Enantioseparation By Chromatography And Quantum Chemistry Applications In Chiral Recognition Mechanism

In this thesis,the deeper studies of recognition mechanism of chiral stationary phase were carried out by integrating chromatography and molecular modeling method,including the enthalpy-entropy compensation effects of statistic analysis,molecular simulation calculation and QSERRs methods.The nature of chiral recognition was stated from the molecular level in order to understand the positions and the forces of chiral recognition on the stationary phase.The separation of enantiomers of methyl mandelate,α-chloro-N-phenyl propanamide andα-chloropropionates on the Cyclodex B chiral column containing had been studied by gas chromatography.The effect ofα-chloropropionate structure and column temperature on the separation of enantiomers ofα-chloropropionates had been investigated.On the other hand,the thermodynamic parameters in the process of separation of enantiomers were determined in order to discuss driven power and chiral discrimination mechanism in the process of separation of enantiomers. The experimental results showed that the separation for enantiomers of methyl mandelate,α-chloro-N-phenyl propanamide and α-chloropropionate was enthalpy-driven process and there was enthalpy-entropy compensation.The host-guest complexation ofβ-cyclodextrin(β-CD) with enantiomers of ethylβ-chloropropionates((R/S)-ECPA) was successfully simulated by Quantum Mechanics PM3 method for the first time.Chiral recognization mechanism of(R/S)-ECPA enantiomers onβ-CD was investigated.The modeling results showed the stabilization complexation structures which formed with(R/S)-ECPA enantiomers andβ-CD were different.(R)-ECPA was located the cavity wide mouth end ofβ-CD to form associated molecule.(S)-ECPA was inserted inβ-CD cavity to form inclusion molecule.The stabilization energy of(S)-ECPA—β-CD complex was less than that of(R)-ECPA—β-CD.And,the chiral carbon in ECPA for(R/S)-ECPA—β-CD complexes was close to C(2) and C(3) in glucose unit.So,the chiral recognization mechanism was closely related to the chiral environment provided to C(2) and C(3) in the glucose unit and hydrogen bond forms of(R/S)-ECPA andβ-CD.Chiral recognization mechanism of Methylβ-cyclodextrin(PMBCD) with enantiomers of methylα-chloropropionates((R/S)-MCPA was simulated by Quantum Mechanics PM3 method for the first time.The modeling results showed the stabilization complexation structures which formed with(R/S)-MCPA enantiomers and PMBCD were different.The chiral carbon in MCPA for(R/S)-MCPA-β-CD complexes was close to C(2) and C(3) in glucose unit.So,the chiral recognization mechanism was closely related to the chiral environment provided to C(2) and C(3) in the glucose unit and inclusion degree to(R/S)-MCPA andβ-CD.In addition,and the interactive energy diference(ΔE) between two enantiomers was compared to predict the chromatographic elution-order. The results were in accordance with that of GC experiments.Theα-amino acids soluted-related structure descriptors parameters was computed by Hartree-Fock program(6-31G method) in Quantum chemistry,the QSERR modeling of chromatographic retention of the optical isomers ofα-amino acids on the crown chiral stationary phases and their molecular structure descriptors parameters were set with stepwise multiple linear regression method.The results showed there is better linear relationship between capacity factors of the optical isomers ofα-amino acids and their molecular structure descriptors parameters. The physical meaning of these molecular structure descriptors parameters in the QSERR modeling is definite.The QSERR modeling had better stability and predictability.The chromatographic retention and chiral discrimination mechanism in the separation process of the optical isomers ofα-amino acids on the crown stationary phases were investigated.