Imprinted polymers for chiral resolution of (±)-ephedrine. Part 2: probing pre-polymerisation equilibria in different solvents by NMR

Abstract

A sophisticated analysis of the pre-polymerisation association of monomer and template for the molecular imprinting of (−)-ephedrine (template) using methacrylic acid (monomer) has been performed using NMR titrations and data analysis with the computer program HypNMR. The fitted model takes account of the dimerisation of monomer, and 1 : 1, 2 : 1 and 3 : 1 monomer–template complexes. Values for the association constants and chemical shifts of the different nuclei in the various species are generated quickly and simply. The speciation has been compared in chloroform, toluene and acetonitrile, and in the absence and presence of cross-linking monomers. The 1 : 1 monomer–template interaction is very strong in all three solvents, such that 1 : 1 mixtures contain an almost stoichiometric amount of 1 : 1 complex. Imprinted polymers made with different monomer–template ratios have been used in the enantioseparation of (±)-ephedrine and confirm the utility of the 1 : 1 complex for the formation of effective recognition sites.