Robust Homochiral Hydrogen-Bonded Biohybrid Nanochannel Membranes for High-Efficiency Enantioseparation of Amino Acids

Homochiral nanochannel membranes hold promise for scalable enantiomer separation, yet achieving high enantioselectivity with robust flux remains challenging due to structural instability and heterogeneous active sites. Here, we report for the first time a voltage-driven in situ assembly strategy to construct a homochiral hydrogen-bonded biohybrid framework (HBF) within poly(ethylene terephthalate) (PET) nanochannels (HBF@PET). Leveraging directional hydrogen bonding between bovine serum albumin and 1,3,6,8-tetra (terephthalic acid) pyrene (H 4 TBAPy), the membrane inherits BSA’s chiral microenvironment while achieving exceptional structural stability. The HBF@PET membrane enables near-complete resolution of racemic histidine (ee >99%) with d -His preferentially transported at a record flux of 4.52 ± 0.04 mmol m –2 h –1, surpassing state-of-the-art nanochannel systems. Mechanistic studies reveal stronger binding affinity of HBF for l -His, hindering its diffusion while facilitating d -His permeation. The membrane further demonstrates broad applicability to tryptophan and arginine enantiomers. This work pioneers the development of protein-guided hydrogen-bonded frameworks within nanochannels, offering a scalable platform for high-efficiency chiral separations in pharmaceuticals.