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Synthesis of novel functionalised β-ketoiminate and β-diketonate metal complexes for their use in anti-cancer treatment

This thesis is concerned with the synthesis, characterisation and evaluation of novel metal complexes for their application as anti-cancer agents. It contains the in vitro cell results, along with a range of other techniques to determine their biological relevance and their potential as anti-cancer agents. Chapter 1 contains an introduction to the project including a literature search, previously synthesised complexes and project aims Chapter 2 presents the synthesis and characterisation of novel β-diketonate and β-ketoiminate ligands. X-ray crystallographic data are analysed for some of the ligands. Chapter 3 discusses the synthesis and characterisation of novel β-ketoiminate ruthenium chloride complexes. X-ray crystallographic data are analysed for all of the complexes. Chapter 4 introduces the MTT technique for assessing cytotoxicity, and presents in vitro activities for the library of complexes synthesised in Chapter 3. Chapter 5 looks at modifications of the previous ruthenium (II) complexes, introducing new ligands and iridum metal centres. X-ray crystallographic data for all of these complexes has been discussed, along with in vitro activity against a range of cell lines. Chapter 6 introduces hypoxia and states the cytotoxicities of a range of complexes under 1.0% and 0.1% oxygen concentrations. Chapter 7 discusses mechanistic studies on the complexes, including hydrolysis, hydrophobicity, Comet assay, apoptosis and thioredoxin reductase inhibition. Chapter 8 introduces the previous group IV work within the group and an extension of the library by synthesis of β-ketoiminate titanium complexes. X-ray crystallographic analysis is discussed where applicable. Chapter 9 contains experimental details and characterisation data for all compounds described in Chapters 2, 3, 5 and 8. Also protocols for all the biological studies. Appendix presents a summary of X-ray crystallographic structure analysis for any crystals obtained within this work.
Date January 2014
CreatorsLord, Rianne Michaela
PublisherUniversity of Leeds
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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