Synthesis and Study of Calix[6]cryptamides: A New Class of Heteroditopic Receptors that Display Versatile Host–Guest Properties Toward Neutral Species and Organic Associated Ion‐Pair Salts

Abstract

The synthesis of a new family of molecular receptors, namely the calix[6]cryptamides, was achieved through an original [1+1] macrocyclization step that consists of a peptide-coupling reaction between tripodal triscarboxylic acids and a calix[6]trisamine subunit. Several C3- or C3v-symmetrical calix[6]arene-based compounds capped by a trisamido cryptand unit on the narrow rim have been obtained, with the more flexible partners leading to the best yields. These calix[6]cryptamides exhibit two favorably positioned binding sites for the complexation of organic-associated ion pairs in close proximity: a well-defined calix[6]arene cavity suitable for the inclusion of ammonium ions and a cryptamide unit for the coordination of anions. We demonstrate one example, chiral calix[6]cryptamide 12, that constitutes a heteroditopic receptor capable of cooperatively binding both a primary ammonium ion and its chloride counterion, thanks to a combination of polarization and induced-fit effects. In addition, the hydrophobic calixarene cavity of 12 can strongly bind neutral guests through hydrogen bonding and is capable of discriminating between different enantiomers. All these versatile host-guest properties differ greatly from those observed in the parent calix[6]azacryptands.

Emergence of Hemicryptophanes: From Synthesis to Applications for Recognition, Molecular Machines, and Supramolecular Catalysis

“…On the basis of the reaction between tris-acyl chloride and tris-amino compounds, Jabin and co-workers synthesized hemicryptophane 90 with a calix[6]­arene platform (Scheme ). The [1 + 1] macrocyclization reaction between calix[6]­arene 86 and CTV 87 was first performed under high dilution conditions, giving the hemicryptophane 90 in 15% yield after flash chromatography purification. With the aim of improving the yield, they also tested and optimized the reaction between calix[6]­trisamine 86 and CTV tris-acid 88 in the presence of peptide-coupling reagents such as PyBOP ((benzotriazol-1-yloxy)­tripyrrolidinophosphonium hexafluorophosphate) to produce 90 with a much better yield (46%).…”

“…The first complexation experiment was described in 1982 with hemicryptophane 1 , followed 26 years later by a second example reported by Le Gac and Jabin . Only recently, hemicryptophanes have been investigated as complexing agents for various chiral or achiral guests such as ammoniums, ,,, ion pairs, ,, zwitterions, ,,, carbohydrates, ,,, and C 60 or C 70 fullerenes .…”

“…The first complexation experiment was described in 1982 with hemicryptophane 1 , followed 26 years later by a second example reported by Le Gac and Jabin . Only recently, hemicryptophanes have been investigated as complexing agents for various chiral or achiral guests such as ammoniums, ,,, ion pairs, ,, zwitterions, ,,, carbohydrates, ,,, and C 60 or C 70 fullerenes . This section aims at reporting the complexation properties in the solid state and in a solution of hemicryptophane hosts, emphasizing the enantioselective recognition with enantiopure receptors.…”

Ion pair receptors

“…33), a receptor that was put forward as a host for neutral molecules and alkylammonium chloride ion pairs (alkyl = ethyl and propyl) 74. Receptor 62 contains a calix[6]arene subunit that is designed to act as a cation recognition site.…”

Molecular recognition of organic ammonium ions in solution using synthetic receptors

“…Even larger structures, based on this trimethoxy-calix[6]arene scaffold triple-bridged with a cyclotriveratrylen or connected to dimers via alkyl bridges, were applied for ammonium ion pair inclusion [ 348 ].…”