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

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 peptidecoupling reaction between tripodal triscarboxylic acids and a calix[6]trisamine subunit. Several C-3- or C-3 nu-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.