Synthesis of a preorganized hybrid macrobicycle with distinct amide and amine clefts: tetrahedral versus spherical anions binding studies

Abstract

A new C_3v symmetric amido-amine hybrid macrobicycle, L is synthesized toward anion recognition in its protonated states. L contains tri-amide and tetra-amine clefts separated by p-phenylene spacers. The solid-state structure of methanol-encapsulated L exhibits an overall cavity length of ∼12.0 Å where the amide and amine -NH protons are converged toward the center of the respective cavities. Conformational analysis of L in solution is established by NOESY NMR. Anion binding of [H₃L]³⁺ with spherical (Cl^–, Br^–, I^–) and tetrahedral (ClO₄^–, SO₄^2–) anions are carried out by isothermal titration calorimeter in dimethylsulfoxide. The association of halides with [H₃L]³⁺ is endothermic and entropy driven. However, association of tetrahedral anions is exothermic in nature and both entropy- and enthalpy-driven. The overall association constants show the following order: HSO₄^– > Br^–> Cl^– ≈ ClO₄^–. Single crystal X-ray structures of ClO₄^– and Br^– complexes of protonated L show encapsulation of ClO₄^– in the amide cleft of [H₂L]²⁺ (complex 1) and encapsulation of Br^– in the ammonium cleft of [H₃L]³⁺ (complex 2). Further, preorganization of L toward encapsulation of spherical and tetrahedral anions is established by comparing its amide, amine, and overall cavity dimensions with 1 and 2.