Novel Y-shaped nanomicelles based on γ-cyclodextrin as chiral selector and pseudostationary phase for enantioseparation in capillary electrophoresis

In this work, we synthesized a novel type of Y-shaped nanomicelles via an esterification reaction, with γ-cyclodextrin (γ-CD) as the hydrophilic group and branched long chain carboxylic acids as the hydrophobic groups. These ester compounds can self-assemble into nanomicelles in aqueous solution, simultaneously serving as a chiral selector and pseudostationary phase in capillary electrophoresis (CE) for enantioseparation. The Y-shaped nanomicelles were systematically characterized using fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR), particle size analysis, scanning electron microscope (SEM), transmission electron microscope (TEM), foaming effect and Tyndall effect. Due to the presence of branched chains, the hydrophobic chains of the Y-shaped nanomicelles exhibited increased hydrophobicity, and the hydrophobic interaction between the long chains in the cores was also enhanced. As a result, the stability of the Y-shaped nanomicelles was higher, reducing their tendency to dissociate. They also demonstrated a superior drug loading capability, thereby more effectively serving as a pseudostationary phase. Compared to the single γ-CD system and conventional nanomicelles system, the separation of nine model drugs in the Y-shaped nanomicelles system was significantly improved. We used racemic promethazine as a model drug and studied the drug loading of native γ-CD, conventional nanomicelles, and Y-shaped nanomicelles through high performance liquid chromatography. Additionally, the encapsulation effect was investigated using several methods such as particle size analysis, TEM, NMR, elemental analysis and thermogravimetric analysis. These results confirmed a higher distribution of enantiomers in the Y-shaped nanomicelles. This study demonstrates the superiority of Y-shaped nanomicelles in CE for enantioseparation and represents an important step toward the development of novel chiral recognition materials.