MOLECULARLY IMPRINTED POLYMERS: TOWARDS RECEPTOR MIMICS FOR DRUG DISCOVERY

Molecularly imprinted polymers (MIPs) are molecular recognition materials composed of specific cavities
designed upon a template molecule. They are produced by copolymerization of functional monomers and a high
fraction of cross-linking agents in the presence of a template molecule. This work aims at developing a selective
chromatographic media based on MIPs for the screening of active components from natural products. In the field
of drug discovery, rigid imprint formation is not required since the MIPs should be able to recognize structural
analogues of the template.
In order to find a compromise between flexibility and rigidity, quercetin imprinted polymers (Qu MIPs) (Fig. 1)
were prepared by modifying the synthesis reagents composition. Corresponding control polymers (non-imprinted
polymers, NIPs), formulated in a similar fashion, without introduction of the quercetin template molecule, were
produced, treated and studied similarly than MIPs. Bulk polymerization (BP), precipitation polymerization (PP)
and suspension polymerization (SP) were investigated to obtain optimal chromatographic materials. Particles
size and shape were characterized by scanning electron microscopy (SEM) and/or transmission electron
microscopy. The MIPs were finally evaluated as sorbents for solid-phase extraction (SPE) and HPLC.
The HPLC selectivity study towards analogues and non-analogues of the template molecule quercetin (Qu)
allowed to confirm the modulation of flexibility thanks to original synthesis strategies. Successful imprinting
was confirmed by SPE since the retention of quercetin appeared distinctly superior on MIPs than on NIPs. The
best SPE results were obtained for MIPs prepared by the SP method. The micrographs obtained by SEM
revealed a large distribution of sizes and irregular shape of the particles prepared by BP. Oppositely, spherical
beads having a homogeneous size distribution were obtained by SP. The SP approach appeared therefore as the
most attractive because it produces polymer beads with a considerable yield and improved chromatographic
characteristics.