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

H-1 NMR spectroscopy and viscosity measurements have been used to study the oligonucleotide binding of the hand Lambda-enantiomers of the metal comple x [Ru(dmphen)(2)dpq](2+) (dmphen = 2,9-dimethyl-1,10-phenanthroline and dpq = dipyrido[3,2-f:2',3'-h]quinoxaline). The addition of either enantiomer t o d(GTCGAC)2 induced large upfield shifts and significant broadening for th e hexanucleotide imino and metal complex dpq resonances. These data coupled with the observed increase in the melting transition midpoint of the hexan ucleotide duplex upon addition of either enantiomer suggests that both Delt a- and Lambda-[Ru(dmphen)(2)dpq](2+) bind by intercalation. A significant n umber of metal complex to hexanucleotide NOE contacts were observed in NOES Y spectra of d(GTCGAC)(2) with added Delta- or Lambda-[Ru(dmphen)(2)dpq](2). The observed intermolecular NOEs were consistent with both enantiomers i ntercalating between the G(4)A(5) 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. Alter natively, 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 Delt a-enantiomer intercalates deeply into the hexanucleotide base stack while t he Lambda-enantiomer can only partially intercalate. Viscosity measurements were consistent with the proposed intercalation binding models. The additi on of the Delta-enantiomer increased the relative viscosity of the DNA solu tion, while a decrease in the relative viscosity of the DNA was observed up on addition of the Lambda-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)(2)dpq](2+) prefers to intercalate from the narrow minor groove d espite only being able to partially insert a polycyclic aromatic ligand int o the DNA base stack.