Synthetic cinchonidine receptors obtained by cross-linking linear poly(methacrylic acid) derivatives as an alternative molecular imprinting technique

Abstract

A molecular imprinting approach to construct synthetic receptors was examined, wherein a linear pre-polymer bearing functional groups for intermolecular interaction with a given molecule is cross-linked in the presence of the molecule as a template, and subsequent removal of the template from the resultant network-polymer is expected to leave a complementary binding site. Poly(methacrylic acid) (PMAA) derivatized with a vinylbenzyl group as a cross-linkable side chain was utilized as the pre-polymer for the molecular imprinting of a model template, (−)-cinchonidine. Selectivity of the imprinted polymer was evaluated by comparing the retentions of the original template, (−)-cinchonidine and its antipode (+)-cinchonine in chromatographic tests, exhibiting a selectivity factor up to 2.4. By assessment of the imprinted polymers in a batch mode, a dissociation constant at 20 °C for (−)-cinchonidine was estimated to be K d=2.35×10 −6 M (the number of binding sites: 4.54×10 −6 mol/g-dry polymer). The displayed affinity and selectivity appeared comparable to those of an imprinted polymer prepared by a conventional monomer-based protocol, thus showing that the pre-polymer, which can be densely cross-linked, is an alternative imprinter for developing template-selective materials. (−)-Cinchonidine-imprinted polymers were prepared and assessed using the pre-polymers bearing different densities of the vinylbenzyl group and different amounts of the cross-linking agent to examine the appropriate density of the cross-linking side chain that was crucial for developing the high affinity and selectivity of the imprinted polymers.