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

Overview

A voltage-driven in situ assembly strategy constructs homochiral hydrogen-bonded biohybrid frameworks within poly(ethylene terephthalate) nanochannels for enantioselective amino acid separation. The membrane architecture integrates bovine serum albumin and 1,3,6,8-tetra(terephthalic acid) pyrene through directional hydrogen bonding to establish chiral microenvironments with enhanced structural stability.

Methods and approach

Homochiral nanochannel membranes were fabricated using voltage-driven in situ assembly of hydrogen-bonded biohybrid frameworks within PET nanochannels. The system exploits directional hydrogen bonding interactions between bovine serum albumin (chiral scaffold) and H4TBAPy (organic linker) to create a protein-guided framework. Enantioseparation performance was evaluated using racemic histidine, tryptophan, and arginine. Mechanistic analysis examined binding affinity and diffusion characteristics of enantiomeric species within the framework.

Results

The HBF@PET membrane achieved near-complete resolution of racemic histidine with enantiomeric excess exceeding 99%, transporting D-histidine at 4.52 ± 0.04 mmol m-2 h-1, representing elevated flux relative to existing nanochannel systems. Mechanistic characterization demonstrated stronger binding affinity of the hydrogen-bonded framework for L-histidine, which suppressed its diffusion while enhancing D-histidine permeation. The membrane exhibited transferable enantioselectivity across tryptophan and arginine substrates, indicating broader applicability beyond model amino acids.

Implications

The voltage-driven assembly approach addresses structural instability and active site heterogeneity limitations in prior homochiral nanochannel designs. Integration of protein-guided hydrogen-bonded frameworks within confined nanopore geometries establishes a scalable platform for achieving high enantioselectivity concurrent with sustained flux, differentiating this architecture from conventional nanochannel membranes. The protein-ligand system enables tunable chiral recognition while maintaining framework robustness. Demonstrated applicability across multiple amino acid substrates supports potential deployment in pharmaceutical separation workflows requiring enantiomeric purity. The methodology establishes protein engineering within nanochannels as a design strategy for chiral separation systems requiring both selectivity and throughput.