Carbon monoxide sensing in biological environments
File(s)
Author(s)
Robson, Jonathan Alexander
Type
Thesis
Abstract
Chapter 1 reviews the literature surrounding gaseous small molecules and their sensors in biological environments. In particular, the biological relevance of CO is described, focusing on its production in the cell and role as a small signalling molecule. Development of carbon monoxide (CO) sensors has previously been limited to air and solution studies, however, the latest literature which highlights potential sensing applications in vitro and in vivo has been reviewed.
Chapter 2 demonstrates a successful method to detect CO produced by both exogenous and stimulated endogenous methods in vitro. The detection method is based on the heavy atom effect, in which a BODIPY fluorophore is quenched due to attachment to a metal centre, but in the presence of CO the fluorophore is instantaneously released, and the fluorescence signal is restored.
Chapter 3 describes a second method to detect CO, this detection method relies upon a change of electronic properties around a metal centre. The binding of CO reduces the non-radiative decay pathways promoted in the vinyl fluorophore metal complex. These probes were able to achieve large increases in fluorescence upon CO binding and in vitro studies were expanded to detect endogenous CO for the first time.
Chapter 4 highlights how the probes developed in previous chapters can be made more suitable for in vivo studies. In particular the development of longer wavelength probes with greater tissue penetration is described in detail. The possibility of coupling near-IR probes with targeting units was also explored.
Chapter 6 provides experimental details and characterisation for fluorophores and probes developed and described in previous chapters.
Chapter 2 demonstrates a successful method to detect CO produced by both exogenous and stimulated endogenous methods in vitro. The detection method is based on the heavy atom effect, in which a BODIPY fluorophore is quenched due to attachment to a metal centre, but in the presence of CO the fluorophore is instantaneously released, and the fluorescence signal is restored.
Chapter 3 describes a second method to detect CO, this detection method relies upon a change of electronic properties around a metal centre. The binding of CO reduces the non-radiative decay pathways promoted in the vinyl fluorophore metal complex. These probes were able to achieve large increases in fluorescence upon CO binding and in vitro studies were expanded to detect endogenous CO for the first time.
Chapter 4 highlights how the probes developed in previous chapters can be made more suitable for in vivo studies. In particular the development of longer wavelength probes with greater tissue penetration is described in detail. The possibility of coupling near-IR probes with targeting units was also explored.
Chapter 6 provides experimental details and characterisation for fluorophores and probes developed and described in previous chapters.
Version
Open Access
Date Issued
2018-11
Date Awarded
2019-02
Copyright Statement
Creative Commons Attribution NonCommercial Licence
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)