A series of amino acid functionalized tripodal hexaamide anion receptors: ion-pair-assisted capped-cleft formation by a pentafluorophenyl-functionalized amide

Abstract

A new series of tris(2-aminoethyl)amine (tren)-based L-alanine amino acid backboned tripodal hexaamide receptors (L1–L5) with various attached moieties based on electron-withdrawing fluoro groups and lipophilicity have been synthesized and characterized. Detailed binding studies of L1–L5 with different anions, such as halides (F⁻, Cl⁻, Br⁻, and I⁻) and oxyanions (AcO⁻, BzO⁻ (Bz=benzoyl), NO₃⁻, H₂PO₄⁻, and HSO₄⁻), have been carried out by isothermal titration calorimetric (ITC) experiments in acetonitrile/dimethylsulfoxide (99.5:0.5 v/v) at 298 K. ITC titration experiments have clearly shown that receptors L1–L4 invariably form 1:1 complexes with Cl⁻, AcO⁻, BzO⁻, and HSO₄⁻, whereas L5 forms a 1:1 complex only with AcO⁻. In the case of Br⁻, I⁻, and NO⁻, no appreciable heat change is observed owing to weak interactions between these anions and receptors; this is further confirmed by ¹H NMR spectroscopy. The ITC binding studies of F⁻ and H₂PO₄⁻ do not fit well for a 1:1 binding model. Furthermore, ITC binding studies also revealed slightly higher selectivity of this series of receptors towards AcO⁻ over Cl⁻, BzO⁻, and HSO₄⁻. Solid-state structural evidence for the recognition of Cl⁻ by this new category of receptor was confirmed by single-crystal X-ray structural analysis of the complex of tetrabutylammonium chloride (TBACl) and L1. Single-crystal X-ray diffraction clearly showed that the pentafluorophenyl-functionalized amide receptor (L1) encapsulated Cl⁻ in its cavity by hydrogen bonds from amides, and the cavity of L1 was capped with a TBA cation through hydrogen bonding and ion-pair interactions to form a capped-cleft orientation. To understand the role of the cationic counterpart in solution-state Cl⁻ binding processes with this series of receptors (L1–L4), a detailed Cl⁻ binding study was carried out with three different tetraalkylammonium (Me₄N⁺, Et₄N⁺, and Bu₄N⁺) salts of Cl⁻. The binding affinities of these receptors with different tetralkylammonium salts of Cl⁻ gave binding constants with the TBA cation in the following order: butyl>ethyl>methyl. This study further supports the role of the TBA countercation in ion-pair recognition by this series of receptors.