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Synthesis, Characterisation, and Development of Photo-activated Carbon monoxide-releasing Molecules

Ward, Jonathan S (2014) Synthesis, Characterisation, and Development of Photo-activated Carbon monoxide-releasing Molecules. PhD thesis, University of York.

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Abstract

Several series of photo-activated carbon monoxide-releasing molecules have been synthesised and characterised for use as potential pharmaceutical molecules. Initial CO-RMs synthesised were based on a tetracarbonyl phenylpyridine(I) complex, with substitutions in the para-phenyl position. All were shown to release CO when irradiated with light of wavelength 365 nm. An LED system was developed to irradiate samples in CO-release quantification assays. A carboxylic acid-containing CO-RM was then developed to improve solubility. The new CO-RM is water compatible and releases three molecules of CO per molecule of CO-RM. It has been shown to be viable with sensitive RAW 264.7 macrophage cells, and to exhibit a toxic effect on E. coli in combination with light of wavelength 400 nm. An L tryptophan-containing CO-RM was synthesised and is water compatible; and releases CO when irradiated at 465 nm light. It is viable with RAW 264.7 cells and is capable of suppressing an inflammatory response initiated by LPS and IFN-γ and been shown to have a detrimental effect on E. coli, S. aureus, and N. gonorrhoeae. An alkyne-containing CO-RM was designed so that it could be used in Huisgen [3+2] cycloaddition chemistry. This CO-RM was functionalised using 4-azidobenzoic and biotin to give two new triazole-containing CO-RMs. The biotin-containing CO-RM has been shown to release CO and bind strongly with an avidin target. Bacterial studies with a tryptophan-containing CO-RM show that increased optical density of cultures decreases the effectiveness of the CO-RM, due to reduced light penetration. This lead to the development of dye-containing CO-RM, which is based on a benzothiazole azodye. This dye-CO-RM contains a UV-band associated with CO-release that tails out to a higher wavelength than any of the previous CO-RMs prepared in this project.

Item Type: Thesis (PhD)
Academic Units: The University of York > Chemistry (York)
Depositing User: Mr Jonathan S Ward
Date Deposited: 02 Dec 2014 12:46
Last Modified: 20 Nov 2016 01:18
URI: http://etheses.whiterose.ac.uk/id/eprint/7372

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