Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
J Am Chem Soc. 2012 Jul 18;134(28):11430-43. doi: 10.1021/ja302347q. Epub 2012 Jul 2.
Using dynamic combinatorial chemistry, mixtures of dipeptide monomers were combined to probe how the structural elements of a family of self-assembled [2]-catenanes affect their equilibrium stability versus competing non-catenated structures. Of particular interest were experiments to target the effects of CH-π interactions, inter-ring hydrogen bonds, and β-turn types on [2]-catenane energetics. The non-variant core of the [2]-catenane was shown only to adopt type II' and type VIII turns at the β-2 and β-4 positions, respectively. Monomers were designed to delineate how these factors contribute to [2]-catenane equilibrium speciation/stability. Dipeptide turn adaptation studies, including three-component dynamic self-assembly experiments, suggested that stability losses are localized to the mutated sites, and that the turn types for the core β-2 and β-4 positions, type II' and type VIII, respectively, cannot be modified. Mutagenesis studies on the core Aib residue involved in a seemingly key CH-π-CH sandwich reported on how CH-π interactions and inter-ring hydrogen bonds affect stability. The interacting methyl group of Aib could be replaced with a range of alkyl and aryl substituents with monotonic affects on stability, though polar heteroatoms were disproportionately destabilizing. The importance of a key cross-ring H-bond was also probed by examining an Aib for l-Pro variant. Inductive affects and the effect of CH donor multiplicity on the core proline-π interaction also demonstrated that electronegative substituents and the number of CH donors can enhance the effectiveness of a CH-π interaction. These data were interpreted using a cooperative binding model wherein multiple non-covalent interactions create a web of interdependent interactions. In some cases, changes to a component of the web lead to compensating effects in the linked interactions, while in others, the perturbations create a cascade of destabilizing interactions that lead to disproportionate losses in stability.
使用动态组合化学，将二肽单体混合物组合在一起，以探究一系列自组装[2] - 套索的结构元素如何影响其平衡稳定性与竞争的非套索结构。特别感兴趣的实验是针对 CH-π 相互作用、环间氢键和β-转角类型对[2] - 套索能量学的影响。[2] - 套索的非变体核心仅显示在β-2 和β-4 位置分别采用 II'型和 VIII 型转角。设计单体以描绘这些因素如何有助于[2] - 套索平衡种/稳定性。二肽转角适应研究，包括三组分动态自组装实验，表明稳定性损失局限于突变位点，并且核心β-2 和β-4 位置的转角类型，分别为 II'型和 VIII 型，不能被修饰。涉及似乎关键的 CH-π-CH 三明治的核心 Aib 残基的诱变研究报告了 CH-π 相互作用和环间氢键如何影响稳定性。Aib 中涉及的相互作用甲基可以用一系列烷基和芳基取代基替代，对稳定性具有单调影响，尽管极性杂原子不成比例地降低稳定性。还通过检查 Aib 对 l-Pro 变体来研究关键交叉环 H-键的重要性。诱导效应和 CH 供体多样性对核心脯氨酸-π 相互作用的影响也表明，电负性取代基和 CH 供体的数量可以增强 CH-π 相互作用的有效性。这些数据使用协同结合模型进行解释，其中多个非共价相互作用创建了一个相互依存的相互作用网络。在某些情况下，网络中某个组件的变化会导致链接相互作用中的补偿效应，而在其他情况下，这些扰动会产生一系列不稳定的相互作用，导致稳定性不成比例地损失。
