Acid–Base Controllable Recognition Properties of a Highly Versatile Calix[6]crypturea

Versatile concave receptors with binding properties that can be controlled by external stimuli are rare. Herein, we report on a calix6]crypturea ( 1 ) that features two different binding sites in close proximity, that is, a tris(2‐aminoethyl)amine (tren)‐based tris‐ureido cap that provides convergent hydrogen‐bond‐donor sites and a hydrophobic cavity suitable for the inclusion of organic guests. The binding properties of this heteroditopic receptor have been evaluated by NMR spectroscopic studies. Compound 1 behaves as a remarkably versatile host that strongly binds neutral molecules, anions, or contact ion pairs. Within each family of guests, compound 1 is able to discriminate between different guests with a high degree of selectivity. Indeed, neutral molecules that possess hydrogen‐bond donor and acceptor groups, chloride anions, and linear ammonium ions associated to F^? or Cl^? are particularly well recognized. In comparison with all the related receptors, compound 1 displays several unique features: 1) charged or neutral species are also recognized in polar or protic solvents, 2) thanks to the flexibility of the calixarene structure, induced‐fit processes allow the binding of large, biologically relevant ammonium salts such as neurotransmitters, and 3) the protonation of the basic cap leads to a positively charged receptor, 1? H⁺, which is reluctant to host anions and in which host properties are now governed by strong charge–dipole interactions with the guests. In other words, compound 1 presents an acid–base controllable tris‐ureido recognition site protected by a hydrophobic corridor that can select guests through induced‐fit processes. Thus, its versatile host properties can be allosterically controlled by protonation and selective guest‐switching processes are possible. To illustrate all these remarkable features, a sophisticated three‐pole supramolecular switch, based on the interconversion of host–guest systems displaying either charged or neutral guests, is described.