Evidence for chiral discrimination of ruthenium(ii) polypyridyl complexes by DNA

Abstract

Here we report on the synthesis and enantiomeric resolution of metal complexes of the type [Ru(bpyMe₂)₂L]²⁺ (where bpyMe₂ = 4,4′-dimethyl-2,2′-bipyridine and L = 1,10-phenanthroline (phen), dipyrido[3,2-a:2′3′-c]quinoxaline (dpq), dipyrido[3,2-a:2′3′-c](6,7,8,9-tetrahydro)phenazine (dpqc) or dipyrido[3,2-a:2′3′-c]phenazine (dppz)). DNA-paper chromatography, absorption spectroscopy, gel electrophoresis and viscometry of linear DNA were used to assess the association and affinity for DNA of the aforementioned complexes. Optical resolution of the complexes was achieved by solvent recycled chromatography using Sephadex cation exchange resin and disodium (−)-O,O′-dibenzoyl-L-tartrate. Paper chromatography successfully elucidated the relative binding affinities of the metal complexes investigated in the following order phen (0.68) < dpq (0.36) < dpqc (0.14) < dppz (0.09). Absorption spectroscopy experiments indicated that each of the complexes were in close association with the DNA. Electrophoresis of the plasmid DNA incubated with the Δ complexes of dppz or dpqc show unwinding. The Λ-isomer of dppz resulted in smearing due to less effective binding whereas the Λ-isomer of dpqc showed no unwinding at all. Unexpectedly, rac-[Ru(bpyMe₂)₂(dpq)]²⁺ showed greater unwinding than either isomer. DNA-viscosity experiments provided evidence that both the Δ and Λ-isomers of dppz and dpqc bind by intercalation. However, Δ and Λ-[Ru(bpyMe₂)₂(dpq)]²⁺ bind through different modes, the Δ isomer by intercalation and the Λ isomer by partial intercalation. The conclusions that can be drawn from this is that the extended methyl groups in the 4- and 4′-positions on the bpyMe₂ ligand are critical in eliciting different enantiomeric interactions with the walls of the DNA grooves.