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), NO(3)(-), H(2)PO(4)(-), and HSO(4)(-)), 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 HSO(4)(-), whereas L5 forms a 1:1 complex only with AcO(-). In the case of Br(-), I(-), and NO(3)(-), no appreciable heat change is observed owing to weak interactions between these anions and receptors; this is further confirmed by (1)H NMR spectroscopy. The ITC binding studies of F(-) and H(2) PO(4)(-) 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 HSO(4)(-). 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 (Me(4) N(+), Et(4) N(+), and Bu(4) N(+)) 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.