Imaging and sensing carbon monoxide in biological environments using targeted, multimodal probes
File(s)
Author(s)
Bond, Tamzin
Type
Thesis
Abstract
Chapter 1 explores the literature surrounding targeted ligands for therapeutics and imaging, the fundamental principles of molecular imaging and finally the chemistry of carbon monoxide. Specifically, literature relating to the use of targeted imaging probes with optical and PET moieties has been highlighted. Furthermore, the role of endogenous carbon monoxide has been described and the current methods of carbon monoxide detection in air and in cells have been reviewed.
Chapter 2 describes the development of a range of probes that are capable of selectively targeting diseased cells through novel modifications to the vinyl ligand of a series of σ-vinyl ruthenium(II) complexes. The in vitro behaviour of the complexes was assessed and a good degree of selectivity and increased cellular uptake was seen upon modification.
Chapter 3 further develops the fluorogenic sensing capabilities of a ruthenium-based carbon monoxide detection system. A series of mono-substituted, π-extended 2,1,3-benzothiadiazole fluorophores were developed, which when coordinated to the ruthenium centre were partially quenched due to the heavy atom effect. The biological compatibility of these probes was increased through modifications to the vinyl substituent. The detection of carbon monoxide in vitro using the complexes was assessed and a fluorescence turn-on response was visible.
Chapter 4 investigates how the relationship between the ruthenium(II) complexes and carbon monoxide can be exploited in the development of a PET radiotracer. Preliminary radiochemical experiments yielded encouraging results, with results suggesting the potential of this approach to provide a synthetically rapid route to radiotracer production that requires minimal purification.
Chapter 6 provides the experimental details and characterisation for all compounds described in the previous chapters.
Chapter 2 describes the development of a range of probes that are capable of selectively targeting diseased cells through novel modifications to the vinyl ligand of a series of σ-vinyl ruthenium(II) complexes. The in vitro behaviour of the complexes was assessed and a good degree of selectivity and increased cellular uptake was seen upon modification.
Chapter 3 further develops the fluorogenic sensing capabilities of a ruthenium-based carbon monoxide detection system. A series of mono-substituted, π-extended 2,1,3-benzothiadiazole fluorophores were developed, which when coordinated to the ruthenium centre were partially quenched due to the heavy atom effect. The biological compatibility of these probes was increased through modifications to the vinyl substituent. The detection of carbon monoxide in vitro using the complexes was assessed and a fluorescence turn-on response was visible.
Chapter 4 investigates how the relationship between the ruthenium(II) complexes and carbon monoxide can be exploited in the development of a PET radiotracer. Preliminary radiochemical experiments yielded encouraging results, with results suggesting the potential of this approach to provide a synthetically rapid route to radiotracer production that requires minimal purification.
Chapter 6 provides the experimental details and characterisation for all compounds described in the previous chapters.
Version
Open Access
Date Issued
2021-10
Date Awarded
2022-02
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Wilton-Ely, James
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)