Application And Mechanism Of Chiral Separation For Triadimenol Compounds By Capillary Electrophoresis

Nowadays the production and usage of optically pure drugs is the trend of new drugs research.Because the bioactivity of chiral drugs is closely related to the stereo structures,the study on chiral drugs has become one of new directions of new drugs research internationally.Chiral separation of chiral drugs with increasing importance in pharmaceutical research,is now a hot topic in international analysis science.Capillary electrophoresis(CE) is a fast separation technique with high efficiercy and sensitivity which developed rapidly in last two decades.CE is one of the best chiral separation analysis technique in application prospect,and displayed great potency.In CE enantioseparation,the chiral selector is dissolved in the running buffer to provide chiral environment.So the two enantiomers can be separated owing to the difference of the interactions between chiral selectors and enantiomers and thus the difference of electrophoretic mobillities.Cyclodextrins(CDs) are the most widely used chiral selectors.Presently CE enantioseparation is focused on experimental research between different kinds of cyclodextrins and enantiomers,while lacking of mechanism research systematically.In this study,application research on chiral separation by CE was carried out with a series of triazole compounds.(1)Capillary electrophoresis for chiral separation of 22 triazole compounds with fluorine substituents in side chain using three neutral CDs and three charged CDs,the main factors in fluencing the CE enantioseparation were investigated,such as pH,concentration of CDs and ionic strength et al and established a powerful CE chiral separation method for triazole compounds.(2)Using the optimal CE conditions to separate the 13 triazole compounds which have no fluorine substituents in side chain and 12 triazole compounds which have fluorine substituents in side chain.Comparing the differences of the triazoles,we try to explore the CE enantioseparation regularity,and presume the possible combination point between CDs and enantiomers.The course of host-guest inclusion was determined by means of molecular docking and thus association energy was calculated by molecular mechanics.With the computer-assisted molecular modeling technique,the inclusion mechanism between CDs and enantiomers was microscopically investigated,the theory about chiral recognition was discussed.Weight the steric energy and electros energy of the 25 pairs of enantiomers and according this we built up a mathematic model which could analyze the relationship between resolution and steric energy and electros energy.So we can predict the possibility of chiral separation,comparing with the results of CE enantioseparation,we can demonstrate the mathematic model have high capability to predict the chiral separation. The results were as follows:firstly,"three-point interaction" was well developed,secondly, it was demonstrated that there existed a certain correlation between the difference of steric energy and chiral separation of CM-β-CD to the serial of triadimenol compounds.