Development And Application Of “Click” Derived ?-cyclodextrin Chiral Stationary Phases And Simulation Study Of Its Chiral Separation Mechanism

In this study,“thiol-ene” green click reaction has been applied to the preparation of a serious of new ?-cyclodextrin chiral stationary phases(?-CD-CSPs),including natural cationic ?-CD-CSP1 and phenyl isocyanate functional groups derived ?-CD-CSP2 and ?-CD-CSP3.The preparation process has been proved to be succinct and mild,and the prepared CSPs are structurally stable and efficient.CSP1 is applicable to RP and HILIC separation mode,meanwhile CSP2 and CSP3 can both be used in RP,NP,PO and HILIC mode.The prepared CSPs have been applied to high performance liquid chromatography(HPLC)and made enantioseparation of multiple types of enantiomers,including neutral analytes such as isoxazolines and flavonids,acidic enantiomers such as dansyl amino acids,as well as basic ones such as ?-blockers,add up to 71 pairs.Due to the cation group on the link of CSP1,it displayed big retention factors and good resolutions for acid enantiomers,especially with smaller p H than 6.50 and lower proportion of organic phase.For isoxazolines enantiomers,this is the first report of its enantioseparation on CD-CSPs,and even more amazing,Ar-OPr(a category of isoxazolines)obtained very high selectivity(?(28)18.6)and great resolution(38.7sR(28))on CSP2 and CSP3.In order to make clear the mechanism of enantioseparation of ?-CD,from the perspective of molecular modeling,molecular dynamic simulation(MD)combined with the free energy calculation method adaptive biasing force(ABF)has been used to explore enantioseparation behavior of ?-CD in Me OH/H2 O mixed solvent.The molecular dynamics software NAMD and molecular field CHARMM have been used.Two possible host-gest interact orientation have been considered,the MD gived potential of mean force(PMF)curves of the complexation of ?-CD and guest flavanones.From the PMF we got the association constants and association free energys of flavanones with ?-CD.According to the calculated results,R-flavanone got smaller association free energy,which exactly corresponds to the HPLC results that R-flavanone has shorter elution time.This discovery indicates that the method used in current research can be employed to predict the elution order of enatiomers in the course of chiral chromatography,which would have good value of actual application.In addition,the hydrogen bonds that formed between flavanones and ?-CD has been further observed.