A research team of Professor Chen Lei from the School of Pharmaceutical Science and Technology (SPST) designed a multi-mode CSP based on the supramolecular structure of star cyclodextrin polymer (Sil-Star-CD CSP), which provides a new idea for the stereoisomeric separation of complex chiral components with multiple chiral centers in natural products.
The active ingredients of natural medicines have complex chemical structures, and the presence of multiple chiral centers leads to various stereoisomeric components, which poses significant challenges to their chiral quality control. Cyclodextrin polymers (CDPs), as an essential type of cyclodextrin (CD) derivative, increase the concentration of CD units while retaining the cavity structure of CDs, making it easy to form inclusion complexes with guest molecules. Meanwhile, the supramolecular structure further improves the stereoselectivity of CD-based chiral stationary phases (CSPs), which is conducive to the chiral separation of complex stereoisomeric components in natural products. A comprehensive understanding of the intrinsic chiral recognition mechanism will facilitate the design of highly stereoselective CSPs and promote the development of chiral quality control of natural products. However, dissecting the stereoselective interaction processes of CSPs at the molecular level and elucidating the contribution of intermolecular interactions is a challenging issue.
Professor Chen’s team designed a multi-mode CSP based on the supramolecular structure of star cyclodextrin polymer (Sil-Star-CD CSP). The Sil-Star-CD CSP performed satisfactory stereoisomeric selectivity with the separation factor (α) up to 2.0 for various quinoline alkaloid isomers and 1.89 for catechins. Not limited to the macroscopic performance of the chromatographic separation, molecular docking was utilized to explore the theoretical models of chiral recognition at the molecular level and reveal the intermolecular interaction types and their specific contributions. The chiral NMR technique was applied to analyze the actual geometrical structure changes of the “chiral stationary phase-enantiomer” complexes. It verified the credibility of the theoretical model given by the molecular docking. The above three aspects fully elaborate the chiral recognition mechanism of the multi-mode Sil-Star-CD CSP, and provide a new solution for the design of supramolecular chiral ligands and the intermolecular recognition mechanism study.
Fig 1.Schematic diagram of stereoisomeric separation and chiral recognition mechanism of quinine and
quinidine on the star cyclodextrin polymer chiral stationary phase.
This work has been published in the journal ofAnalytica Chimica Actatitled “Stereoisomeric separation and chiral recognition mechanism study of star cyclodextrin polymer as the chiral stationary phase.”The School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University is the first communication unit. PhD student Hui Bai is the first author and associate professor Lei Chen is the corresponding author of the paper.
DOI：10.1016/j.aca.2024.343249
By School of Pharmaceutical Science and Technology
Editor: Sun Xiaofang
