Year

2015

Degree Name

Doctor of Philosophy

Department

School of Chemistry

Abstract

A range of structurally diverse novel nickel Schiff base complexes were synthesised, the synthetic procedures optimised and the resultant complexes fully characterised by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and in some instances electrospray ionisation mass spectrometry (ESI-MS) and X-ray crystallography. The binding of these complexes to both duplex DNA (dsDNA) and several different quadruplex DNA (qDNA) structures was then examined using a range of techniques, which included ESI-MS, circular dichroism (CD) spectroscopy, UV-Vis thermal melting profiles, fluorescence resonance energy transfer (FRET) melting and competition assays, and NMR spectroscopy. The DNA-binding behaviour of these novel complexes was then compared to that of some structurally related nickel Schiff base complexes previously reported in the literature.

The literature complexes (2) and (12), which contain a 1,2- phenylenediamine moiety, were found have a high affinity for both dsDNA and qDNA. In contrast, the novel complexes (6) and (13), both of which differ from (2) and (12) in having a meso-1,2-diphenylethylenediamine moiety instead of 1,2-phenylenediamine, were found to have little to no affinity for D2, yet were able to bind to all forms of qDNA, especially the tetramolecular Q4(5G) and Q4(4G). This result suggests that the presence of a non-planar ligand may engender selectivity for qDNA over dsDNA upon this class of metal complexes.

The effect of aromatic surface area upon DNA binding affinity was also examined. It was found that the presence of a large, planar 9,10- diaminophenanthrene unit in complex (4) improved affinity for dsDNA, but inhibited binding to several qDNA molecules. The positioning of additional fused aromatic rings within the nickel complexes was also found to be very important for DNA binding interactions. ESI-MS and CD studies involving the two asymmetric complexes (15) and (16), both of which contained a single naphthaldehyde moiety, exhibited little to no binding to dsDNA, as well as limited binding to qDNA. This result may also reflect the importance of electrostatic interactions in the overall binding of this class of molecules to DNA. This is due to the fact that (15) and (16) only contain one piperidine ring, and therefore exist as monoprotonated species in aqueous solution, as opposed to all the other complexes examined which would have been diprotonated under the same conditions.

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.