Synthesis, characterisation and evaluation of biphenyl monomers for molecular imprinting applications

This work was spearheaded with the synthesis of seven novel biphenyl monomers possessing a range of acidic and basic functional groups using Suzuki cross-coupling reactions. Application of microwave heating has significantly improved the reaction yield in a short period, i.e., 30.0 min, whilst suppressing the homocoupling and Heck-coupling side reactions. The optimised microwave conditions have been adapted to large-scale synthesis of the biphenyl monomers and routinely used throughout this research. The aqueous acid dissociation constants of the biphenyl monomers were derived from the semi-aqueous potentiometric titration method developed in this research specifically for these sparingly water-soluble compounds. The first aqueous pKa values of these novel biphenyl monomers, ranging from pH 3-11, are reported herein. The biphenyl monomers were first used as functional monomers in the preparation of molecularly imprinted polymers for test targets theophylline and phenylphosphonic acid (PPA) by thermal and microwave (MW) polymerisation. Results of the semi-empirical molecular modelling and ¹H and ³¹P NMR titrations for theophylline and PPA, respectively, identified 4’-vinyl-biphenyl-4-ol (M2) as the best monomer to use for the synthesis of both theophylline and PPA MIPs. Both thermal and MW theophylline and PPA MIP systems prepared using M2 showed significant imprinting effect as confirmed by Freundlich analysis of their binding properties but the microwave polymers exhibited higher template uptake than their thermal counterparts, attributed to its high microporosity and lower surface charge. Cross-reactivity and selectivity tests with caffeine applied to the theophylline MIP system also showed the MW MIP to be more selective to the template (theophylline) than the competing analyte (caffeine) than the thermal MIP. The mode of polymerisation and nature of the porogen were observed to affect the physical properties of the polymers. MW polymers showed higher porosity, lower surface charge and lower surface area than their thermal equivalents. Polymers prepared in THF also exhibited higher porosity and higher surface area than those prepared in DMF.