Synthesis, characterisation, DNA binding interactions, and biological activity of nickel Schiff base complexes

A series of fourteen new nickel Schiff base complexes was synthesised by a two-step procedure. Initially 2,4,6-trihydroxybenzaldehyde was reacted with 1-(2-chloroethyl)piperidine hydrochloride, 4-(2-chloroethyl)morpholine hydrochloride or 1-(3-chloropropyl)piperidine hydrochloride in the presence of K2CO3 to afford three organic precursor compounds featuring different pendant groups. These compounds were then successfully reacted with different diamines in the presence of Ni(II) to form a series of nickel Schiff base complexes featuring four pendant groups. All new organic compounds and nickel complexes were characterised using 1D and 2D nuclear magnetic resonance (NMR) spectroscopic methods, elemental microanalysis and electrospray ionisation mass spectrometry (ESI-MS). The solid-state structures of four nickel complexes were determined by single crystal X-ray crystallography and revealed that the coordination geometry around the nickel ion was square planar in each case. The ability of the nickel complexes to bind to the double stranded DNA molecule D2, the tetramolecular G-quadruplex Q4, the unimolecular G-quadruplex Q1 in its parallel, anti-parallel and hybrid topologies, the parallel unimolecular G-quadruplex c-KIT1, and the fluorescently labelled unimolecular G-quadruplex F21T, was investigated using ESI-MS and circular dichroism (CD) spectroscopy, Fluorescence Indicator Displacement (FID) assays, Fluorescence Resonance Energy Transfer (FRET) melting assays and molecular docking

DNA-binding interactions of nickel Schiff base complexes

A series of eleven different nickel Schiff base complexes was synthesized by a two-step procedure. Initially ethylenediamine, phenylenediamine or meso- 1,2-diphenylethylenediamine was reacted with either 2,3- or 2,5- dihydroxybenzaldehyde in the presence of Ni(II) to afford six novel dihydroxylated nickel Schiff base complexes. Five of these complexes were then successfully reacted with 1-(2-chloroethyl) piperidine hydrochloride to form a series of derivatives featuring two appended ethyl piperidine moieties. All new complexes were characterised using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, elemental microanalysis and in some instances electrospray ionisation mass spectrometry (ESI-MS). The solidstate structures of three nickel complexes (5), (8) and (10) were determined by single crystal X-ray crystallography, and revealed that the coordination geometry around the nickel ion was square planar in each case. The ability of the nickel complexes containing appended ethyl piperidine groups to bind to a double-stranded 16mer DNA molecule, and a tetramolecular DNA quadruplex, was investigated using ESI-MS and circular dichroism (CD) spectroscopy. The results of these studies, as well as those performed simultaneously using a series of previously reported analogues prepared by the same synthetic pathway, but with 2,4- dihydroxybenzaldehyde as one of the initial reactants, enabled the effect of varying the position of the ethyl piperidine groups on DNA-binding properties to be explored. Generally, it was found that changing the position of the ethyl piperidine groups had only a small effect on binding affinity towards either type of DNA molecule. In most cases there was good agreement between orders of relative binding affinity towards a given DNA molecule determined using the two spectroscopic techniques. On some occasions, however, the results of binding studies conducted using ESI-MS and CD spectroscopy diverged significantly. This may have been the result of the two methods showing different sensitivities towards different aspects of the metal complex/DNA interaction, and the varying stabilities of the non-covalent complexes formed in these systems, to the gas phase environment of the ESI mass spectrometer or to the solution phase used in CD experiments