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

Abstract

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(-), 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.