Minor groove intercalation of Delta-[Ru(Me(2)phen)(2)dppz](2+) to the hexanucleotide d(GTCGAC)(2)

The metal complex Delta-[Ru(Me(2)phen)(2)dppz](2+) (Me(2)phen = 2,9-dimethyl-1,10-phenanthroline; dppz = dipyrido-[3,2-a:2',3'-c]phenazine) has been synthesised and its binding to the hexanucleotide d(GTCGAC)(2) studied by H-1 NMR spectroscopy. The crystal structure of rac-[Ru(Me(2)phen)(2)dppz](PF6)(2).2H(2)O has been determined. Addition of Delta-[Ru(Me(2)phen)(2)dppz](2+) to d(GTCGAC)(2) induced significant broadening of the Me(2)phen and dppz resonances and large up field shifts of the dppz resonances, consistent with the metal complex binding through intercalation of the dppz ligand. Also indicative of intercalation are the observed up field shifts of the T-2 and G(4) imino protons and the 17 degreesC increase in the melting temperature of the hexanucleotide upon addition of the metal complex. NOE cross-peaks from the Me(2)phen protons were only observed to hexanucleotide minor groove H1' and H4'/H5'/H5 protons in NOESY spectra of the hexanucleotide with added metal complex. In addition, NOEs were also observed between the H13/14 protons of the dppz ligand and the hexanucleotide major groove T(2)methyl and sugar H2'/H2 protons. From the combined NMR data it is concluded that the dppz-based ruthenium(II) complex Delta-[Ru(Me(2)phen)(2)dppz](2+) intercalates from the minor groove of the hexanucleotide mini-duplex d(GTCGAC)(2).