A comparison of the binding of metal complexes to duplex and quadruplex DNA

Abstract

Electrospray ionisation mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy were used to compare the binding of mononuclear nickel, ruthenium and platinum complexes to double stranded DNA (dsDNA) and quadruplex DNA (qDNA). CD studies provided evidence for the binding of intact complexes of all three metal ions to qDNA. ESI mass spectra of solutions containing platinum or ruthenium complexes and qDNA showed evidence for the formation of non-covalent complexes consisting of intact metal molecules bound to DNA. However, the corresponding spectra of solutions containing nickel complexes principally contained ions consisting of fragments of the initial nickel molecule bound to qDNA. In contrast ESI mass spectra of solutions containing nickel, ruthenium or platinum complexes and dsDNA only showed the presence of ions attributable to intact metal molecules bound to DNA. The fragmentation observed in mass spectral studies of solutions containing nickel complexes and qDNA is attributable to the lower thermodynamic stability of the former metal complexes relative to those containing platinum or ruthenium, as well as the slightly harsher instrumental conditions required to obtain spectra of qDNA. This conclusion is supported by the results of tandem mass spectral studies, which showed that ions consisting of intact nickel complexes bound to qDNA readily undergo fragmentation by loss of one of the ligands initially bound to the metal. The ESI-MS results also demonstrate that the binding affinity of each of the platinum and ruthenium complexes towards qDNA is significantly less than that towards dsDNA.

Crystal structure, DNA binding studies, nucleolytic property and topoisomerase I inhibition of zinc complex with 1,10-phenanthroline and 3-methyl-picolinic acid

“…and [Ru(phen) 3 ] 2? , with four stranded G-quadruplex (TTGGGGGT) 4 shows significant decrease in ellipticity of both CD positive and negative bands with increasing Ru(II)-complex: G-quadruplex ratio (Talib et al 2008). The positive CD band at 265 nm was found to be split into two distinct bands at higher concentration of Ru(II)-complex.…”

Studies on synthesis, characterization, and G-quadruplex binding of Ru(II) complexes containing two dppz ligands

“…These complexes generally have positively charged substituents, which can interact with the grooves of the quadruplex, and a positively charged center, which can stay near the center of the guanine quartet. The metal plays a major structural role in organizing the ligand(s) into an optimal structure for quadruplex DNA interaction [16][17][18][19]. Also, the electropositive metal is in principle positioned at the center of the guanine quartet and increases electrostatic stabilization by substituting the cationic charge of the potassium or sodium that normally occupies this site.…”

Design, synthesis and evaluation of 4,7-diamino-1,10-phenanthroline G-quadruplex ligands

“…[31][32][33] A common feature observed for most of the compounds is the 2,9-substitutional pattern around the central phenanthroline scaffold. The only 4,7-disubstituted 1,10-phenanthroline evaluated as G-quadruplex ligand is MOP1, 27,28 which showed very limited G-quadruplex stabilizing abilities in a FRET quadruplex melting assay despite four positive charges.…”