Molecular imprinting is a process of generating molecular recognition in the presence of a template during the formation of the three-dimensional structure of a polymer. Most imprinting to date has been carried out in a non-aqueous environment. Molecular imprinted polymers (MIPs) for the angiotension convertase enzyme (ACE) inhibitor lisinopril dihydrate and its structural analogues enalapril maleate and lisinopril DKP were synthesised utilising a non-covalent monolithic imprinting strategy in an aqueous porogen. These templates are highly functionalised with limited solubility in most polar and non-polar solvents. Selectivity for the imprinted over the non-imprinted polymers was demonstrated for all materials synthesised. A two monomer system was shown to be the optimum choice for polymer composition giving an imprinting factor of 8.3 using lisinopril dihydrate. Concentration of functional monomers and crosslinker was identified to be important factors in template extraction and polymer affinity. Methylmethacrylate was shown to function as an inert monomer impacting on polymer performance through its critical role in establishing polymer morphology. 4-vinyl pyridine interacted with the phenyl groups on the templates via π−π interactions. Ethylene glycol dimethacrylate served as a crosslinker giving structural rigidity to the polymer. Affinity and selectivity was achieved in water, methanol:water (4:1) and acetonitrile:methanol (1:3). Optimisation of loading conditions led to complete separation of the relevant templates from cited related substances. This is an important capability of the polymers as it has substantial implications for commercial applications such as sample clean-up and drug delivery. Scatchard plots, Langmuir, Freundlich and Langmuir- Freundlich isotherms were examined for suitability for use in examining the binding properties of the MIPs selective for lisinopril dihydrate. Binding studies were carried out in three different solvents. Langmuir-Freundlich and affinity distribution studies were found to be the most suitable for MIPs synthesised. Significant heterogeneity was revealed within the binding sites of the polymers studied which were reflective of polymer composition and affinity. Polymer morphology was examined through physical analysis using thermogravimetric analysis, differential scanning calorimetry, swelling ratio, particle size and surface area analysis. The relationship between crosslinker, functional monomer and template was examined through comparisons of solid phase extraction studies, binding isotherm data and physical properties of the MIPs. Differences in polymer affinity were related to binding site heterogeneity, polymer composition and physical characteristics of the polymers. Finally, polymer ruggedness was determined by comparison of the polymer affinity (imprinting factor) for template over a 59 month period to establish the practical robustness of this media. A 5% RSD in imprinting factor was observed. Differences were noted even though the polymers under went a series of solvent and selectivity studies that did not seem to impact the polymer specificity. This work showed that there is huge opportunity for further optimisation of the polymer selectivity and applications based on the large range of functional monomers coupled with controllable polymerisation conditions available.
|Publication status||Submitted - 2009|