Chiral Ligand Exchange Adsorbents for Amines and Underivatized Amino Acids: 'Bait-and-Switch' Molecular Imprinting

Abstract

Ligand-exchange adsorbents for the chiral separation of underivatized α-amino acids and amine analogs have been prepared by molecular imprinting with a polymerizable copper complex and the amino acid as template. Because the complexation equilibria in these mixed-ligand systems involve numerous species, it is extremely important to characterize the template:monomer assemblies prior to polymerization. Isothermal titration calorimetry and classical species distribution diagrams have been used to determine the conditions under which the amino acids (phenylalanine) form strong 1:1 mixed-ligand complexes with the copper-iminodiacetate (CuIDA) functional monomer. In contrast, a diamine template ethylenediamine does not form 1:1 complexes with CuIDA; the diamine instead competes with IDA for the metal ion, and a stronger chelating group is required. Adsorbents prepared using enantiomers of phenylalanine as template show enantioselectivity for phenylalanine and tyrosine as well as for a chiral amine analog of phenylalanine, α-methylphenethylamine. The use of the amino acid as the template in this 'bait-and-switch' imprinting approach allows creation of chirally selective binding sites suitable for separations of chiral amines.