Development of ruthenium probes designed to bind enantio- and stereospecifically to DNA

In the past decade, substitutionally-inert chiral ruthenium complexes have found valuable use as metalloprobes for the determination of causal factors governing smallmolecule recognition by DNA. Considerable work has derived from the initial reports of enantioselectivity observed between the Δ- and Λ-[Ru(phen)3]2+ ions and DNA [1–3], where it was concluded that the ght-handed (Δ) propeller form binds preferentially. The binding mode originally was depicted by one of the phen ligands stacking, or intercalating into DNA, with the remaining two making van der Waals contacts with the surface of the helical groove [2]. It was proposed that this enantiopreference arises from steric clashes that exist between the two external phen blades of the Λ-isomer and the ribo-phosphate backbone of the duplex. However, the structural basis for these effects remained uncertain and in order to investigate this, subsequent studies have led to the use of analogues of general form [Ru(L)2(L’)]2+, where L is 1,10-phenanthroline (phen) or 2,2’-bipyridine (bipy) and L’ is a planar bidentate with an enhanced aromatic surface area. The latter component serves as the intercalating chromophore and hence determines overall molecular binding affinity.