Meso-[{Ru(phen)2}2(μ-bpm)]4+: A high-affinity DNA bulge probe {bpm = 2,2′-bipyrimidine; phen = 1,10-phenanthroline}

The binding of the stereoisomers of [{Ru(Me2bpy)2}2(μ-bpm)]4+, [{Ru(phen)2}2(μ-bpm)]4+ and [{Ru(Me2phen)2}2(μ-bpm)]4+ (Me2bpy = 4,4′-dimethyl-2,2′-bipyridine; bpm = 2,2′-bipyrimidine; phen = 1,10-phenanthroline; Me2phen = 4,7-dimethyl-1,10-phenanthroline) to a tridecanucleotide d(CCGAGAATTCCGG)2 which contains a single adenine bulge site, and four control dodecanucleotides, have been studied using a fluorescence intercalator displacement (FID) assay. The meso isomer of [{Ru(phen)2}2(μ-bpm)]4+ showed the strongest binding to the bulge-containing tridecanucleotide. In order to gain a greater understanding of the basis of the higher affinity exhibited by the meso isomer towards the bulge sequence, a 1H NMR study of the binding of the two enantiomers (ΔΔ and ΛΛ) of rac-[{Ru(phen)2}2(μ-bpm)]4+, and the, meso (ΔΛ) diastereoisomer, to the tridecanucleotide d(CCGAGAATTCCGG)2 was carried out. The NMR results suggest that the meso isomer binds selectively at the bulge site in the tridecanucleotide minor groove, but closer to the 3′-direction and with less structural perturbations of the groove than the ΔΔ and ΛΛ isomers. The results of this study confirm that dinuclear ruthenium complexes have excellent potential as DNA bulge probes, and meso-[{Ru(phen)2}2(μ-bpm)]4+ in particular has a high affinity (1 × 106 M−1) and selectivity for a single adenine bulge site.

Graphical abstractThe binding of stereoisomers of a range of dinuclear ruthenium complexes to DNA is reported. Meso-[{Ru(phen)2}2(μ-bpm)]4+: (bpm = 2,2′-bipyrimidine; phen = 1,10-phenanthroline) showed particularly strong affinity and selectivity for a bulge site in the target oligonucleotide. A 1H NMR study of the binding by this species and its stereoisomers has been undertaken.Figure optionsDownload full-size imageDownload as PowerPoint slide