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

Article abstract of DOI:10.1021/jo401504f

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 A 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 [H ₂L]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.