Synthesis and characterization of chiral Ru(II) polypyridyl complexes and their binding and stabilizing effects toward triple-helical RNA.

Two novel chiral Ru(II) complexes, Λ- and Δ-[Ru(bpy)(7-CF-dppz)] (Λ-1 and Δ-1; bpy = 2,2'-bipyridine, 7-CF-dppz = 7-trifluoromethyl-dipyrido[3,2-a:2',3'-c]phenazine), were synthesized and characterized in this work. The binding and stabilizing effects of Λ-1 and Δ-1 toward the RNA poly(U)•poly(A)*poly(U) triplex were studied by various biophysical techniques. Absorption spectra and fluorescence quenching indicates that the binding affinity of Δ-1 is slightly higher than that Λ-1. Both enantiomers induce significant positive viscosity changes that are indicative of intercalative binding, whereas changes in the relative viscosities of the triplex are found to be more pronounced with Δ-1. Melting experiments indicate that the triplex stabilization effects of both enantiomers are significantly different from each other. With Λ-1, the stabilization of the Watson-Crick base-paired duplex (the template duplex) of the triplex shows a moderate increase, whereas the stabilization of the Hoogsteen base-paired strand (third-strand) exhibits slight decrease under the same conditions, suggesting Λ-1 prefers to stabilize the template duplex rather than third-strand. In stark contrast to Λ-1, Δ-1 can not only strongly stabilize the template duplex, but also moderately increase the third-strand stabilization, even so, which imply that Δ-1 also prefer to stabilize the template duplex instead of the third-strand. These suggest that the [Ru(bpy)(7-CF-dppz)] is similar as a non-specific metallointercalator the triplex studied in this work. Combined with our recent research, the obtained results further indicate that Δ- enantiomers rather than Λ-ones of Ru(II) polypyridyl complexes usually exhibit stronger binding and stabilizing effects toward the triplex.