Synthesis of ruthenium and rhodium complexes for their use as anti-cancer agents and catalysts

This thesis is concerned with the synthesis and characterisation of a series of functionalised bis-picolinamide ruthenium and rhodium dihalide complexes that have the potential to be developed as anti-cancer agents and catalysts. Their structural characterisations and, anti-cancer and catalytic activities were explored and investigated.
There are more than thirty novel bis-picolinamide ruthenium dihalide complexes [RuX2L2] and six bis-picolinamide rhodium dihalide complexes [RhX2L2] (where X is chloride or iodide, and L is the functionalised bidentate picolinamide ligand) synthesised and fully characterised. X-ray crystallography showed the picolinamide ligands are bonded in N,N- and N,O- coordination modes to the metal centre. Three different geometries were seen for the dichloride complexes which were cis-cis-cis, cis-trans-cis and trans-trans-trans, whereas only the trans geometry was seen for the diiodide complexes. UV-Vis solution studies of the Ru complexes have shown no visible changes in the spectra over a range of days and temperature. Powder diffraction of Ru dichloride gave inconclusive data, however Ru diiodide complexes showed evidence of trans structural stability. As Ru(III) complexes are not amendable to study by NMR, Rh analogues were prepared to analyse their structural characterisation. The results have shown that there is a possible mixture of three different isomers within the Rh dichloride complexes, whereas the Rh diiodide only showed trans isomer, confirming that the diiodide complexes both for Ru and Rh are stable in structure conformations.
There has been much interest in developing new metal-based anti-cancer complexes since the successful discovery of cisplatin. Ru-based complexes have become one of the most promising groups of complexes, having cytotoxic properties but not significantly affecting normal healthy cells. Bis-picolinamide Ru dihalide complexes were tested against a variety of cancer cell lines to determine the cytotoxicity. It was found that the cytotoxicity increases when changing the halide ligands from dichloride to diiodide, and when the substituents on the phenyl ring of the ligands are meta or para chloro or bromo substituents. Complexes 4.8 and 4.13 are the two most promising anti-cancer complexes, which are potent both under normoxic and hypoxic conditions. Following the cytotoxicity studies, selected complexes were examined for hydrolysis and hydrophobicity. The most cytotoxic Ru dichloride complex hydrolyses more and undergoes the fastest hydrolysis, which is in contrast with Ru diiodide complexes, by which the most cytotoxic complex undergoes the least hydrolysis. There are very few correlations observed between the cytotoxicity and log P values of the Ru dichloride complexes, suggesting that the cell uptake mechanism may not relate to their cytotoxic anti-cancer activities. The ongoing research on catalytic transfer hydrogenation reaction is targeted towards metal catalysts that can favour high activity under mild operating conditions. Several bis-picolinamide Ru and Rh dihalide complexes were studied as catalysts in the reduction of benzaldehyde. The complexes that were selected for the studies have several components that can be used to investigate their structural-activity relationships. In general, the diiodide analogues of the catalysts are more active than the dichloride analogues. In combination of the dihalide ligands with the appropriate functionalised picolinamide ligands can improve their catalytic activities. There is a contrasting activity seen between Ru and Rh catalysts, whereby their catalytic activities are affected by different components of the catalysts. Ru catalyst may be largely affected by the different functionalised picolinamide ligands, whereas Rh catalysts have showed difference in activities when changing the X ligands.