Macrocycle-Enabled Nanofiltration for Amino Acid Separation

Membrane-assisted peptide synthesis requires selective membranes capable of separating small, structurally similar molecules in organic solvent media. Efficient separation from low-molecular-weight impurities is critical for improving yield, enabling reagent recycling, and enhancing the overall process competitiveness. In this work, thin-film composite membranes fabricated from bis(aminobenzo)-18-crown-6 (18C6) and amino-functionalized β-cyclodextrin were evaluated, using multicomponent amino acid mixtures and piperidine as a model low-molecular-weight impurity. In aqueous systems, the 18C6 membrane rejected 92–96% of amino acids, while the Am7CD membrane showed nearly complete amino acid rejection. Both macrocycle-based membranes exhibited significantly lower rejection of piperidine, with Am7CD reaching a selectivity value of 1104 for leucine/piperidine separation. Amino acid rejection remained relatively stable across pH 3–11, while bulky aromatic amino acids such as tryptophan, tyrosine, and phenylalanine consistently exhibited higher rejection than smaller and more flexible amino acids, particularly in N, N -dimethylformamide containing media where an overall decrease in rejection was observed. These trends indicate that separation is likely governed by size exclusion and solvation effects with negligible electrostatic contribution.