Allosteric and Electrostatic Cooperativity in a Heteroditopic Halogen Bonding Receptor System

A halogen bonding (XB) heteroditopic receptor, consisting of a 1,3‐bis‐iodo‐triazole benzene XB anion binding site covalently appended via a flexible methylene group with two benzo‐15‐crown‐5 (B15C5) cation binding moieties, and its hydrogen bonding receptor analogue, are used to delineate the mechanisms of cooperativity for alkali metal halide ion‐pair recognition. Extensive cation, anion and ion‐pair (1)H NMR titration investigations demonstrate the combination of allosteric pre‐organisation, via 1 : 1 stoichiometric intramolecular potassium and rubidium metal cation bis‐B15C5 sandwich complexation, in concert with favourable electrostatics and XB potency, results in a remarkable enhancement of halide anion binding affinity by a factor of at least 700. By contrast, a notably diminished halide anion affinity enhancement factor of just 15 is observed with the corresponding 1 : 1 stoichiometric sodium cation complexed receptor system, where the smaller sized cation singly occupies one B15C5 unit and only an electrostatic contribution to cooperativity is possible. These observations serve to illustrate that allosteric pre‐organisation capability, electrostatic attraction and XB mediated anion recognition are important strategic design features to incorporate in future high‐fidelity heteroditopic ion‐pair receptor development.