Proligands and their Re(I) and Ir(III) Complexes for Imaging and Therapeutic Applications

Rhenium(I) and iridium(III) complexes present attractive alternatives to traditional organic fluorophores used in biological imaging due to their preferable photophysical properties and biological compatibility and stability. However, these complexes can also be designed to be biologically active, making them ideal for use in theranostics. This thesis describes the synthesis of a number of Re(I) and Ir(III) complexes containing substituted pyridyl 1,2,3-triazole ligands, their photophysical properties and early exploration into manipulation of these complexes for biological activity.

Cationic Re(I) complexes with electron withdrawing groups (EWGs) installed on the pyridyl-1,2,3-triazole ligands were synthesised with the aim of red-shifting the excitation profile into a more ideal range for confocal microscopy. The most successful of these was a nitrile substitution at the 4- position of the pyridyl ring, with ex = 366 nm and em = 596 nm; a 100 nm shift compared to the parent unsubstituted complex. Ir(III) complexes were also synthesised with the same EWGs on the pyridyl triazole ligands. Although a significant red shift was not achieved here, substitution with an amine gave rise to a lifetime of 441 ns and quantum yield of 18%, whilst substitution with an aldehyde presented a lifetime of 416 ns and quantum yield of 16%.

Initial investigations into modification of these complexes presented a ‘switch-on/off’ luminescence for complexes in which the aldehyde was converted into an imine. The recovery of this luminescence on imine hydrolysis points to potential for use as biological probes in acidic environments such as cancer cells. A change in the photophysical profile of the Re(I) ethyl ester complex upon ester hydrolysis shows promise as a synthetic handle for coupling biologically relevant molecules and pH sensitivity. Finally, early results show that a pyridyl-triazole ligand with a 4-carboxylate substitution of the pyridyl ring presents inhibition of histone demethylase enzymes (KDM7A/B).