Selective Hetero-Trisfunctionalization of the Large Rim of a Biomimetic Calix[6]arene Using Host−Guest Chemistry as a Synthetic Tool

Selective Hetero-Trisfunctionalization of the Large Rim of a Biomimetic Calix[6]arene Using Host−Guest Chemistry as a Synthetic Too

Synthesis of <i>C</i>_3<i>v</i>-Symmetrical 1,3,5-Tris-Protected Calix[6]arene-Based Molecular Platforms

Few synthetic methodologies that yield tris-functionalized C3v-symmetrical calix[6]­arenes have been reported. In this work, three allyl protecting groups are selectively placed in 1,3,5 alternate positions of three pristine calix[6]­arenes, each differing by their substituent on the large rim, resulting in three new C3v-symmetrical molecular platforms. Removal of the protecting allylic groups gives access to sophisticated calix[6]­arenes that can be further modified. The potential of these new C3v-symmetrical molecular platforms is notably exemplified through the development of a new family of calix[6]­arene-based N ligands

Tris(triazolyl) Calix[6]arene-Based Zinc and Copper <i>Funnel</i> Complexes: Imidazole-like or Pyridine-like? A Comparative Study

Huisgen dipolar cycloaddition leads straightforwardly to new funnel complexes based on the calix[6]arene macrocycle bearing three functionalized triazoles as coordinating units at the small rim. Coordination to Zn(II) and Cu(I) cations was studied using 1H NMR and IR spectroscopies and cyclic voltammetry. The nature of the substituents on the triazole ring affects the behavior of the ligands and their coordinating ability and controls the host–guest properties of the metal receptors for exogenous substrates. Depending on their substitution pattern but also on the metal ion and the guest ligand, the triazole-based systems behave either imidazole-like or pyridine-like. The ease of preparation and the versatility of 1,4-disubstituted-1,2,3-triazoles with tunable steric and electronic properties make them promising candidates for further applications from biology to materials

A Water-Soluble Calix[4]arene-Based Ligand for the Selective Linear Coordination and Stabilization of Copper(I) Ion in Aerobic Conditions

A number of serious diseases are linked to copper homeostasis dysfunction. The design of copper­(I)-selective chelators is of particular interest not only for the creation of therapeutic objects but also as useful tools to gain insights into the coordination of copper­(I) in a biological medium. A water-soluble Cu^I-selective ligand that associates strong Cu^I binding at pH = 7.4 (10¹⁴ M^–1), insensitivity to air, and selectivity toward Cu^II and other biologically relevant cations is described

Supramolecular Control of Hetero-multinuclear Polytopic Binding of Metal Ions (Zn^II, Cu^I) at a Single Calix[6]arene-Based Scaffold

A Calix[6]­arene scaffold was functionalized to provide a tridentate binding site at the small rim and three bidentate chelate sites at the large rim of the cone to generate a heteropolytopic ligand. Its complexation to one equivalent of Zn^II at the small rim yields a <i>funnel</i> complex displaying both host–guest properties and preorganization of the three chelate groups at the large rim. These two aspects allowed the full control of the binding events to regioselectively form dinuclear Zn^II and heteropolynuclear Zn^II/Cu^I complexes. The heteropolynuclear systems all rely on the host–guest relationship thanks to the induced-fit behavior of the calix cavity. With the short guest MeCN, the large rim is preorganized into a trigonal tris-triazole core and accommodates a single Cu^I ion. A long guest breaks this spatial arrangement, and three Cu^I ions can then be bound at the tris-bidentate triazole-dimethylamine site at the large rim. In a noncoordinating solvent however, the tetranuclear complex is submitted to scrambling and the addition of exogenous π-acceptor ligands is required to control the binding of Cu^I in a well-defined environment. Hindrance selectivity was then induced by the accessibility at the small rim site. Indeed, while CO can stabilize Cu^I at both coordination sites, PPh₃ cannot fit into the cavity and forces Cu^I to relocate at the large rim. The resulting well-defined symmetrical tetranuclear complex thus arises from the quite remarkable selective supramolecular assembly of nine partners (1 Zn^II, 3 Cu^I, 1 calixarene, 1 guest alkylamine, 3 PPh₃)

Electrochemically Triggered Double Translocation of Two Different Metal Ions with a Ditopic Calix[6]arene Ligand

A ditopic ligand based on a calix[6]arene with three imidazoles (Im) appended at the small rim and three triazoles (Tria) at the large one is able to form selectively two stable heterodinuclear complexes with ZnIIIm/CuITria and CuIIIm/ZnIITria. In the CuI case, the zinc cation is preferentially coordinated at the Im site while the copper is bound at the Tria site. The situation is the opposite when CuII is used. The position of the two cations within the complex can be electrochemically switched via the oxidation−reduction of the copper cation between oxidation states +I and +II. The presence of the zinc cation is crucial (i) to control the bistability of the system by an allosteric structuring role and (ii) to promote the metal switch since the monocopper complex exhibits reversible behavior with Cu located at the imidazole site in both oxidation states. This represents the first example of a double translocation of two different metal cations

Guest-Triggered Zn^II Translocation and Supramolecular Nuclearity Control in Calix[6]arene-Based Complexes

