Stereoisomeric separation and chiral recognition mechanism study of star cyclodextrin polymer as the chiral stationary phase

Abstract

Background

As the derivatives of cyclodextrin (CD), cyclodextrin polymers (CDPs) effectively increase the concentration of CD units and construct supramolecular structures with unique stereoselectivity by the structure design. CDPs have shown significant potential in chiral separation, however, the process of stereoselective interactions on chiral stationary phases (CSPs) and the specific contribution of intermolecular forces are still a challenge issue. A comprehensive understanding of the chiral recognition mechanism of CDPs will help to optimize chiral separation conditions and design new CSPs.

Results

The star CDP with a supermolecular structure was synthesized by grafting β-CD onto the external 6-position hydroxyl groups using β-CD as the parent nucleus. The enhanced host-guest recognition ability of CD supramolecular polymer structure provided better inclusion interaction and increased chiral recognition of the isomers. The Star-CD CSP with star CDP as a chiral ligand performed satisfactory stereoisomer separation ability with the separation factor (α) up to 2.0 for various quinoline alkaloid isomers and 1.89 for catechins. To elucidate its chiral separation mechanism, molecular docking was used to construct the three-dimensional visual models of the binding sites and the contribution of non-covalent interactions between Star-CD CSP and quinoline alkaloid isomers. In addition, the formation sites of non-covalent interactions on the CD monomers of the polymer side chains were confirmed from the actual geometric structure by analyzing the NMR chemical shift changes before and after the formation of complexes between Star-CD polymers and isomers. Combined with the mutual evidence of molecular simulation and chiral NMR, the specific recognition mechanism of selector-selectand complexes was comprehensively expounded.

Significance

The multi-mode CSP based on cyclodextrin supramolecular structure provides new ideas for the stereoisomeric separation of complex chiral components with multiple chiral centers in natural products. Not limited to the macroscopic performance of the chromatographic separation, molecular docking explored the theoretical model of chiral recognition from the molecular level. The chiral NMR analysis confirmed the credibility of the model from the geometry structure, and then the recognition mechanism of multi-mode CSP was fully elaborated combining the above three aspects.