Biophysical insights into the interaction of two enantiomers of Ru(II) complex [Ru(bpy) 2 (7-CH 3 -dppz)] 2+ with the RN

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Biophysical insights into the interaction of two enantiomers of Ru(II) complex [Ru(bpy)2(7‑CH3‑dppz)]2+ with the RNA poly(U‑A⁎U) triplex Zhan Dong1 · Xiaohua Liu2 · Lifeng Tan3,4  Received: 22 August 2020 / Accepted: 28 September 2020 © Society for Biological Inorganic Chemistry (SBIC) 2020

Abstract  To determine the factors affecting the stabilization of RNA triple-stranded structure by chiral Ru(II) polypyridyl complexes, a new pair of enantiomers, ∆-[Ru(bpy)2(7-CH3-dppz)]2+ (∆-1; bpy = 2,2′-bipyridine, 7-CH3-dppz = 7-methyl-dipyrido[3,2a,2′,3′-c]phenazine) and Λ-[Ru(bpy)2(7-CH3-dppz)]2+ (Λ-1), have been synthesized and characterized in this work. Binding properties of the two enantiomers with the RNA poly(U-A⁎U) triplex (where “-“ denotes the Watson − Crick base pairing and “⁎” denotes the Hoogsteen base pairing) have been studied by spectroscopy and hydrodynamics methods. Under the conditions used in this study, changes in absorption spectra of the two enantiomers are not very different from each other when bound to the triplex, although the binding affinity of ∆-1 is higher than that of Λ-1. Fluorescence titrations and viscosity experiments give convincing evidence for a true intercalative binding of enantiomers with the triplex. However, melting experiments indicated that the two enantiomers selectively stabilized the triplex. The enantiomer ∆-1 stabilize the template duplex and third-strand of the triplex, while it’s more effective for stabilization of the template duplex. In stark contrast to ∆-1, Λ-1 stabilizes the triplex without any effect on the third-strand stabilization, suggesting this one extremely prefers to stabilize the template duplex rather than third-strand. Besides, the triplex stabilization effect of ∆-1 is more marked in comparison with that of Λ-1. The obtained results suggest that substituent effects and chiralities of Ru(II) polypyridyl complexes play important roles in the triplex stabilization. Graphic abstract Complexes Λ/Δ-[Ru(bpy)2(7-CH3-dppz)]2+ (Λ/Δ-1; bpy = 2,2′-bipyridine, 7-CH3-dppz = 7-methyl-dipyrido[3,2-a,2′,3′-c] phenazine) were prepared as stabilizers for poly(U-A * U) triplex. Results suggest the triplex stabilization depends the chiral

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0077​5-020-01825​-9) contains supplementary material, which is available to authorized users. * Lifeng Tan [email protected] 1



College of Chemistry, Xiangtan University, Xiangtan 411105, People’s Republic of China

2



Academic Affairs Office, Xiangtan University, Xiangtan 411105, People’s Republic of China

3

Key Lab of Environment‑Friendly Chemistry and Application in Ministry of Education, Xiangtan University, Xiangtan 411105, People’s Republic of China

4

Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Xiangtan University, Xiangtan 411105, People’s Republic of China





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JBIC Journal of Biological Inorganic Chemistry

structures of Λ/Δ-1, indicating that [Ru(b