A Series of Amino Acid Functionalized Tripodal Hexaamide Anion Receptors: Ion-Pair-Assisted Capped-Cleft Formation by a Pentafluorophenyl-Functionalized Amide

A new series of tris(2-aminoethyl)amine (tren)-based L-alanine amino acid backboned tripodal hexaamide receptors (L1L5) with various attached moieties based on electron-withdrawing fluoro groups and lipophilicity have been synthesized and characterized. Detailed binding studies of L1L5 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 L1L4 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 NO3-, 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 (L1L4), 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.