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Title: Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications
Author: Atkin, Anthony John
ISNI:       0000 0004 2720 8813
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2010
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The administration of carbon monoxide (CO) to living systems has been found to elicit beneficial therapeutic responses in many different applications. In order to deliver CO safely and controllably at concentrations able to provide these positive effects, the use of carbon monoxide-releasing molecules (CO-RMs) has been developed. This thesis details the discovery of new classes of metal(O)-containing organometallic CO-RMs, their ability to release CO and their therapeutic action. Hexacarbonyl(~l2-alkyne)dicobalt(O) complexes were highlighted as potential CO- RMs. By varying the substituents on the alkyne ligand, a range of CO-release rates in aqueous media were obtained. The amount of CO released from these CO-RMs was quantified by use of a myoglobin biochemical assay. Study into the solution behaviour of these CO-RMs in DMSO/water mixtures revealed the importance of a cobalt-cobalt disproportionation reaction and also the reactivity of amino acid residues on the release rate. A selection of the hexacarbonyl(μ2-alkyne)dicobalt(O) were tested against biological systems in order to assess their therapeutic potential. Experiments with murine macrophages revealed the toxicity, the effect on the cell viability and the anti- inflammatory effect elicited by these CO-RMs. Further studies demonstrated the ability of members of this class of CO-RMs to inhibit the growth of the bacteria Pseudomonas aeruginosa. Studies on tricarbonyl(ή4-diene)iron(0) structures provided further successful CO- RMs when the diene ligand used was norbomadiene. In addition to this, tetracarbonyl(ή4-norbomadiene)chromium(O) and molybdenum(O) complexes also released CO in the myoglobin assay. Through substituent variation on the organic ligand it was found that the strength of the iron-diene bonds in the tricarbonyl(ή4- diene)iron(O) complexes was a significant factor in controlling the rate of CO-release from this class of CO-RM; complexes with weaker metal-diene bonds were generally faster CO-releasers.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available