Chiral ruthenium(II) complexes as stabilizers for an RNA triplex: In contrast to Λ-enantiomer, Δ-enantiomer stabilizes the Watson-Crick duplex and the Hoogsteen strand without significant preference

Abstract

To further determine the factors governing the triplex stabilization by chiral ruthium(II) polypyridyl complexes, two new dppz-beased binding reagents, Δ-[Ru(bpy)2(6-NO2-dppz)]2+ (Δ-1; bpy = 2,2′-bipyridine; 6-NO2-dppz = 6-nitro-dipyrido-3,2-a,2′,3′-c]phenazine) and Λ-[Ru(bpy)2(6-NO2-dppz)]2+ (Λ-1), have been synthesized and characterized in this work. Binding properties of the two enantiomers Δ-1 and Λ-1 with the RNA poly(U)•poly(A)*poly(U) triplex have been studied by spectroscopic technologies and viscosity measurements as well as melting measurements. Spectral titrations and viscosity experiments as well as light-scattering experiments show that although the two enantiomers bind to the triplex through an intercalative mode, the binding affinity of Δ-1 toward the triplex is slightly higer than that of Λ-1. Moreover, melting measurements show that the two enantiomers exhibit different stabilization effects on the triplex under the same conditions. The enantiomer Δ-1 stabilizes the triplex without significant preference, thereby almost equally stabilizing the Watson-Crick base-paired duplex (the template duplex) and the Hoogsteen base-paired strand (third-strand) of the triplex. In contrast to Δ-1, Λ-1 shows preference for stabilizing the template duplex rather than third-strand to a large extent. This suggests that the racemic complex [Ru(bpy)2(6-NO2-dppz)]2+ is similar as a non-specific metallointercalator for the triplex investigated in this study. The results obtained in this work show that in addition to chiralities of Ru(II) polypyridyl complexes, substituent effects of the main ligands also play important roles in altering the ability and selectivity of the metal complex enantiomers to stabilize the triplex.