport-relevant pores in COF membranes and highlights the potential of kgd-topology COF membranes for cascade pharmaceutical purification.