| Bioactivity of chiral drugs is closely related to the stereo structures. Nowadays the production and usage of optically pure drugs is the trend of new drugs research. The study on chiral drugs has become one of new directions of new drugs research internationally. Analysis of chiral drugs,with increasing importance in pharmaceutical research,is now a hot topic in international analysis science.At present analysis of chiral drugs is mainly achieved by two approaches:direct and indirect enantioseparation. Direct enantioseparation is simple,rapid,accurate and reliable. High performance liquid chromatography (HPLC) plays a leading role in direct enantioseparation,while the applications of capillary electrophoresis (CE) are increasing significantly. CE,developed rapidly hi last two decades,is a fast separation technique with high efficiency and sensitivity.In CE enantioseparation,the chiral selector (or additive) 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 mobilities. Cyclodextrins (CDs) are the most widely used chiral selectors. Presently CE enantioseparation is focused on experimental research between different lands of cyclodextrins and enantiomers,while lacking of mechanism research systematically.In this report,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 and the theory about chiral recognition was discussed. The results were as follows. Firstly,the mechanism of chiral recognition by CDs involved combination at multi-point and determination by one point. In chiral recognition by CDs,enantiomers and CDs formed reversible inclusion complexes with different structures and properties by inclusion within cavity and complexation outside of CDs. The inclusion can happen at multi-point,while the complexation at one point or multi-point. There must have difference of interaction at one complexation point outside to achieve chiral separation. This point can be the entire side chain or groups attached directly to chiral carbon. Secondly,compounds which can be chirally separated by CDs always have two major structural features:(l) hydrophobic skeleton such as benzene ring,can increase the association energy between molecules and CDs;(2)the large stereo groups connected with the asymmetric center provide certain van der Waals interactions;(3)auxiliary factors:the H-bond receptors on hydrophobic skeleton mayintroduce H-bond interactions with CDs so as to increase the association energy;(4) when the stereo group attached to the asymmetric center can't supply all energy for recognition,the group on the side chain which can form H-bond with CDs assisted the chiral recognition. The essence of chiral recognition and separation by CDs is owing to side chains,moreover hydrophobia skeleton can prolong the inclusion time and shorten the inclusion distance. Thirdly,it was demonstrated that there existed a certain correlation between the difference of association energy and chiral separation. Lastly,the main factors influencing the CE enantioseparation were investigated. The results showed the influence reduced according to the order:type of CDs,pH,concentration of CDs and ionic strength.Application research on analysis of isomer drugs by CE was carried out at the same time by the angles and demands of pharmaceutical analysis,such as determination of ephedrine and pseudoephedrine by mixed-substituents-p-CD CE,test of D-isomer impurity hi L-sulpiride,assay of oleanolic acid and malol hi fructus corni by CD-MEKC,determination of pseudoephedrine in BaiFuNing tablets,and separation of cis- and trans- TM. Enantiomer like ephedrine,pseudoephedrine and sulphide,isomer like ephedrine and pseudoephedrin...
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