Synthesis of fluorescent phosphorus ligands and their applications in medical imaging and catalysis

Abstract

This thesis reports the synthesis of novel, air-stable, fluorescent phosphorus-containing compounds, based on a Bodipy backbone, and their applications in cell imaging and catalysis. The syntheses of all the novel target compounds reported in this thesis are via a primary phosphine, an under-utilised class of compound due to a hazardous reputation. Chapter 1 explores the stability of primary phosphines, how they can be made user-friendly and the ability to create a library of novel phosphorus compounds via the phosphorus-hydrogen bonds. The LJH group synthesised the first, air-stable, fluorescent primary phosphine and Chapter 2 explores a second generation of this type of ligand with an increased fluorescent quantum yield due to the addition of alkyne groups on the boron atom. Chapter 3 details the coordination chemistry of primary phosphines to group 6 and 8 transition metals. Interestingly, the addition of the metals had different effects on the photophysical properties, group 6 metal complexes retained high quantum yields, whereas group 8 metals quenched the fluorescence, possibly due to the heavy atom effect. Chapter 4 discusses the synthesis of fluorescent phosphonium salts which have the potential to be used as trifunctional imaging agents. The three functions within the compounds include i) a fluorophore, to provide in vitro fluorescence imaging, ii) a positive charge on the phosphorus atom to introduce organelle specificity – in this case, to the mitochondria and iii) the inclusion of an 18F radioisotope enables in vivo imaging techniques such as PET imaging. Chapter 5 shows further versatility of fluorescent primary phosphines where we report the synthesis of a novel, chiral, fluorescent phosphonite ligand that has been tested for its applications as a catalyst in asymmetric hydrogenation reactions of a benchmark substrate. The results showed full conversion and an enantiomeric excess (ee) of >99%. The final chapter discusses the importance of the aryl linker between the Bodipy core and the phosphorus atom. The compounds synthesised in this chapter show decreased fluorescence when the phosphorus atom is directly bound to the fluorophore and have potential applications as a switch.