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Title: Delivery of CO by bio-inspired metallocentres
Author: Wright, Mark
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2016
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Although once thought to have no beneficial medicinal value due to its historic reputation as being a ‘silent killer’, recent investigations into the therapeutic applications of carbon monoxide (CO) on mammalian physiology have sparked a growing interest in designing metal-based carbonyl complexes to act as pro-drugs. Thoughtful design of transition metal carbonyl complexes result in controllable and tunable CO release triggered by photochemical labilization from the metal centre. The work contained in this thesis focuses on the design, synthesis and CO release capabilities of a series of photoactive ironbased carbon monoxide releasing molecules (photoCORMs). This work is complimented with studies of analogous ruthenium complexes. PhotoCORMs are able to impart spatial and temporal control over CO delivery following site specific irradiation with an appropriate wavelength. High energy ultra-violet light has poor tissue penetration and causes damage to the skin. Here, a series of iron carbonyl complexes were synthesised. Extension of the ligand conjugation system and addition of a nitrogen donor group proved to shift the absorption spectrum in a bathochromic fashion. Examination of photoCORM capabilities reveal the iron carbonyl complexes release CO following visible light irradiation. The number of developed CORMs which satisfy the required pharmaceutical characteristics is relatively small. Essential characteristics include water solubility and biocompatibility. We expand on the design of our complexes by incorporating thiolated saccharide ligands into the coordination sphere. The resulting dimeric carbonyl complexes display significantly enhanced water solubility as well as a major change in CO release behaviour. The anti-inflammatory properties of the photoCORM systems were investigated in vitro. Production of LPS-induced pro-inflammatory cytokine, TNF-a was markedly decreased following CORM administration. Surprisingly, CORM potency was greatest when cells were kept in the dark. Designing two photon up-converter systems is a leading strategy to enhanced the light harvesting ability of metal complexes. Here, the design of such attachable systems is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available