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dc.contributor.authorWalter, Melody Anna Rhine
dc.date.accessioned2017-03-30T04:30:51Z
dc.date.available2017-03-30T04:30:51Z
dc.date.issued2016-08
dc.identifier.otherwalter_melody_a_201608_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/walter_melody_a_201608_phd
dc.identifier.urihttp://hdl.handle.net/10724/36818
dc.description.abstractMetal-nitroxyl (M-HNO/M-NO-) complexes represent critical intermediates in the global nitrogen cycle. Free nitroxyl has pharmacological and therapeutic advantages distinct from NO•, such as the targeting of thiols and FeIII-hemes. HNO also increases heart muscle strength as a positive cardiac inotrope (increases myocardial contractility) and increases plasma levels of the calcitonin gene-related peptide (CGRP), whose cardiovascular effects include vasodilation. However, the rapid dimerization of HNO to N2O and H2O necessitates the use of donor molecules for HNO therapeutics. Current donors have limitations such as concomitantly releasing toxic by-products, short half-lives, and releasing NO•. There is a need for further development of HNO donors and improvement of our understanding of the fate of metal-nitroxyl complexes in the presence of relevant signaling agents, such as H+, O2, and RSH including H2S/HS-. Our efforts involve the rational design, synthesis, and development of {CoNO}8/9 complexes with N4 tetradentate supporting ligands for HNO delivery and investigation of the fate of Co-coordinated NO-. Given the paucity of literature on the reactivity of {CoNO}8 and {CoNO}9 complexes, we have investigated their ability to react with HNO targets such as PPh3 and [Fe(TPP)Cl] to afford Ph3PO/Ph3PNH or the {FeNO}7 porphyrin, respectively (Chapter 2). {CoNO}9 complexes also react with a water-soluble MnIII porphyrin and metmyoglobin to afford the corresponding nitrosylated species (Chapter 3). In organic solvents, {CoNO}8 complexes are unreactive in the presence of HNO targets; however, in the presence of a stoichiometric amount of protons, HNO reactivity is seen. In contrast, {CoNO}9 complexes react rapidly with HNO targets in both organic and aqueous media. These results indicate that {CoNO}8/9 complexes liberate HNO/NO- and serve as a potential platform for release of this therapeutic. Finally, we show H2S/HS--induced release of HNO from an otherwise unreactive {CoNO}8 complex in aqueous media (pH 7.4, 298 K; Chapter 4). These results indicate the key interplay of small molecules mediated at a metal center. Described in this dissertation are the synthesis, characterization, and reactivity studies of a series of {CoNO}8/9 complexes, which indicate their utility as HNO/NO- donors and as effective systems for investigation of metal-mediated crosstalk of known signaling agents.
dc.languageeng
dc.publisheruga
dc.rightsOn Campus Only Until 2018-08-01
dc.subjectNitroxyl
dc.subjectNitroxyl donor
dc.subjectCobalt
dc.subjectNitric Oxide
dc.subjectMetal nitrosyl
dc.titleSynthesis, structure, and reactivity of {CoNO}8/9 systems
dc.title.alternativedevelopment of cobalt-based nitroxyl donors and understanding the fate of Co-NO
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentChemistry
dc.description.majorChemistry
dc.description.advisorTodd C. Harrop
dc.description.committeeTodd C. Harrop
dc.description.committeeJeffrey L. Urbauer
dc.description.committeeMichael K. Johnson


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