Synthesis of a Preorganized Hybrid Macrobicycle with Distinct Amide and Amine Clefts: Tetrahedral versus Spherical Anions Binding Studies

A new C3v 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–, SO42–) 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.