Exploiting the Dimerization Characteristic of H₂PO₄^– to Promote Its Selective Recognition by a Tetra-Amido Macrocycle

Creating a confined cavity that matches the size and binding site of the substrate is a prevalent strategy to achieve selective recognition of specific anions. However, this not only requires sophisticated receptor design but also leads to challenging receptor synthesis. In this contribution, by utilizing the dimerization characteristic of H₂PO₄^–, we demonstrate that selective recognition of H₂PO₄^– can also be achieved in DMSO by a synthetically simple tetra-amido macrocycle (<b>1</b>). By reaction condition optimization, the yield of the final cyclization reaction was improved. Through ¹H NMR titration studies, we exhibit a sharp contrast in the binding affinity between H₂PO₄^– and other anions, as well as the exclusive recognition of H₂PO₄^– from competitive environments containing various anions. Through Job’s plot, nonlinear fitting, single-crystal X-ray diffraction, computational study, variable temperature NMR, and DOSY NMR, the binding mechanism of <b>1</b>+H₂PO₄^– was extensively studied, including binding stoichiometry (1:2 host–guest), stability constant (β₂ = 1.4 × 10⁵ M^–2), recognition sites, possible binding structure, and the corresponding hydrodynamic radius (<i>r</i>_H). Binding studies in DCM and 50% methanol/chloroform further support the proposed binding mechanism. This study therefore explores a new approach to achieve selective recognition by taking advantage of the self-assembly characteristics of substrates.