Mono- and bi-metallic ru(ii) probes for the detection of carbon monoxide in biological environments.
File(s)
Author(s)
Hendley, Rian
Type
Thesis
Abstract
Endogenously produced CO preconditions cells to survive periods of oxidative stress through an array of different roles it plays in the cell. To gain a further understanding of these effects, sensitive and selective probes are needed for the detection of endogenous CO. The majority of reported probes for the detection of CO in cells rely on (often) ill-defined palladium-mediated reactions with CO to produce a turn-on signal. These probes tend to have incubation times of tens of minutes before any significant signal is produced, leading to a lack of real-time information. Previous work in the Wilton-Ely group has shown that Ru(II) complexes display high sensitivity and selectivity towards CO, as well as only taking seconds to produce a detectable signal. Utilising the versatility of the previously reported Ru(II) system, a range of cellular CO probes has been synthesised bearing different fluorophores and targeting groups. It was found that using bimetallic Ru(II) probes instead of monometallic probes significantly increases the overall fluorescence turn-on response towards CO. However, both the mono- and bimetallic probes still showed good to excellent selectivity and sensitivity towards CO, and none showed any effect on cell viability at concentrations well above those used for imaging studies. Modifying the core of the BODIPY fluorophore through extended conjugated units allowed a bimetallic probe to be prepared that operates in the biological imaging window above 700 nm. These promising results showed that the probes are feasible for the detection of endogenously produced CO, and a selection of the best-performing probes was carried forward into cellular imaging studies. Cellular imaging studies showed that a probe containing lipophilic cations localizes as expected in the mitochondria and that this probe can detect endogenously produced CO...
Version
Open Access
Date Issued
2023-01-10
Date Awarded
01/04/2023
License URL
Advisor
Wilton-Ely, James
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)