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

1 H NMR spectroscopy was used to study the oligonucleotide binding of the Δ enantiomers of [Ru(phen) 2 L] 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) 2 dpq] 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) 2 dpq] 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) 2 dpq] 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) 2 dpq] 2+ and Δ-[Ru(phen) 2 dpqC] 2+ are reported along with crystal structure of [Ru(phen) 2 dpq](PF 6 ) 2 (monoclinic crystal system, space group P 2 1 /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) Å 3 ).