Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications

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 molecul...

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Main Author: Atkin, Anthony John
Published: University of York 2010
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Online Access:http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.556199
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spelling ndltd-bl.uk-oai-ethos.bl.uk-5561992015-03-20T05:37:09ZTherapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplicationsAtkin, Anthony John2010The 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.615.23University of Yorkhttp://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.556199Electronic Thesis or Dissertation
collection NDLTD
sources NDLTD
topic 615.23
spellingShingle 615.23
Atkin, Anthony John
Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications
description 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.
author Atkin, Anthony John
author_facet Atkin, Anthony John
author_sort Atkin, Anthony John
title Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications
title_short Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications
title_full Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications
title_fullStr Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications
title_full_unstemmed Therapeutic metal (0)-containing CO- releasing molecules : mechanistic insight and bioapplications
title_sort therapeutic metal (0)-containing co- releasing molecules : mechanistic insight and bioapplications
publisher University of York
publishDate 2010
url http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.556199
work_keys_str_mv AT atkinanthonyjohn therapeuticmetal0containingcoreleasingmoleculesmechanisticinsightandbioapplications
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