Enantiomers of Ruthenium(II) Complex [Ru(bpy) ₂ (qip)] ²⁺ Exhibit Highly Chiral‐Selective Effects on the Stabilization of Third Strand of Triplex RNA Poly(U‐A*U)

Two chiral Ru(II) complexes bearing a quinoline ring, Λ‐[Ru(bpy) 2 (qip)] 2+ (Λ‐ 1 ) and Δ‐[Ru(bpy) 2 (qip)] 2+ (Δ‐ 1 , where bpy = 2,2′‐bipyridine and qip = 2‐(quinolin‐3‐yl)‐1H‐imidazo[4,5‐f][1,10]phenanthroline), were prepared. Their interactions with triplex RNA were systematically investigated using ultraviolet–visible (UV–Vis) spectroscopy, luminescence spectroscopy, nucleic acid thermal denaturation experiments, and circular dichroism (CD) spectroscopy. The data from UV–Vis titrations support intercalation as the binding mode for both enantiomers with triplex RNA. Further quantitative analysis revealed that the complexes exhibited significant chiral selectivity, with Δ‐ 1 demonstrating a stronger binding affinity for triplex RNA than Λ‐ 1 . Luminescence titration experiments further supported the binding of the complexes via intercalation. CD analysis demonstrated that both Λ‐ 1 and Δ‐ 1 could significantly induce conformational changes in the triplex RNA, and strong intermolecular interactions between the complexes and triplex RNA were observed, further suggesting a potential intercalative binding mode. The thermal denaturation results revealed that the third strand was selectively and markedly stabilized. The stabilization of the third strand in the triplex RNA was significantly enhanced by both enantiomers, while exerting negligible effects on the template duplex. The chiral ruthenium(II) complex developed in this study exhibits specific stabilization of triplex RNA, providing an effective strategy for stabilizing triplex RNA structures.