Allosterically Controlled Capture of Mutually Repulsive Guests With Positive Cooperativity and Ultrahigh Affinity

ABSTRACT A hexacationic cage incorporating three urea units can encapsulate two mutually repulsive anions in close proximity through a combination of hydrogen bonding and electrostatic interactions. This leads to exceptionally high binding affinities, with a K 1 × K 2 value of approximately 10 20 M ‒2 in MeCN‐ d 3 , for pairs of Cl ‒ or F ‒ anions. In its unbound state, the cage adopts a collapsed conformation stabilized by intramolecular interactions. These interactions are disrupted upon binding of the first anion guest, inducing an unfolded conformation that facilitates the binding of the second guest. Consequently, despite repulsion, the second Cl ‒ anion binds more strongly than the first by three orders of magnitude. This work presents a straightforward strategy for mimicking biological allosteric regulation and offers insights into the underlying physicochemical principles. The strong halide binding enables several applications. The cage can extract F ‒ from CaF 2 , suggesting a route to utilize fluorine from fluorspar for fluorochemical synthesis that bypasses the generation of hazardous HF. Furthermore, the cage can extract Cl ‒ or Br ‒ anions from organic halides, thereby stabilizing the corresponding carbocations and accelerating reactions involving these intermediates. In addition, the high affinity of the cage for halide anions released from fire suppressants provides for corrosion resistance.