Development of molecularly imprinted polymers for amphetamine type substance recognition in aqueous environments

Amphetamine type substances are a legal concern for many jurisdictions across the world, and as such enforcement agencies require tools to easily identify these compounds in field settings. Synthetic receptors are an interesting tool for this purpose, and they come in many types. Of these varieties, Molecularly Imprinted Polymers are a cheap, fast, stable, selective and viable tool to perform this recognition. As compounds analogous to the amphetamine type substances are involved in the neuroregulation of homeostasis and stimulus respone in natural systems, the techniques and interactions used by natural systems may be mimicked in a synthetic environment to create bio-mimetic, synthetic receptors for amphetamine types substances. This work comprises of an initial phase of in silico screening where a library of commercially available monomers was screened against several amphetamine analogues to determine the identity and the number of functional monomers associated with the template molecules. Subsequently, in silico screening was carried out on these equilibrium geometry structures after freezing the monomer units in place to mimic the polymerisation step. Screening of a library of drugs and indicator substances was carried out to determine the direct interaction between functional monomer imprint site and the ligands. NMR investigations were carried out to confirm the interactions predicted in the initial screening and polymers synthesised in a variety of porogens to probe the effect of solvent on the polymerisation process. Subsequently, the synthesised polymers were introduced to the template in a variety of solvents to probe the adsorption behaviour of the polymers in a variety of solvents. Those which demonstrated the most selective behaviour in aqueous solution were subjected to varied techniques to optimise the selective adsorption of amphetamine type substances using both a pH buffer and ionic solution for the ionisable polymers and a dye displacement scheme to reduce the observable non-specific adsorption component of the interaction between analyte and adsorbent. A dye displacement motif was incorporated into the adsorption to reduce the non-specific binding component by reporting only specific binding events. Using this scheme, an imprinting factor “I” of 10.71 was obtained for ephedrine in aqueous solution by a methacrylamide co-EGDMA polymer at a T-FM ratio of 1-5 synthesised as a bulk monolith by thermally activated, free radical initiation in toluene.