Novel Dissymmetric Copper Bis(thiosemicarbazone) Complexes for Medical Diagnostic Imaging by Positron Emission Tomography.

Brown, Oliver (2015) Novel Dissymmetric Copper Bis(thiosemicarbazone) Complexes for Medical Diagnostic Imaging by Positron Emission Tomography. Doctor of Philosophy (PhD) thesis, University of Kent,. (Full text available)

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Abstract

Bis(thiosemicarbazone) ligand derivatives and their metal complexes have long been of interest as they have applications as anticonvulsants, super-oxide dismutase-like radical scavengers, in the investigation of Alzheimer’s disease and diagnostic imaging. Copper (II) bis(thiosemicarbazone) derivatives have been used extensively in the imaging of oxygen deficient (hypoxic) cells for the detection and imaging of cancerous tissues and heart disease via Positron Emission Tomography (PET). It is possible to fine tune the bis(thiosemicarbazone) complexes redox potentials and lipophilicity by altering the substituents on the Q1 and Q2 position and the R1, R2, R3 and R4 locations respectively. To date only symmetric bis(thiosemicarbazone) ligands (R1=R3, R2=R4) have been evaluated for hypoxia imaging. This thesis reports the synthesis of dissymmetric ligands (R1≠R3, R2≠R4) in order to gain further control of the properties of the complexes and therefore the locations they will migrate to. A range of ligands has also been synthesised for the monitoring of copper metabolism within the brain for the investigation of Alzheimer’s disease and other neurodegenerative disorders. Ligand synthesis has been achieved by controlling the condensation reactions between dicarbonyl compounds and 4-substituted-3-thiosemicarbazides. Synthesis via an alternative acetal protecting method has also been investigated. Thirty bis(thiosemicarbazone) ligands have been successfully synthesised, of which thirteen are symmetric and seventeen dissymmetric. From this library of ligands, eighteen copper complexes have been synthesised along with twenty zinc complexes. The zinc complexes have the potential to act as convenient precursors for the rapid synthesis of radio-copper complexes via a transmetalation method. All ligands, complexes and intermediates have been fully characterised by a range of techniques including IR spectroscopy, Raman spectroscopy, NMR spectroscopy, UV-vis spectroscopy, elemental analysis and mass spectroscopy. A new cyclic by-product from the ligand synthesis has also been isolated and fully characterised.

Item Type: Thesis (Doctor of Philosophy (PhD))
Uncontrolled keywords: Bis(thiosemicarbazone), Copper, Diagnostic imaging, Dissymmetric, Hypoxia, Positron Emission Tomography, Zinc.
Subjects: Q Science
Q Science > QC Physics
Divisions: Faculties > Sciences > School of Physical Sciences
Depositing User: Users 1 not found.
Date Deposited: 05 Jan 2016 14:00 UTC
Last Modified: 01 Jul 2018 23:00 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53590 (The current URI for this page, for reference purposes)
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