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

H 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).