Studies on the reactivity of copper complexes with NO and CO, and their applications in molecular imaging

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.