Molecularly imprinted ligand-exchange adsorbents for the chiral separation of underivatized amino acids

Ligand-exchange adsorbents that are enantioselective for underivatized α-amino acids have been synthesized by molecular imprinting using only achiral monomers. Bulk polymers were prepared by allowing the functional monomer, Cu(II)–N-(4-vinylbenzyl)iminodiacetic acid, to form complexes with the template amino acid in solution, followed by crosslinking with ethylene glycol dimethacrylate. To make supports suitable for chromatography, the imprinted polymer was grafted to derivatized silica particles. Racemic mixtures of various underivatized α-amino acids are resolved on the imprinted adsorbents. Adsorbents prepared from amino acids with larger, aromatic side chains exhibit the highest selectivities (α=1.65 for the enantioresolution of d,l-phenylalanine). Cross-selectivity for similar amino acids also depends on side chain size: materials templated with l- or d-phenylalanine exhibit good enantioselectivity when challenged with racemic tyrosine (α∼1.4) and much reduced enantioselectivities towards d,l-tryptophan or aliphatic amino acids. Materials imprinted with alanine show no selectivity. The ability of a material imprinted with an amino acid enantiomer to resolve an analogous chiral amine is also demonstrated. The mechanisms underlying the observed enantioselectivity are discussed in light of the three-point interaction model for conventional chiral ligand-exchange separations.