New chelating systems for radiopharmaceutical diagnosis
This thesis concerns the design of novel binding agents for radioisotopes having potential application in radiopharmaceutical imaging systems. The first section reviews the currently available methods of radioimaging with particular emphasis on the limitations of the pharmaceutical reagents currently used for this important medical diagnostic tool. The main focus of the work concerns: (i) the design and study of a particular class of novel radiopharmaceutical hosts based on a well-established group of polydentate ligands, the propylene amine oximes (PnAOs); and (ii) the evaluation of various techniques for the quantification of host binding efficiency. Modelling studies have been used to design a series of novel, multi-functional PnAO complexes of Tc(V). In particular, substitution of the PnAO skeleton with pendant arms containing hetero-atom substituted aromatic rings was investigated with a view to increasing the co-ordination number of the ligand, thereby leading to complexes which would be more stable within the body. Six novel PnAO ligands substituted with tethered methoxybenzene and pyridinyl moieties have been prepared and fully characterised. A number of these ligands have been successfully complexed with the Tc(V) mimicking metals Co(III) and Cu(II) and their crystal structures solved. Extraction experiments have been used to determine the strength of the association between polydentate ligand hosts and their metal guests. A series of oxonol dye salts based on the Tc(V) mimicking metals Mn(II), Co(III), and Cu(II) have been prepared in high purity. Their use as extraction experiment indicators was, however, precluded by the insoluble nature of the PnAO-oxonol salt complexes formed.