Molecularly imprinted polymers: new synthesis strategies for drug innovation

This study aims at developing a drug screening approach based on molecularly imprinted polymers (MIPs).
MIPs are synthetic molecular recognition elements which possess specific cavities designed for a single template
molecule. However, MIPs used as drug discovery tools should exhibit selectivity towards compounds carrying a
congruent pharmacophore instead of an absolute specificity for a template. In this work, we developed
innovative synthesis strategies consisting in grafting polyethylene glycol (PEG) moieties on the imprinted
cavities of quercetin-imprinted polymers (Qu MIPs).
The Qu MIPs were prepared by bulk polymerization and by precipitation polymerization using quercetin as
template molecule, acrylamide (AA) as functional monomer and ethylene glycol dimethacrylate (EDMA) as
cross-linker with tetrahydrofuran (THF) as porogen. Corresponding control polymers (non-imprinted polymers,
NIPs), formulated in a similar fashion, but without introduction of the template molecule, were treated and
studied in the same way as the MIPs.
The presence of imprinted cavitites was confirmed by evaluating the Qu MIPs as solid-phase extraction (SPE)
sorbents. High Imprinting Effect (IF = Rate of retention on the MIP / Rate of retention on the NIP) values (>3)
were obtained attesting the successful imprinting of the Qu MIPs.
Qu MIPs were then evaluated by HPLC which allowed to confirm the modulation of selectivity obtained thanks
to the original synthesis strategies developed. Indeed, these new Qu MIPs exhibited a selectivity extended
towards a group of structural analogs; they similarly retained the flavonoids quercetin, naringenin and daidzein
but not the distantly related polyphenol curcumin.
Scanning electron microscopy (SEM) micrographs of Qu MIPs revealed a high irregularity in the shape of the
particles synthesized by bulk polymerization. On the contrary, spherical beads could be observed by synthetizing
the Qu MIPs by precipitation polymerization which should contribute to improve their chromatographic
separation efficiency.