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New derivatives of nitroimidazoles for the potential imaging and therapeutic treatment of hypoxic tissue

Alghamdi, Nuha 2019. New derivatives of nitroimidazoles for the potential imaging and therapeutic treatment of hypoxic tissue. PhD Thesis, Cardiff University.
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There is an increasing interest in the development of drugs able to selectively kill and target hypoxic cells. Hypoxic cells are known to exist in numerous tumours and prevent the successful treatment by both radiotherapy and chemotherapy. The goal of this work was to develop a hypoxia-sensitive imaging agent that would identify hypoxic cells based on 2-nitroimidazole or 5-nitroimidazole and compare the reduction potential of these nitroimidazoles. The development of drugs able of selectively killing the hypoxic cells was the additional aim for this research. In chapter 2, a series of novel luminescent compounds containing 2- nitroimidazole or metronidazole was synthesised as potential probes for use in confocal fluorescence microscopy. The luminescent properties of these compounds (the absorption and emission properties of the compounds) were investigated. The behaviour of these compound in cells were assessed using confocal fluorescence microscopy in order to determine the biological behaviour of these molecules in cells. In chapter 3 two novel ligands based on terpyridine and containing 2- nitroimidazole or metronidazole was successfully synthesised. A series of novel Fe(II),Co(II), Ni(II), Pd(II), Cu(II) and Zn(II) complexes of these two ligands was synthesised and fully characterised. The electrochemical behaviour of the ligands and complexes was to be studied using cyclic voltammetry to determine the suitability for their intended application. The synthesis of novel superparamagnetic iron oxide nanoparticles containing 2-nitroimidazole or 5-nitroimidazole were reported in Chapter 4. Fluorescently labelled (2/5) nitroimidazole conjugated to SPIONs were successfully synthesised as potential probes for use in MRI. The photophysical properties of these nanoparticles such as UV-vis and luminescence were investigated. iii Chapter 5 summarises the conclusions that may be drawn from the three previous chapters. In addition, it highlights future work that is needed for each of these areas of research.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Chemistry
Date of First Compliant Deposit: 14 January 2020
Last Modified: 26 Mar 2021 16:40

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