This thesis concerns the synthesis of a number of bis(phenyl-l ,3-~- diketonato )titanium dihalide complexes, and their subsequent evaluation as anticancer drugs in vitro. Mechanistic work has been carried out to determine the mode of anticancer activity exhibited by this class of drugs. Chapter 1 gives a summary of research into metal-containing anticancer drugs to date, with particular emphasis on the role of titanium. Chapter 2 describes the synthesis and characterisation of a series of phenyl-l,3-~- diketonate ligands, and the synthesis and characterisation of a bis(phenyl-l ,3-~- diketonato )titanium ethoxide complex. Chapter 3 describes the synthesis' and characterisation of six bis(phenyl-l ,3-~- diketonato)titanium dichloride complexes and SIX bis(phenyl-l,3-~- diketonato )titanium dibromide complexes. Chapter 4 describes in vitro testing carried out on a senes of bis(phenyl-l ,3-~- diketonato )titanium dihalide and dialkoxy complexes using the MTT assay with varying incubation times and oxygen concentrations. Several complexes are shown to exhibit cytotoxicity comparable to cisplatin. Chapter 5 describes a number of mechanistic studies carried out using the bis(phenyl-l ,3-~-diketonato )titanium complexes, and presents evidence for a cytotoxic species consisting of titanium with both diketonate and DMSO ligands. Chapter 6 gives experimental details and characterisation data for the compounds described in Chapters 2-5.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:550321 |
| Date | January 2011 |
| Creators | Crossley, Benjamin David |
| Publisher | University of Leeds |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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