Conformational changes in a Pseudo[1]catenane induced by ethyl acetate and temperature: A combined HPLC and electronic circular dichroism study

Stereochemistry plays a pivotal role in the recognition properties of macrocyclic systems bearing multiple stereogenic elements. This study investigates a chiral pseudo[1]catenane based on a pillar[5]arene core covalently fused to a second macrocycle containing two carboxylic acid groups. The molecule contains three stereogenic elements: the planar stereogenicity of the pillararene macrocycle, a helical (P/M) stereogenicity induced by macrocycle closure, and central stereogenicity arising from the two stereocenters introduced by the side chain. Its synthesis yields two pairs of enantiomers, the main product being the racemic mixture of the enantiomers with identical configurations at both stereocenters of the side chain. The presence of COOH groups facilitates the selective binding of linear diamino guests, highlighting the potential of chiral pseudo[1]catenanes in molecular recognition. Understanding the conformational behavior of this system is crucial for its application in molecular recognition and sensing. Results: A multidisciplinary approach combining HPLC on an immobilized polysaccharide-based stationary phase (Chiralpak IA) and electronic circular dichroism was used to characterize the dynamic stereochemistry of the molecule. Two dominant conformers, designated in and out, defined by the location of the alkyl chain inside or outside the macrocyclic cavity, exhibited stability at room temperature. Their relative abundance shifted with varying ethyl acetate content in hexane. Lowering the HPLC column temperature from sub-ambient to cryogenic conditions resulted in each conformer splitting into two distinct peaks, revealing additional stereoisomeric species. Dynamic chromatographic profiles observed between − 7 ◦C and − 22 ◦C showed interconversion plateaus indicative of on-column isomerization. Computational simulation of these profiles enabled the estimation of the thermodynamic activation data associated with the conformational transitions. Significance: This study thoroughly examines the stereodynamic behavior of a multifunctional chiral pillar[5] arene derivative, demonstrating how solvent composition and temperature influence its conformational equilibrium. By integrating chromatographic and chiroptical techniques, we present a model for studying stereoisomeric interconversion in dynamic systems. These findings are valuable for designing chiral molecular hosts and devices that respond to external guests, with potential applications in enantioselective recognition and sensing.