A novel supramolecular system that acts as a biomimetic receptor for neutral guests is presented. The functionalization of t-butyl-calix[6]arene (X6H6) at the lower rim in alternate position by methyl (Me) and 2-methylene-1-methyl-1H-imidazole (Imme) yielded the new ligand X(6)Me(3)Imme(3). It provided a neutral tris(imidazole) coordination site associated with a conic cavity, thereby mimicking the active center of zinc proteins. Upon reaction with Zn(ClO4)(2)(H2O)(6), an air-stable dicationic zinc-aqua complex [Zn(X(6)Me(3)Imme(3))(H2O)](ClO4)(2) was obtained. The highly acidic Zn2+ center was constrained in a tetrahedral environment with a labile site oriented toward the inside of the calix[6]arene structure. The hydrophobic pocket acted as a selective molecular funnel for neutral molecules. H-1 NMR spectroscopy studies showed the easy exchange of the aqua ligand for amines, alcohols, amides, or nitriles. The selectivity of the exchange process is based on both the guest's binding ability to the metal center and its shape and size. Two of these ternary complexes were characterized by X-ray diffraction analysis: [Zn(X(6)Me(3)Imme(3)) (NCC2H5)](ClO4)(2) and [Zn(X(6)Me(3)Imme(3))(NH2C7H15)](ClO4)(2). Hydrogen bonds between the acidic protons of the coordinated guest and the calixarene phenoxyl group suggest an important role in the stabilization of these dicationic complexes that do not undergo deprotonation.