Nyssen Nicolas, Ajami Daniela, Ardelean Adrien, Desroches Florent, Li Jing, Luhmer Michel, Reinaud Olivia, Jabin Ivan
Laboratoire de Chimie Organique, Université libre de Bruxelles (ULB), Avenue F.D. Roosevelt 50, CP160/06, B-1050 Brussels, Belgium.
Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Université de Paris, 45 rue des Saints Pères, 75006 Paris, France.
J Org Chem. 2021 Sep 3;86(17):12075-12083. doi: 10.1021/acs.joc.1c01418. Epub 2021 Aug 19.
A molecular capsule based on a calix[6]arene core closed at the small rim by a three-point coordinated metal ion and at the large rim by a three-point covalent capping is described. It is derived from a trisimidazole funnel complex capped by a trenamide unit that prevents in/out exchange of guest molecules through the large rim. A detailed comparative study with three different calixarenes provides a unique opportunity for (i) comparing the binding ability of two different coordination sites in well three-dimensional (3D)-structured macrocyclic receptors and (ii) evaluating the impact of a covalent closing of one rim of a funnel receptor while the other rim is closed by weaker coordination bonds. Indeed, this study allowed for highlighting various interesting new features. It is first shown that the trenamide site can bind a metal ion such as Zn by itself. This involves a 1:1 coordination of the metal ion to the three carbonyl groups of the amide functions, which undergo trans-to-cis isomerization and are partially embedded in the calix core. When the trisimidazole core is present, the Zn ion preferentially binds at the small rim, thus closing the cavity. Guest ligand exchange must then occur through a decoordination/recoordination process of the metal ion. The modification and rigidification of the calixarene conformation induced by the large rim capping strengthen the metal ion coordination at the small rim. This also leads to a selective metallo-receptor that readily binds EtNH under conditions where PrNH is not recognized at all. The increased rigidity of the receptor, however, weakens the host-guest interactions, precluding important induced-fit behaviors that are at work in the parent, large rim opened, funnel complex.
描述了一种基于杯[6]芳烃核心的分子胶囊，其小端通过三点配位金属离子封闭，大端通过三点共价封端封闭。它源自由三乙撑四胺酰胺单元封端的三咪唑漏斗配合物，该单元可防止客体分子通过大端进行进出交换。与三种不同杯芳烃的详细比较研究提供了一个独特的机会，用于（i）比较在三维（3D）结构良好的大环受体中两个不同配位位点的结合能力，以及（ii）评估漏斗受体一个边缘共价封闭而另一个边缘通过较弱配位键封闭的影响。实际上，这项研究突出了各种有趣的新特征。首先表明，三乙撑四胺酰胺位点本身可以结合金属离子，如锌。这涉及金属离子与酰胺官能团的三个羰基的1:1配位，酰胺官能团发生反式到顺式异构化并部分嵌入杯芳烃核心。当存在三咪唑核心时，锌离子优先结合在小端，从而封闭空腔。然后客体配体交换必须通过金属离子的去配位/再配位过程发生。大端封端引起的杯芳烃构象的修饰和刚性增强了金属离子在小端的配位。这也导致了一种选择性金属受体，在完全不识别丙胺的条件下能容易地结合乙胺。然而，受体刚性的增加削弱了主客体相互作用，排除了在母体大端开放的漏斗配合物中起作用的重要诱导契合行为。
