A ¹H NMR Study of the DNA Binding of Ruthenium(II) Polypyridyl Complexes

Abstract

1H NMR spectroscopy was used to study the oligonucleotide binding of the Δ enantiomers of [Ru(phen)2L]2+ where the bidentate ligand L is 1,10-phenanthroline (phen), dipyrido[3,2-d:2‘,3‘-f]quinoxaline (dpq) or dipyrido[3,2-a:2‘,3‘-c](6,7,8,9-tetrahydro)phenazine (dpqC). The data from one- and two-dimensional NMR experiments of the oligonucleotide−metal complex binding suggest that all three ruthenium(II) polypyridyl complexes bind in the DNA minor groove. While a minimally intercalated oligonucleotide binding mode may be proposed for Δ-[Ru(phen)3]2+, the NMR data clearly indicate that Δ-[Ru(phen)2dpq]2+ binds the hexanucleotide d(GTCGAC)2 by intercalation, of the dpq ligand, from the minor groove. This demonstrates that metallointercalators can intercalate from the DNA minor groove. Molecular modeling of the metal complex in the intercalation site suggests that Δ-[Ru(phen)2dpq]2+ binds in a “head-on” fashion with the phenanthroline rings in the minor groove and the dpq ligand inserted into the nucleotide base stack. NOESY experiments of the binding of Δ-[Ru(phen)2dpq]2+ with d(GTCGAC)2 and d(TCGGGATCCCGA)2 suggest that intercalation from the minor groove is favored at purine−purine/pyrimidine−pyrimidine sequences for this complex. The syntheses of Δ-[Ru(phen)2dpq]2+ and Δ-[Ru(phen)2dpqC]2+ are reported along with crystal structure of [Ru(phen)2dpq](PF6)2 (monoclinic crystal system, space group P21 /c, Z = 4, a = 9.483(2) Å, b = 33.374(6) Å, c = 12.900(3) Å, β = 110.05(2)°, V = 3835(2) Å3).

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

“…The ligand dipyrido-[3,2-d:2 0 ,3 0 -f]-quinoxaline was synthesized by Hambly et al [34]. Ultrapure Milli Q water (18.3 lX) was used for all experiments.…”

Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

“…When ESI mass spectra were acquired in positive ion mode (Figures 6a and b), there were no significant ions present from any dsDNAdrug complex in any of the mixtures; the only ions observed were from free D3 or single strands from D3. In contrast, the negative ion spectra (Figures 6c and d) showed ions from dsDNA-drug complexes with the number of drug molecules bound to DNA increasing with increasing amounts of [Ru(phen) 2 Since DNA is negatively charged in solution and these Ru-based compounds have been shown to bind to DNA using other techniques [23], the negative ion spectra are likely to provide a more accurate picture of the complexes present in solution. Furthermore, previously it has been shown that complexes of well-characterized intercalators with dsDNA can be detected in positive and negative ion ESI mass spectra [6,14].…”

“…NMR studies show that these ligands intercalate between DNA base pairs [23]. In the present work, we have focused on the interactions of [Ru(phen) 2 dpq]Cl 2 and [Ru(phen) 2 dpqC]Cl 2 with D3.…”

“…Two relatively GC-rich DNA strands (D1 and D3) were also used, which were therefore not predicted to favor the minor groove-binding mode of interaction with dsDNA. The extended aromatic ring systems of [Ru(phen) 2 dpq]Cl 2 and [Ru(phen) 2 dpqC]Cl 2 intercalate between DNA base pairs, and were expected to bind to these sequences [23]. The data presented suggest that different binding modes may be differentially favored in positive and negative ion ESI mass spectra.…”

Mechanisms of DNA binding determined in optical tweezers experiments

“…The basic structures consist of a Ru(II) surrounded by three heterocyclic, aromatic ligands. [84][85][86] Specific structures include Ru(phen) 3 2+ and Ru(bpy) 2 dppz 2+ . Recent AFM studies have determined the binding constant of Ru(bpy) 2 dppz 2+ to be (1.5 6 0.7) Â 10 5 M À1,28 by examining the length of the DNA as a function of ligand concentration.…”