G-quadruplex DNA binding properties of novel nickel Schiff base complexes with four pendant groups

Abstract

Three new nickel Schiff base complexes were prepared using a two-step procedure that involves initial selective dialkylation of 2,4,6-trihydroxybenzaldehyde, followed by reaction with 1,2-phenylenediamine and nickel(II) acetate. Each of the complexes possessed the same Schiff base core but differed in the identity of the four pendant groups. All complexes were characterised by microanalysis, NMR spectroscopy and ESI mass spectrometry. In addition, two of the complexes were also characterised in the solid state using X-ray crystallography, which confirmed the presence of a square planar geometry around the metal ion. The DNA binding properties of the three nickel complexes with double stranded DNA and a range of G-quadruplex DNA structures were explored using ESI mass spectrometry, CD spectroscopy, UV melting curves, Fluorescence Resonance Energy Transfer (FRET) assays, Fluorescent Indicator Displacement (FID) assays and molecular docking studies. These techniques confirmed the ability of the three nickel complexes to bind to most of the DNA molecules examined, as well as stabilise the latter in several instances. In addition, the results of these investigations provided evidence that pendant groups with morpholine rings generally reduced DNA binding behaviour, whilst pendants featuring piperidine ring systems attached to the Schiff base core by three and not two methylene linkers often showed the greatest extent of binding or DNA stabilisation.