New polymeric receptors : microgels and RAFT copolymers, their synthesis and supramolecular binding to low-molecular-weight compunds and proteins

Abstract

The aim of this thesis is to explore the use of microgels and linear copolymers as supramolecular receptors for low molecular weight compounds and proteins. It was postulated that the long-range interactions made possible by repeating units within a polymer would be advantageous in creating high affinity supramolecular hosts in a competitive aqueous environment. Tetrazoles frequently replace carboxylic acids in pharmaceutical drugs, their binding to amidines was investigated as a model system to determine their exact mode of interaction with an arginine analogue, where there has been some ambiguity in the literature regarding the preferred binding sites for tetrazolates. 1H NMR studies and crystal structures of model complexes were used to investigate their interactions. A preference for protonated amines over guanidine-like amidines was observed, it was postulated that this would infer a degree of selectivity to microgels and linear copolymers incorporating the tetrazolate functional group. Microgels and linear copolymers were synthesised and investigated using 1H NMR, UV-Vis and ITC titrations to determine their affinity for selected ligands, such as the biologically significant polyamine spermine and proteins such as haemoglobin and cytochrome C. A living free radical polymerisation (RAFT) process was used to create linear copolymers with defined molecular weights and low polydisperisties. Evidence for the microgels and linear copolymers binding to the target molecules will be discussed. Evidence for the structural manipulation of the polymers, via dynamic combinatorial chemistry, to create highly specific hosts will be presented and discussed.Engineering and Physical Sciences Research Council (EPSRC