[Truncated] The work presented herein is the result of a study into the chemistry, spectroscopic properties and subcellular distribution of some gold(I) complexes of pharmacological interest. The thesis body is divided into two sections; the synthesis, characterisation, spectroscopy and biological activity of some potential anticancer compounds, dinuclear gold(I) N-heterocyclic carbene (NHC) complexes with bridging bidentate cyclophane ligands; and an investigation into novel methods for mapping the subcellular distribution of Au(I)-based anticancer compounds.
A series of symmetrical and asymmetrical azolium salts was synthesized as ligand precursors for dinuclear Au(I)-NHC complexes, the structures of which were characterised by X-ray crystallography, and variable temperature 1H NMR spectroscopy experiments in solution. Highly fluxional behaviour was found for all the azolium cyclophanes in solution. All of the cyclophanes were designed in such a fashion to afford modification of the lipophilic/hydrophilic balance, and control over the short intramolecular Au(I)•••Au(I) distance in the resultant dinuclear Au(I) complexes, to allow for their mapping inside cancer cells by fluorescence microscopy.
A series of dinuclear Au(I)-NHC complexes was synthesised using asymmetrical azolium cyclophanes as ligand precursors, resulting in the generation of two isomeric forms of each dinuclear Au(I)-NHC complexes. As such, six novel Au(I) complexes are presented, with the isomerism of each determined by X-ray crystallography. In the solid state all of the complexes had short Au(I)•••Au(I) contacts < 3.5 Å, and exhibited solvent and anion dependent photophysical behaviour. Additionally, an interesting trinuclear Au(I)-NHC complex was synthesised using a tetrakis imidazolium derived tetraphane as the ligand precursor, resulting in a complex which had short Au(I)•••Au(I) contacts determined by X-ray crystallography, and exhibited fluorescence in aqueous solutions.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - Sep 2010|