Meso Stereoisomer as a Probe of Enantioselective Threading Intercalation of Semirigid Ruthenium Complex [μ-(11,11‘-bidppz)(phen)4Ru2]4+

Abstract

Upon interaction with calf thymus DNA the Lambda,Lambda-enantiomer of the semirigid binuclear ruthenium complex [mu-(11, 11'-bidppz)(phen)(4)Ru-2](4+) has previously been shown to reorganize from an initial groove bound geometry into an intercalative binding mode, threading one of its bulky Ru(phen)(2) moieties through the core of the DNA. We have now found that all three stereoisomers, Delta,Delta; Lambda,Lambda; and Delta,Lambda (meso), are intercalated in their final modes of binding to calf thymus DNA, poly(dA-dT)(2), poly(dG-dC)(2), as well as poly(dI-dC)(2) indicated by linear dichroism, circular dichroism, and luminescence. For all three stereoisomers, studied in detail with poly(dA-dT)(2), the bridging bidppz ligand is intercalated in anti conformation, leaving one Ru(phen)(2) Moiety in each groove. This final binding geometry is characterized by a distinct clockwise roll of the Ru(phen)(2) moiety in the minor groove, similar to the roll earlier observed for the dppz ligand in [Ru(phen)(2)dppz](2+). Using the meso stereoisomer as an enantioselective probe, it is shown that the Lambda moiety prefers to insert itself deeply into the minor groove while the Delta moiety, in the major groove, is somewhat displaced from the center of the DNA helix. The preceding, metastable bound geometries are concluded to be in the major groove for calf thymus DNA, poly(dG-dC)(2), and poly(dI-dC)(2), with the Delta,Delta form displaying an angle of the bidppz bridge relative the DNA helix axis of about 50degrees, whereas the corresponding angles for the meso- and Lambda,Lambda-forms in calf thymus DNA are around 65degrees, suggesting an orientation in the groove more parallel to the bases. By contrast, in poly(dA-dT)(2) none of the stereoisomers exhibits any distinguishable initial groove binding mode, but all seem to bind by threading intercalation directly.