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ESI mass spectrometry was used to assess the ability of metal complexes to inhibit binding of a transcription factor to a DNA molecule containing its recognition sequence. [ABSTRACT FROM AUTHOR]

Electrospray ionisation mass spectrometry, absorption spectrophotometry and circular dichroism spectroscopy were used to investigate the binding of a series of nickel complexes with the general formula [Ni(phen)2L]2+ (L = phen, dpq, dpqC and dppz) to a double stranded DNA hexadecamer. In addition, the binding of the complexes to pUC9 negatively supercoiled plasmid DNA was examined using gel electrophoresis, and their ability to inhibit DNA transcription was measured. Each of the above techniques showed that DNA binding strengthened as the size of the unique ligand L was increased. Comparison of the above results with those obtained previously, and presented here for the first time for the analogous series of ruthenium complexes [Ru(phen)2L]2+, showed that changing the metal ion from nickel to ruthenium consistently resulted in significant increases in DNA binding affinity.

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.