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 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 (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.

Recent developments in anion induced capsular self-assemblies

“…Tren based L-alanine amino acid backboned electronwithdrawing group attached hexa-amide receptors 43-47 (Chart 12) are explored by our group towards anion binding. 91 Appreciable binding between receptors and Cl À , AcO À , BzO À , and HSO evidence of a Cl À complex of the pentafluorophenyl attached receptor 43 shows the formation of Cl À encapsulated unimolecular capsule (Fig. 20).…”

A Couple of Tripodal and Dipodal Fluorescent Sensors for Sequential “On‐Off‐On” Response to Cu2+ and ATP/ADP Recognition in Aqueous Solution

“…Besides that, tris (2‐amino‐ethyl) amine (tren) is another most used scaffold for the design of three‐dimensional receptors. By attachment of functional groups to the tren unit to modify the binding sites and even the receptors’ conformation, those acyclic tripodal receptors have been reported to exhibit specific binding ability towards different types of guests, such as tetrahedral oxoanions (NO 3 − , PO 4 3− and SO 4 2− ), halide ions (F − and Cl − ), divalent oxalate (C 2 O 4 2− ), and metal ions (Cu 2+ and Hg 2+ ) . Until now, the exploration of tripodal ligands for nucleoside polyphosphates recognition is still rare.…”

Chloride Encapsulation by a Tripodal Tris(4-pyridylurea) Ligand and Effects of Countercations on the Secondary Coordination Sphere

“…This tripodal structure has proven to be a promising scaffold for anion binding due to its favorable conformation for multiple hydrogen bonds, and many tren-based receptors with a variety of anion-binding sites such as amine, amide, urea, and thiourea groups, etc. have been synthesized. − Such receptors not only can complementarily encapsulate oxoanions (sulfate, carbonate, and phosphate) but also display excellent binding abilities to the spherical halide ions. For instance, Beer et al reported that a tripodal tris(amido-benzo-15-crown-5) ligand can cooperatively bind chloride, iodide, or perrhenate anions, while Fabbrizzi et al studied the incipient and definitive proton transfer of urea-fluoride interaction with tripodal ligands.…”