Oxidative stress is implicated in the ageing process and age-related diseases. A dual sensor spin trap i was used with electron paramagnetic resonance (EPR) spectroscopy to detect and distinguish between oxygen-centred radicals, carbon centred radicals and redox active metal ions, all of which contribute to oxidative stress. A novel mitochondria-targeted nitrone spin trap MitoSpin vi has been prepared for the detection and amelioration of oxidative stress. The synthesis utilises a novel Parham-type cyclization of aryl bromide iv to afford the isoindolone core vI in good yield. MitoSpin vi accumulates in mitochondria in the presence of a membrane potential and affords a unique EPR signal and electrospray ionisation mass spectrometry (ESI-MS) detectable oxidation product on reaction with hydroxyl radicals. A hydrogen peroxide-sensitive, mitochondria-targeted probe vii has been prepared. It utilises the reactivity of the boronate moiety with hydrogen peroxide to afford an oxidation product. This process is easy to detect by ESI-MS. Mitochondrial moderators were synthesised, which are designed to react with to release an uncoupler (proton trans locator). If released in vivo the uncoupler would lower the mitochondrial membrane potential inhibiting further ROS production.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:566433 |
| Date | January 2010 |
| Creators | Quin, Caroline |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/1576/ |
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