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 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 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 (complex 1) and encapsulation of Br(-) in the ammonium cleft of H3L (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.