Synthesis and Studies on Novel Luminescent Ir(III) Complexes that Interact with Biomolecules

The syntheses of three novel iridium(III) polypyridyl complexes have been investigated as a potential route to obtain DNA imaging probes and diagnostic agents. The reported metal complexes are: [Ir(bpy)2(qtpy)]3+ 1, [Ir(phen)2(qtpy)]3+ 2, [Ir(dppz)2(qtpy)]3+ 3 (where bpy = 2,2’-bipyridine, phen = 1,10-phenanthroline, dppz = dipyrido[3:2- a:2’,3’-c]phenazine and qtpy = 2,2’:4,4’’:4’,4’’’-quaterpyridine). This library of isostructural complexes varies in steric and charge properties. Particular attention has been devoted to qtpy, as this was chosen as the bridging ligand. The qtpy ligand can bind to a metal centre through a bidentate diimine site and to two other metal centres through two monodentate imine sites. All the complexes were obtained through a microwave-assisted synthesis as conventional reflux heating proved abortive to afford the complexes. Single X-ray crystallography afforded the crystal structures of 15 precursors used in the synthesis of the eventual title complexes. Photophysical studies show that the complexes exhibit highly tunable emission, with their triplet state metal-to-ligand (3MLCT) charge-transfer bands extending up to ~500nm. Moreover, luminescence lifetimes measurements show that the three complexes possess long-lived average lifetimes of around ~4–5ns. Luminescent DNA-binding investigations demonstrate the complexes bind to DNA with binding affinities ~ 104M-1. Contrary to their ruthenium(II)-based analogues, DNA “light-switch” behaviour is not observed upon interaction with duplex DNA; instead, a massive luminescence attenuation occurs. The complexes also produce singlet oxygen to varying extents, up to 71%, as in the case of the dppz complex. The complexes equally binded non-canonical G-quadruplex DNA (human telomeric sequence), with luminescence quenching observed for both Complexes 1 and 2 and luminescence enhancement observed for Complex 3. Follow up titrations with guanosine-5’-monophosphate (5’-GMP) and adenosine 5’-monophosphate (5’-AMP) showed redox quenching, with consequent luminescence decrease observed in both cases, even though this was more pronounced in the case of 5’-GMP additions. The photocleavage activities of these complexes were investigated using supercoiled plasmid DNA, with Complex 1 (the representative complex selected) cleaving plasmid DNA by producing scissions in the supercoiled structure. The investigated compounds also have a protein target and in fact, are bound to both bovine serum albumin (BSA) and human serum albumin (HSA). The binding interactions were further evidenced by circular dichroism spectroscopic experiments. Molecular docking studies showed that the complexes are true Warfarin site (Sudlow Site I) binders. The concluding part of this thesis focuses on the cytotoxicity studies of the complexes. Research attention has been drawn to this area because metal complexes are significantly advantageous as luminescent DNA probes. Cell viability studies of the complexes towards human oral squamous cell carcinoma (H357) demonstrated no or low cytotoxic activity for Complexes 1 and 2, whereas Complex 3 is particularly selective and potent towards H357 cancer cells. The work described in this thesis has successfully established novel iridium complexes and reported their duplex and G-quadruplex DNA- and protein-binding interactions and preliminary cellular studies.