Binding Mode of [Ruthenium(II) (1,10-Phenanthroline)2L]2+ with Poly(dT*dA-dT) Triplex. Ligand Size Effect on Third-Strand Stabilization

The binding of homochiral [Ru(II)(1,10-phenanthroline)(2)L](2+) complexes {where L = 1,10-phenanthroline (phen), dipyrido[3,2-a:2',3'-c]phenazine (DPPZ) or benzodipyrido[3,2-a:2',3'-c]phenazine (BDPPZ)} to poly(dT*dA-dT) triplex has been investigated by linear and circular dichroism and thermal denaturation. Analysis of the linear dichroism spectra indicates that the extended DPPZ and BDPPZ ligands lie approximately parallel to the base-pair and base-tripler planes consistent with intercalation which is also supported by strong hypochromism in the interligand absorption bands with either duplex or tripler. The spectral properties of any of the metal complex enantiomers were similar for binding to either duplex or tripler DNA, indicating that the third strand, which occupies the major groove of the template duplex, has little effect on the binding geometries and hence supports the hypothesis that the metal complexes all bind from the minor groove with the DPPZ and BDPPZ ligands intercalated but without intercalation in the case of [Ru(phen)(3)](2+). Third-strand stabilization depended on the nature of the third substituted phenanthroline chelate ligand but was not directly related to its size, with stabilizing power increasing in the order phen < BDPPZ < DPPZ. This observation further supports intercalation of the extended ligands from the minor groove of the tripler since the extended BDPPZ ligand that would protrude into the major groove of the template would have greater steric interference than DPPZ with the third DNA strand.