A Study on the Chiral Recognition Mechanism of Enantioseparation of Adrenaline and Its Analogues Using Capillary Electrophoresis

Abstract

Since the first report 1) in 1985, capillary electrophoresis (CE) enantioseparation has become a very important area during the last two decades. In CE enantioseparation, the chiral selector can be directly added to the running buffer to provide chiral environment. Thus the two enantiomers can be separated owing to the difference in the interactions between chiral selectors and enantiomers. The most widely used chiral selectors are cyclodextrins (CDs) and various derivatives.2-7) Many papers on CE enantiomeric separation focused on optimization of experimental methods, for example, the type and concentration of CDs, buffer pH, ionic strength, etc. [8][9][10][11][12][13][14] Vescina et al. reported the CE enantiomeric separation of 35 basic pharmaceutical compounds using a total of 26 different CD derivatives with different functional groups and degrees of substitution.15) The experimental conditions were chosen based on literature reports and their own experience and more than 1000 CE experiments were involved. Ren and Liu investigated the effects of pH, b-CD concentration, electrolyte concentration, and methanol concentration on the chiral separation of dioxypromethazine enantiomers using capillary electrophoresis.16) Wioleta reported the application of carboxymethyl-b-CD as a chiral selector in capillary electrophoresis for enantiomer separation of selected neurotransmitters.17) The experimental factors have been optimized, such as the type and concentration of chiral selector, concentration of borate buffer, content of methanol, pH of electrolyte, and method of sample introduction into the capillary.17) However, the literature studies on enantiomeric separation of pharmaceutical compounds were limited by the explanation of how the enantiomeric separation occurred. The current study used a molecular docking technique to gain insight into the selector-enantiomer interaction energy and provided useful supporting information for enantiomeric separations.In this report, b-CDs were used as the chiral selectors and adrenaline and its analogues as the objects. The course of host-guest inclusion was determined by means of a molecular docking technique and thus the interaction energy was calculated by molecular mechanics calculations. Based on the results, the mechanism of chiral recognition is discussed. ExperimentalChemicals Adrenaline, noradrenaline and isopropyladrenaline were purchased from Shanghai Hefeng Pharmaceuticals Co., Ltd. Terbutaline was obtained from Shanghai Institute for Drug Control. Tris reagent was obtained from Shanghai Shisheng Cell Biotechnique Co., Ltd. b-CD was purchased from Suzhou Flavorings Factory; 2,3,6-trimethyl-b-CD was synthesized in our laboratory based on references 18,19) and the product was identified based on IR, NMR, and MS, which provided the physiochemical data such as the melting point of 156 to 157°C and IR (cm Ϫ1) of 2985, 2930, 2830, 1466, 1365, 1320, 1160, 1140, 1110, 1070. The uncoated fused-silica capillary was purchased from Hebei Yongnian Optical Fiber Factory.Apparat...

Cyclodextrins in capillary electrophoresis enantioseparations – Recent developments and applications

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Enantioseparation of new triadimenol antifungal active compounds by electrokinetic chromatography and molecular modeling study of chiral recognition mechanisms

“…Several reviews discussed the contribution of chiral CE in combination with molecular modeling to a better understanding of the chiral recognition mechanisms with CDs as chiral selectors. Our research group previously reported the study on the chiral recognition mechanism of enantioseparation of four adrenaline analogs , five β‐adrenergic antagonists , and a new antifungal drug iodiconazole using the molecular docking technique. A new mathematical model has been established on the basis of molecular mechanics calculations, and proved to possess good ability to predict the experimental resolution of enantioseparation .…”

Pairwise interaction enthalpies of enantiomers of β‐amino alcohols in DMSO + H2O mixtures at 298.15 K

“…Chiral recognition is a fundamental phenomenon in life sciences on the basis of the enantioselective complexation of a chiral molecule with a chiral selector . It can be studied by various techniques, such as UV–vis, fluorescence anisotropy (FA), gas liquid chromatography (GLC), high performance liquid chromatography (HPLC), circular dichroism (CD), nuclear magnetic resonance (NMR), mass spectroscopy (MS), capillary electrophoresis (CE), capillary zone electrophoresis (CZE), calorimetry, and so on. In these years, microcalorimetric techniques, in particular isothermal titration calorimetry (ITC), become available, which open the way for measurements of processes associated with small heat changes from microcalories to millicalories per mole .…”