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Title: Biophysical studies on a novel family of iridium polypyridyl complexes
Author: Stimpson, Sasha
ISNI:       0000 0004 7960 341X
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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This thesis describes the synthesis of three new iridium polypyridyl complexes; [Ir(bpy)2(dppz)]3+ 1, [Ir(phen)2(dppz)]3+ 2, [Ir(phen)2(C^N dppz)]2+ 3 (where bpy = 2,2' bypyridine, phen = 1,10-phenanthroline, dppz = dipyrido[3:2- a:2',3'-c]phenazine). This group of structurally related complexes vary in steric and charge properties. Photophysical studies show that the complexes are all emissive with long-lived luminesce lifetimes of ~500 ns and above. Biophysical studies with the three iridium complexes and CT-DNA were carried out. Viscometry measurements indicate that the dppz derivatives clearly intercalate between DNA base pairs. Spectroscopic techniques show all three complexes bind to DNA with high affinities ~ 106 M-1 - values similar to their ruthenium-dppz analogues. DNA "light-switch" behaviour is not observed upon interaction with nucleic acids, in fact, a substantial decrease in steady-state luminescence occurs in the presence of CT-DNA. Follow up titrations with guanosine-5'-monophosphate shows redox quenching. The photonuclease activity of these complexes were investigated using supercoiled plasmid DNA, with complexes 1 and 2 producing scissions in the supercoiled structure. Transient absorption spectroscopy was used to monitor the intramolecular excited state processes. The excited state kinetics of the complexes in the presence of DNA were quite different to that of the free complex in solution, suggesting that there is an electron transfer reaction between the complexes and the guanine bases. The later part of this thesis investigated the cellular uptake of the complexes 1-3. Confocal laser scanning microscopy of the complexes showed that they were internalised by the MCF-7 breast cancer cell line. Further colocalisation studies showed specific organelle targeting, with 1 and 3 imaging lysosomes, and 2 imaging mitochondria. Cell viability studies on 2 alongside the highly potent cisplatin showed no/low cytotoxic activity in the dark. However, upon photo-irradiation the complex became more cytotoxic. Inductively coupled mass spectrometry showed that the complex displayed increased cellular uptake in serum free conditions. This work has established novel iridium complexes, reported DNA binding interactions and preliminary cellular studies.
Supervisor: Thomas, James Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available