Studies on the reactivity of copper complexes with NO and CO, and their applications in molecular imaging
Author(s)
Wilson, Neil
Type
Thesis
Abstract
This thesis is concerned with the development of metal complexes capable of selectively
trapping and releasing nitric oxide and carbon monoxide. In the case of the former, we have
utilised copper(II) complexes containing a nitrobenzofurazan (NBD) fluorophore which exhibit a
restoration of fluorescence in the presence of nitric oxide. These complexes have shown to be
water soluble, cell permeable, non toxic and selective towards nitric oxide over several other
reactive oxygen and nitrogen species of biological relevance. For this reason these complexes
have been used for the cellular imaging of nitric oxide. We have shown that our complexes can
be localised within the cell membrane and can be used to image NO with a detection limit of
1μM.
The second part of this thesis deals with the synthesis of copper(I) complexes of tris(2-
pyridylmethyl)amine (tmpa) and their reactivity towards carbon monoxide. The aim of these
studies was to develop pre-concentrating reagents capable of trapping 11CO for radiolabelling
applications (more specifically for Positron Emission Tomography (PET) labelling). Indeed,
these copper(I) complexes have been shown to trap near quantitative amounts of 11CO from
nitrogen-rich gas streams without the need for elevated pressure or low temperature. To be
useful, the trapping/release system must be compatible with some means of incorporating the CO
into the desired target molecule. It has been demonstrated that [Cu(tmpa)(CO)]+ can be used as
the CO source when performing palladium-catalysed carbonylations between amines and aryl
halides to form amides.
trapping and releasing nitric oxide and carbon monoxide. In the case of the former, we have
utilised copper(II) complexes containing a nitrobenzofurazan (NBD) fluorophore which exhibit a
restoration of fluorescence in the presence of nitric oxide. These complexes have shown to be
water soluble, cell permeable, non toxic and selective towards nitric oxide over several other
reactive oxygen and nitrogen species of biological relevance. For this reason these complexes
have been used for the cellular imaging of nitric oxide. We have shown that our complexes can
be localised within the cell membrane and can be used to image NO with a detection limit of
1μM.
The second part of this thesis deals with the synthesis of copper(I) complexes of tris(2-
pyridylmethyl)amine (tmpa) and their reactivity towards carbon monoxide. The aim of these
studies was to develop pre-concentrating reagents capable of trapping 11CO for radiolabelling
applications (more specifically for Positron Emission Tomography (PET) labelling). Indeed,
these copper(I) complexes have been shown to trap near quantitative amounts of 11CO from
nitrogen-rich gas streams without the need for elevated pressure or low temperature. To be
useful, the trapping/release system must be compatible with some means of incorporating the CO
into the desired target molecule. It has been demonstrated that [Cu(tmpa)(CO)]+ can be used as
the CO source when performing palladium-catalysed carbonylations between amines and aryl
halides to form amides.
Date Issued
2011-09
Date Awarded
2012-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Long, Nicholas
Woscholski, Rudiger
Vilar, Ramon
Sponsor
GSK and EPSRC
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)