Year

2019

Degree Name

Doctor of Philosophy

Department

School of Chemistry and Molecular Bioscience

Abstract

Thirteen novel Schiff base complexes have been successfully synthesised through reactions of substituted benzophenones with different diamines in the presence of nickel(II) acetate. These precursor complexes then were successfully alkylated using 1-(2-choroethyl)piperidine hydrochloride to form a series of novel nickel complexes bearing dimethylenepiperidine pendant groups. The nickel complexes with the pendant groups were sufficiently soluble in water to enable them to be used in DNA binding experiments. All new complexes were fully characterised using NMR spectroscopy, Electrospray Ionisation Mass Spectrometry (ESI-MS) and elemental microanalysis. In addition, the solid state structures of eight complexes were determined using X-ray crystallography.

Various techniques including ESI-MS, Circular Dichroism (CD), UV-Vis spectrophotometry, Fluorescence Indicator Displacement (FID), Fluorescence Resonance Energy Transfer (FRET) melting assays and molecular docking were employed to investigate the effects of structural variations amongst the nickel Schiff base complexes on their DNA binding properties. DNA binding studies were performed using the tetramolecular G-quadruplex Q4, the unimolecular G-quadruplexes Q1 and c-kit1, the fluorescently labelled unimolecular G-quadruplex F21T, and the double stranded DNA molecule D2. Experiments involving Q1 were performed after it was annealed under specific conditions to afford parallel, antiparallel and hybrid topologies. The results of DNA binding studies indicated that varying the number of pendant groups appended to the Schiff base scaffold resulted in the largest changes to DNA affinity and selectivity. For example, complex (89), carrying four pendant groups exhibited strong affinities towards many kinds of G- quadruplex DNA, including parallel Q4 and Q1, anti-parallel Q1, c-kit1 and antiparallel F21T.

DNA binding studies performed using five isomeric nickel Schiff base complexes containing two pendant groups in different locations also showed significant variations in the strength of interactions with some G-quadruplexes, such as parallel Q4, parallel c-kit1, and anti-parallel F21T. Modifying the diamine moieties in the top half of the nickel Schiff base complexes, and introducing asymmetry into their structures, resulted generally in smaller changes to DNA affinities and selectivities.

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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.