Dendritic Pillar[6]Arenes with Fixed Planar Chirality for Stereoselective Inclusions in Water: A Case of Facile Differentiation of Cocaine Adulterants, Levamisole and Dexamisole

Abstract

AbstractWe describe the preparation, conformational dynamics, and stereoselective recognition characteristics of water‐soluble pillar[6]arenes pS–212− and pR–212−. These two novel and diastereomeric cavitands comprise a 2,5‐bis(ethoxy)pillar[6]arene core with one of six phenylene ring conjugated to two hexaanionic dendrons. Each dendron includes an (S)−glutamic acid amidated with two tris‐carboxylic Behera's amines. Cavitands pS–212− and pR–212− were obtained in six synthetic steps and resolved by column chromatography. The results of 1H NMR and circular dichroism spectroscopic measurements are in line with pS/pR–212− having unidirectional orientation of alkoxy substituents (i.e., planar chirality) and no observable interconversion for, at least, 2 weeks. Computational studies supported with 1H DOSY NMR measurements revealed that sufficiently bulky dendrons require high activation energy to pass through the pillararene's cylindrical cavity therefore inhibiting rotation of the phenylene holding them. With the unique and chiral binding pocket, pS–212− (pR–212−) formed inclusion complexes with cocaine adulterants levamisole and dexamisole (Kd > mM), with their racemic mixture showing separate 1H NMR spectroscopic resonances. In this way, dendritic pillar[6]arenes can be used as chiral shift reagents for determining enantiopurity of pharmaceuticals but also for examining a variety of chiral recognition processes, sensing of chiral molecules, and stereoselective sequestrations in aqueous media.