Binding of the Δ- and Ʌ-enantiomers of [Ru(dmphen)(2)dpq](2+) to the hexanucleotide d(GTCGAC)(2)

1H NMR spectroscopy and viscosity measurements have been used to study the oligonucleotide binding of the Δ- and Ʌ-enantiomers of the metal complex [Ru(dmphen)2dpq]2+ (dmphen = 2,9-dimethyl-1,10-phenanthroline and dpq = dipyrido[3,2-f:2',3'-h]quinoxaline). The addition of either enantiomer to d(GTCGAC)2 induced large upfield shifts and significant broadening for the hexanucleotide imino and metal complex dpq resonances. These data coupled with the observed increase in the melting transition midpoint of the hexanucleotide duplex upon addition of either enantiomer suggests that both Δ- and Ʌ-[Ru(dmphen)2dpq]2+ bind by intercalation. A significant number of metal complex to hexanucleotide NOE contacts were observed in NOESY spectra of d(GTCGAC)2 with added Δ- or Ʌ-[Ru(dmphen)2dpq]2+. The observed intermolecular NOEs were consistent with both enantiomers intercalating between the G4A5 bases of one strand and the T2C3 bases of the complementary strand. Intermolecular NOEs from the dmphen protons were only observed to protons located in the hexanucleotide minor groove. Alternatively, NOE contacts from the dpq protons were observed to both major and minor groove protons. The NOE data suggest that the dpq ligand of the Δ-enantiomer intercalates deeply into the hexanucleotide base stack while the Ʌ-enantiomer can only partially intercalate. Viscosity measurements were consistent with the proposed intercalation binding models. The addition of the Δ-enantiomer increased the relative viscosity of the DNA solution, while a decrease in the relative viscosity of the DNA was observed upon addition of the Ʌ-metal complex. These results confirm our proposal that octahedral metallointercalators can intercalate from the minor groove. In addition, the results demonstrate that the left-handed enantiomer of [Ru(dmphen)2dpq]2+ prefers to intercalate from the narrow minor groove despite only being able to partially insert a polycyclic aromatic ligand into the DNA base stack.