Chiral separation of pharmaceuticals and agrochemicals using capillary electrophoresis: Migration order, modeling and...

Chiral separation of pharmaceuticals (acenocoumarin, coumatetralyl, and warfarin) and agrochemicals (mecoprop and dichloroprop) was achieved utilizing native cyclodextrins (α-, β-, and γ-CDs) as chiral selectors in capillary electrophoresis (CE); with a particular focus on enantiomer reversal order migration of mecoprop and dichloroprop. This is the first study to demonstrate the reversal migration order for these agrochemical compounds, which provides new insights into the chiral recognition mechanisms of native CDs. The best chiral separation was achieved on γ-CD with selectivity coefficient (α) ranging from 1.018 to 1.066, resolution factor from 1.40 to 2.06, and the number of theoretical plates from 10.597 to 95.890 (R-enantiomers) and 7.352 to 90.777 (S-enantiomers). The fused silica and polyvinyl alcohol-coated capillaries gave the best results with 200 mM MESS buffer [2-(N-morpholino)ethanesulfonic acid] buffer containing 0.1 % hydroxymethylcellulose (pH 3.0 and 4.5). The best resolution was of coumatetralyl, dichloroprop, and mecoprop with β-CD. Chiral recognition mechanisms were determined by modeling and NMR studies by considering acenocoumarin as an example. R-enantiomer of acenocoumarin migrated first with a -3.4 kcal/mol binding affinity and three hydrogen bonds with γ-CD, compared to the S-enantiomer, which exhibited a -3.6 kcal/mol binding affinity and four hydrogen bonds. This study provides valuable insights for the enantioselective analysis of the reported compounds and demonstrates the potential of CE for resolving unknown chiral samples. The reversal order of migration served as a key tool in determining the chiral separation mechanism.