Synthesis and application of novel paramagnetic contrast agents for magnetic resonance imaging

Tyramide signal amplification is a technique used in microscopy experiments whereby phenol-bearing reporter molecules (containing, for example, fluorophore or heavy metal atoms, for use with fluorescence and electron microscopy respectively) are deposited in the vicinity of a target via an antibody-linked horseradish peroxidase-mediated coupling reaction. A paramagnetic lanthanide complex with a phenolic functionality was synthesised in order to adapt the method for use with MRI, and the process has been shown to be practicable both in model systems and in biological samples. A system has been developed so that chromatography experiments can be imaged with minimal disturbance to the column while it is in the MRI scanner and used to demonstrate measurements on ion exchange columns. Spin-labelled sugars were synthesised, with the intention of visualising the affinity chromatography process; these proved to be at the limit of detectability as relaxivity agents at the required concentrations. The affinity chromatography process was successfully imaged however, using the paramagnetic properties of Mn2+ ions bound to concanavalin A to provide the necessary image contrast. Stable nitroxide free radicals were synthesised to study the effect of charge-magnitude and -separation on proteoglycan affinity. It was demonstrated that species with greater positive charge had a greater affinity for articular cartilage. A brief investigation into the effect of nitroxides on the action of horseradish peroxidase was also carried out; they were found to act as non-competitive inhibitors.EThOS - Electronic Theses Online ServiceGBUnited Kingdo