Capillary Chiral Separation of Agrochemicals: Complementary Insights From Molecular Modeling and NMR

ABSTRACT The study investigates the capillary electrophoretic enantioseparation of agrochemicals (dichloroprop and mecoprop) using modified cyclodextrins 2‐hydroxypropyl‐β‐cyclodextrin (CD‐1), heptakis (2,3‐di‐O‐methyl)‐β‐cyclodextrin (CD‐2), heptakis (2,3‐di‐O‐methyl‐6‐sulfo)‐β‐cyclodextrin (CD‐3), and heptakis (2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (CD‐4) in 2‐(N‐morpholino)ethanesulfonic acid (MES) buffer. Migration times varied depending on the selector type and inclusion complex type and stability, reflecting differences in enantiomer–selector interaction strengths. The reversal of enantiomer migration order observed among the cyclodextrins suggested that even small structural differences in the chiral selectors influenced changes in intermolecular interactions and complex stability. This reversal order is useful for understanding the mechanisms. The separations were due to inclusion complexes with neutral cyclodextrins, while electrostatic interactions were responsible for negatively charged cyclodextrins. Docking and ROESY‐NMR studies were used to provide supportive structural insight into the nature of chiral recognition mechanisms. The docking provided general structural information about the potential binding modes of these systems. However, native β‐cyclodextrin was used for the ROESY‐NMR studies because it produced very clear spectra, allowing the comparison of the basic interaction patterns among the various β‐cyclodextrin derivatives. Overall, the results demonstrated that capillary electrophoresis (CE) is a sensitive technique for investigating intermolecular interactions and gaining insight into enantioselective processes.