Abstract
This project investigates the possibility to develop organometallic complexes of transition metals possessing biomedical applications, so as to develop potential theranostic agents. Specifically, this work describes the development of tripodal systems and their related metal complexes with relevance for prostate cancer diagnosis using cellular imaging techniques.Chapter 1 presents the context of this work. The concept of coordination compounds possessing biomedical applications is introduced, and a literature review regarding the latest transition metal complexes displaying biological activities is presented. Molecular imaging techniques are described together with examples of metal complexes designed for imaging applications. An overview of cellular hypoxia and its role in tumour development is given, along with a description of prostate cancer, its features and how these can be exploited in diagnosis and therapy.
Chapter 2 describes the syntheses of tripodal systems based upon a hexasubstituted benzene scaffold, and their potential for biomedical applications is probed. In this chapter, two series of nitrogen-based and one series of anthracene-thiosemicarbazone-based tripodal systems were successfully synthesised and characterised spectroscopically, and their biological activity probed with MTT assay and confocal microscopy experiments on PC3 prostate cancer cells.
Chapter 3 describes the development of a series of tripodal N-heterocyclic carbene-based compounds with the potential to act as ligands for a variety of transition metals. In this chapter, the synthesis and characterisation of nine tripodal systems, which incorporate unsymmetrical imidazole arms is described. Crystals suitable for X-ray diffraction were successfully obtained for four compounds described hereby, allowing an appreciation of how these systems present dynamic conformational equilibria, and are able to form polymeric associations via network of interactions between the tripodal systems and their anions.
Chapter 4 describes the syntheses of novel tripodal systems with unsymmetrical substituents, so to develop ligands capable of binding metals as well as other functionalities. The unsymmetrical tripodal systems presented in this work are based upon the tripodal NHC-based compound 76 described in Chapter 3, in which one of the three NHC arms is modified either with carboxylic acid-based linkers, as well as with the introduction of an anthracenethiosemicarbazone derivative.
Chapter 5 describes the complexation attempts between a series of transition metals that have known biomedical potential and selected tripodal systems discussed in the previous chapters. Two anthracene-thiosemicarbazone based tripodal systems, previously reported in Chapter 2, were metallated by exploiting microwave technology to obtain rhenium and ruthenium complexes. The development of metal complexes of group 11 transition metals and tripodal NHC-based ligands reported in Chapter 3 is discussed and their biological activities are probed in PC3 cells using MTT assays and confocal microscopy experiments.
Chapter 6 summaries the work described throughout the thesis and future work emerging from the project results.
Chapter 7 contains all the experimental details and characterisation data for the compounds obtained in this work.
The Appendices provide supporting spectroscopic data and X-ray diffraction data for the compounds developed during this project.
| Date of Award | 11 May 2020 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Sofia Pascu (Supervisor) & Ian Eggleston (Supervisor) |
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