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dc.contributor.advisorButler, Anthony (Anthony R.)en
dc.contributor.authorHarrison, Adrianne Calsyen
dc.coverage.spatial[ca 350] p.en
dc.description.abstractThe work described in this thesis represents an attempt to understand further the mode of action and metabolism of the hypotensive agent sodium nitroprusside (Na²[Feᴵᴵ(CN)₅NO]). The nitrosyl and cyanide ligands have been implicated in, respectively, the activity and toxicity of sodium nitroprusside and a brief review of the relevant literature is given in Chapter 1. Investigations of some in vitro reactions of the nitroprusside ion (NP), to better assess its in vivo reactions, are reported with particular interest in the integrity of the pentacyanoferrate moiety and reactions that result in nitrosation or release of NO. Most carbanions react with NP to form an oxime (Chapter 3), with the exceptions of the carbanions of pentane-2,4-dione and 3-methylpentane-2,4-dione for which an unusual mechanism involving metal to ligand charge transfer is proposed (Chapter 4). Consideration of the nmr spectra of some carbanions and oximes (Chapter 2) and the reactions of iron(II) with oximes (Chapter 3) contributes to the elucidation of this mechanism. A mechanism for the reactions of NP with a wide range of thiols, involving reduction of NP and slow release of NO, is proposed in Chapter 6. Although the primary product of NP reduction is [Fe(CN)₄NO]⁻ there has been no evidence of unbound cyanide, attributed to rapid ligand rearrangement yielding hexacyanoferrate(II). The same mechanism is consistent with the reactions of NP with the active site thiols of the enzymes papain and glyceraldehyde-3-phosphate dehydrogenase and the intracellular thiol glutathione of intact erythrocytes (Chapter 7). There is evidence (Chapter 8) of rapid reduction of NP and NO release upon reaction with the haem-containing enzymes catalase and lactoperoxidase, models for the enzyme guanylate cyclase through which NP and related agents are thought to effect hypotension.en
dc.publisherUniversity of St Andrewsen
dc.titleA study of reactions of the nitroprusside ion with some functional groups of clinical significanceen
dc.type.qualificationnamePhD Doctor of Philosopyen
dc.publisher.institutionThe University of St Andrewsen

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