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[3,2-a,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 structures of Λ/Δ-1, indicating that [Ru(bpy)₂(7-CH₃-dppz)]²⁺ is a non-specific intercalator for poly(U-A ∗ U) investigated in this work.

中文翻译：

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Ru（II）复合物[Ru（bpy）2（7-CH 3 -dppz）] 2+的两个对映异构体与RNA poly（UA⁎U）三元体相互作用的生物物理见解

摘要

为了确定通过手性的Ru（II）多吡啶配合物，一个新的一对对映异构体的影响RNA的三链结构的稳定的因素，Δ-的[Ru（联吡啶）₂（7-CH ₃ -dppz）] ²⁺（Δ - 1 ; bpy = 2,2'-联吡啶，7-CH ₃ -dppz = 7-甲基-联吡啶[3,2- a，2'，3'- c ]吩嗪）和Λ-[Ru（bpy）₂（ 7-CH ₃ -dppz）] ²⁺（Λ -1），已在这项工作中进行了合成和表征。已经通过光谱学和流体动力学方法研究了两种对映异构体与RNA poly（UA⁎U）三链体的结合特性（其中“-”表示沃森-克里克碱基配对，“⁎”表示Hoogsteen碱基配对）。在此研究中使用的条件下，尽管∆ -1的结合亲和力高于Λ -1的结合亲和力，但两种对映体的吸收光谱变化在与三链体结合时并没有很大的不同。荧光滴定和粘度实验提供了令人信服的证据，证明对映体与三链体之间确实存在插入结合。然而，熔融实验表明两种对映异构体选择性地稳定了三链体。对映体∆ -1稳定模板双链体和三链体的第三链，同时对于稳定模板双链体更有效。与∆ -1形成鲜明对比的是，Λ -1使三链体稳定，而对第三链的稳定没有任何影响，这表明该人非常喜欢稳定模板的双链体而不是第三链。此外，与Λ -1相比，∆ -1的三重态稳定效应更为明显。获得的结果表明Ru（II）聚吡啶基配合物的取代基效应和手性在三链体稳定中起重要作用。

图形摘要

配合物Λ/Δ-[Ru（bpy）₂（7-CH ₃ -dppz）] ²⁺（Λ/ Δ - 1 ; bpy = 2,2'-联吡啶，7-CH ₃ -dppz = 7-甲基-联吡啶制备了[3,2- a，2'，3'- c ]吩嗪）作为聚（UA ∗ U）三重态的稳定剂。结果表明，三链体稳定性取决于Λ/Δ- 1的手性结构，表明[Ru（bpy）₂（7-CH ₃ -dppz）] ²⁺是一种非特异性嵌入剂，用于研究聚（UA ∗ U）。这项工作。