Department of Chemistry , University of Copenhagen , Universitetsparken 5 , DK-2100 Copenhagen Ø , Denmark.
J Org Chem. 2019 Mar 1;84(5):2577-2584. doi: 10.1021/acs.joc.8b02797. Epub 2019 Feb 19.
Binding of anions using macrocyclic structures with a nonpolar interior using the CH···anion interaction as the recognition motif has gained popularity in the past few years, and such receptors often rely on a subtle interplay between enthalpic and entropic factors. For these types of receptors solvation of both the anion and the binding pocket of the macrocyclic host play important roles in the overall energetic picture of the binding event. Systematic chemical modifications of synthetic receptors that are able to bind anions in a variety of solvents is an important tool to gain understanding of the factors that determine the supramolecular chemistry of anions. Here we present the chiral macrocyclic structure biotin-l-sulfoxide[6]uril as a host molecule that binds anions in both water and in organic solvents. Biotin-l-sulfoxide[6]uril is prepared in a highly diastereoselective one-pot synthesis from the macrocycle biotin[6]uril. We compare the binding properties with that of biotin[6]uril, also studied in acetonitrile and in aqueous buffer at neutral pH. The biotin-l-sulfoxide[6]uril generally exhibits stronger recognition of anions in acetonitrile, but weaker binding in water as compared to the biotin[6]uril macrocycle. We have studied the binding events using a combination of NMR spectroscopy, isothermal titration calorimetry (ITC), and computational methods.
近年来，利用具有非极性内部的大环结构通过 CH···阴离子相互作用作为识别基序来结合阴离子的方法已经流行起来，并且此类受体通常依赖于焓和熵因素之间的微妙相互作用。对于这些类型的受体，阴离子和大环主体的结合口袋的溶剂化在结合事件的整体能量图中起着重要作用。对能够在各种溶剂中结合阴离子的合成受体进行系统的化学修饰是了解决定阴离子超分子化学的因素的重要工具。在这里，我们提出手性大环结构生物素-l-亚砜[6]脲作为一种主体分子，它可以在水和有机溶剂中结合阴离子。生物素-l-亚砜[6]脲是通过大环生物素[6]脲的高非对映选择性一锅合成制备的。我们将其与生物素[6]脲的结合性质进行了比较，生物素[6]脲也在乙腈中和中性 pH 的水性缓冲液中进行了研究。与生物素[6]脲大环相比，生物素-l-亚砜[6]脲通常在乙腈中对阴离子表现出更强的识别能力，但在水中的结合能力较弱。我们使用 NMR 光谱、等温滴定量热法 (ITC) 和计算方法相结合来研究结合事件。