Two new polytopic ligands based on a calix[6]­arene scaffold were synthesized. The truncated cone-shaped calixarene was functionalized at its small rim by a tris-imidazole site, aimed at generating a tetrahedral Zn^II complex, where a fourth labile site inside the cavity is accessible through the funnel provided by its large rim. Tridentate aza ligands (either two or three) were then grafted at this large rim (the entrance of the cavity). Zn^II coordination studies, monitored by ¹H NMR spectroscopy, showed unprecedented behavior in this family of heteropolytopic ligands. Indeed, it gives access to complexes of various nuclearities in acetonitrile, where zinc binding is under the supramolecular control of the guest. It is first shown that, in the absence of a good guest donor (a primary amine), Zn^II binding is favored at the large rim where two tridentate nitrogenous groups can form an octahedral complex. The addition of a long guest such as heptylamine induces the quantitative translocation of the Zn^II ion from the large rim octahedral (<i>O</i>_h) site to the small rim tetrahedral (<i>T</i>_d) site provided by the trisimidazole core and the guest ligand. With 2 equiv of Zn^II, well-defined dinuclear complexes were obtained and isolated, with one Zn^II ion bound at each rim. Interestingly, it is shown that the binding mode at the large rim is under the supramolecular control of the guest bound at the small rim (with short guests, the <i>O</i>_h environment is obtained at the large rim, whereas long guests disrupt this core through an induced-fit process); the partially included and dangling alkyl chain opens the large rim (entrance of the cavity) and pushes apart the tridentate moieties. As a result, a guest-induced switch of Zn^II binding mode occurs and frees one of the tridentate groups from coordination, allowing further extension of the complex nuclearity

A Ditopic Calix[6]arene Ligand with <i>N</i>-Methylimidazole and 1,2,3-Triazole Substituents: Synthesis and Coordination with Zn(II) Cations

The first member of a new class of ditopic calix[6]arene has been synthesized, which is decorated with three N-methylimidazoles at the small rim and three 1,4-disubstituted-1,2,3-triazoles at the large rim. The coordination of a first Zn(II) cation selectively takes place at the small rim. Addition of a second equivalent results in the complexation of the three triazoles, providing a rare example of 1,2,3-triazole ligands embedded within a supramolecular system

Calorimetric Study on Coordination of Tridentate Imidazolyl Calix[6]arene Ligands to Zinc Ion in Organic Solvents

Complexation of three kinds of tris(imidazolyl)calix[6]arenes containing alternate p-substituents (Calix-tBu, R1 = R2 = tert-butyl; Calix-NH2, R1 = tert-butyl, R2 = NH2; Calix-NO2, R1 = tert-butyl, R2 = NO2) with Zn(ClO4)2(H2O)6 in acetonitrile, methanol, and THF was investigated via isothermal titration calorimetry (ITC). For the coordination of these calixarene ligands to Zn(II) in acetonitrile, typical one-phase exothermic titration curves were obtained, indicating the formation of 1:1 ligand–Zn(II) complexes accompanied by large conformational changes of the ligands. In contrast, the complexation in methanol was endothermic and dominated by favorable entropy changes. The entropy gains were achieved by extensive desolvation from both Zn(II) and the ligands. ITC measurements suggest a 2:1 ligand–Zn(II) complex formation in THF in the presence of excess ligands (Calix-NH2 and Calix-NO2). The 2:1 complexes were converted to 1:1 complexes upon further addition of Zn(ClO4)2(H2O)6. The results indicate the important role of a coordinating solvent (acetonitrile) for direct formation of the 1:1 complexes under the conditions of excess ligand. Complexation of a ditopic ligand (Calix-Tri) with three triazole moieties on the wider rim was also studied via ITC. The first coordination of the imidazole moieties to Zn(II) was an exothermic process. This was followed by the entropically favorable coordination of the triazole moieties to the divalent cation. We have also investigated exchange of the fourth ligand (H2O) of the Zn(II) complex of Calix-NH2 with butylamine, heptylamine, acetonitrile, and acetamide in a noncompetitive solvent, THF. The ΔH0 tended to decrease upon increasing the electron-pair-donating ability of the guest ligand, whereas it was also affected by an entropic term due to restricted rotation of the guest ligand inside the calixarene cavity

Supramolecular Assistance for the Selective Monofunctionalization of a Calix[6]arene Tris-carboxylic Acid-Based Receptor

The selective functionalization of macrocyclic receptors remains extremely challenging because it generally requires the transformation of one and only one functional group among several identical groups. Recently, some of us described that the host–guest properties of a calix[6]­arene-based Zn complex could be exploited for its selective monofunctionalization. Herein, we report on the extension of this synthetic strategy to a calix[6]­arene-based receptor displaying a different recognition pattern with its guest. More precisely, a calix[6]­arene tris-carboxylic acid-based receptor bearing three azido groups at the large rim was selectively monofunctionalized through an intramolecular thermal Huisgen reaction with a hexynNH₃⁺ ion accommodated into the cavity. This work shows that the monofunctionalization methodology can also be performed efficiently with host–guest systems involving ionic/H-bonding interactions, and it is thus not limited only to the use of metal–ligand interactions. In other words, this supramolecular methodology can be used as a general tool for the selective functionalization of molecular receptors