Allosteric tuning of the intra-cavity binding properties of a calix[6]arene through external binding to a ZnII center coordinated to amino side chains

Molecular recognition by calix[6]arene-based receptors bearing three primary alkylamino side chain arms (1) is described. Complexation of Zn(II) ion provides the dinuclear mu-hydroxo complex 2G(OH), XRD characterization of which, together with solution studies, provided evidence of its hosting of neutral polar organic guests G. Treatment of this complex with a carboxylic acid or a sulfonamide (XH) results in the formation of mononuclear species 3G(X), one of which (X = Cl) has been characterized by XRD. A dicationic complex 3G(RNH2) is obtained upon treatment of 2G(OH) with a mixture of an alkylamine and a strong acid. Each of these Zn(II) complexes features a tetrahedral metal ion bound to the three amino arms of ligand 1 and to an exogenous ligand (either HO-, X-, or RNH2) sitting outside of the cavity. As a result, the metal ion structures the calixarene core, constraining it in a cone conformation suitable for guest hosting. The receptor properties of these compounds have been explored in detail and are compared with those of the trisammonium receptor 1G(3H+), based on the same calixarene core, as well as those of the trisimidazole-based dicationic Zn funnel complexes. This study reveals very different host properties, in spite of the common hydrophobic, pi-basic, and hydrogen-bonding acceptor properties of the calixarene cores. A harder external ligand produces a less polarized receptor that is consequently particularly sensitive to the hydrogen-bonding ability of its guest. The less electron-rich the apical ligand, and a fortiori the trisammonium host, the more sensitive the receptor to the dipole moment of the guest. All this stands in contrast with the funnel Zn complexes, in which the coordination link plays a dominant role. It is also shown that the asymmetry of an exo-coordinated enantiopure amino ligand is sensed by the guest. This supramolecular system nicely illustrates how the receptor properties of a hydrophobic cavity can be allosterically tuned by the environment.