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

Abstract

A new <i>C</i>_3<i>v</i> symmetric amido-amine hybrid macrobicycle, <b>L</b> is synthesized toward anion recognition in its protonated states. <b>L</b> contains tri-amide and tetra-amine clefts separated by <i>p</i>-phenylene spacers. The solid-state structure of methanol-encapsulated <b>L</b> 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 <b>L</b> in solution is established by NOESY NMR. Anion binding of [H₃<b>L</b>]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 [H₃<b>L</b>]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 <b>L</b> show encapsulation of ClO₄^– in the amide cleft of [H₂<b>L</b>]²⁺ (complex <b>1</b>) and encapsulation of Br^– in the ammonium cleft of [H₃<b>L</b>]³⁺ (complex <b>2</b>). Further, preorganization of <b>L</b> toward encapsulation of spherical and tetrahedral anions is established by comparing its amide, amine, and overall cavity dimensions with <b>1</b> and <b>2</b>