Dual-charged dense COF membranes for efficient removal of low-molecular-weight pharmaceuticals

Traditional nanofiltration (NF) membranes exhibit low rejection ratios for low-molecular-weight (LMW) or positively charged pharmaceuticals owing to broad pore size distributions and negatively charged surface. Covalent organic frameworks (COFs) are highly promising for membrane fabrication due to their tunable pore functionality and adjustable pore sizes. Herein, dual-charged COF membranes were fabricated via sodium dodecyl sulfate (SDS)-mediated interfacial polymerization (IP), followed by polyethyleneimine (PEI) crosslinking to improve the removal of LMW or positively charged pharmaceuticals. In the SDS-mediated IP process, the reduction of pore size from 0.387 ± 0.60 nm (COF 0-10 membrane fabricated without SDS) to 0.269 ± 0.54 nm (COF 0.25-10 membrane) led to a substantial improvement in Na 2 SO 4 rejection ratio from 43.9 % to 81.4 %. Furthermore, PEI crosslinking with residual free -CHO groups on the COF 0.25-10 membrane surface enhanced size sieving and electrostatic interactions while preserving membrane crystallinity. The optimized COF 0.25-10 -PEI 0.2-2.5 membrane with the pore size of 0.209 nm demonstrated exceptional rejection ratios (>87 %) for five representative pharmaceuticals with different properties. Among them, the optimized COF 0.25-10 -PEI 0.2-2.5 membrane showed superior rejection ratio of 92.6 % for the positively charged and LMW (129.16 Da) metformin. Compared to the pristine COF 0.25-10 membrane without PEI crosslinking, the resulting COF-PEI membranes demonstrated 3.8-6.5 folds improvement in pharmaceutical rejection, particularly for challenging LMW and positively charged pharmaceuticals, owing to the synergistic effects of size exclusion and electrostatic interactions. Furthermore, mechanistic study revealed that SDS in aqueous phase promoted faster and more uniform diffusion of TG Cl monomers, enhancing the crystallinity of the TpTG Cl -COF membranes and improving the pore uniformity, while PEI crosslinking further narrowed the pore size and obtained dual- charged COF layer. This study provides a new paradigm for designing charge-tunable and crystalline COF membranes for precision separation of LMW pharmaceuticals.