Delivery of CO by bio-inspired metallocentres

Wright, Mark (2016) Delivery of CO by bio-inspired metallocentres. Doctoral thesis, University of East Anglia.

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Abstract

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.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Chemistry
Depositing User:	Users 4971 not found.
Date Deposited:	17 May 2017 14:13
Last Modified:	17 May 2017 14:13
URI:	https://ueaeprints.uea.ac.uk/id/eprint/63544
DOI:

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