Towards the Rational Design of Molecularly Imprinted Polymers

Molecular imprinting is a technique by which polymeric materials selective for a given target molecule can be created through a casting procedure. Functionalised monomers are added to a solution of molecular templates. Monomer-template complexes are formed and subsequently fixed through polymerisation, and following removal of the template species from the resultant molecularly imprinted polymer, MIP, a material containing binding sites able to specifically rebind the template is left. The objective of the present work has been to learn more about the mechanisms leading to the formation of selective binding sites in MIPs and the nature of these sites (1-3), with the goal to utilise this knowledge to develop better MIPs (4-7). 1) UV spectroscopic studies of the pre-polymerisation mixture were utilised to estimate the stabilities of monomer-template complexes under different conditions. It was observed that many templates are not fully complexed by monomers, possibly leading to different binding site populations. Such heterogeneity is indeed observed in MIPs. The method developed was found useful for rapid evaluation of different monomers or conditions for a given template. 2) Chromatographic studies were performed on polymers imprinted with various pyridyl templates. It was demonstrated that electrostatic interactions were those mainly responsible for binding in these systems. It was also demonstrated that free rotors in the template structure affected binding and selectivity negatively, and that the accessibilities of functional groups were essential for the utility of the template for molecular imprinting. 3) Load capacity studies of nicotine and 4,4´-bipyridyl MIPs revealed two different behaviours. The retention of 4,4´-bipyridyl decreased upon raising the sample load, but nicotine exhibited an increase. Two possible explanations to this unexpected effect were suggested: mobile phase related nicotine solvation effects or a type of cooperative binding. A maximum in resolution for the separation of (+/-)-nicotine at different sample loads indicated the presence of recognition sites for template-template complexes, implying the possible imprinting of template-template complexes. 4) A chiral tartaric acid based monomer was synthesised and employed for the imprinting of cinchona alkaloids. The chirality of the monomer was shown able to enhance selectivity for certain templates. Post-polymerisation debenzylation of the MIP enhanced both retention and selectivity due to a change from hydrogen bond interactions to ionic interactions. 5) Crown ethers were employed as co-templates in molecular imprinting to demonstrate a principle by which organic solvent non-solubles can be solubilised, and imprinted, in organic media. Rebinding studies in the absence of crown ether revealed imprinting related selectivity. 6) Imprinting in water was achieved through the introduction of a hydrophilic cross-linker, a highly acidic monomer, and a beta-cyclodextrin based monomer, able to interact by hydrophobic interactions with aromatic ring structures. By this approach, the enantiomers of phenylalanine were successfully imprinted. 7) A series of monomer combinations were evaluated to optimise the polymer system described in (6). Binding site hydrophobicities were examined by fluorescence spectroscopy. This thesis demonstrates that there is significant room for improving the performance of MIPs and points to some ways by which this can be achieved.