Enantiomeric separation in high-performance liquid chromatography using novel β-cyclodextrin derivatives modified by R-configuration groups as chiral stationary phases

Two new chiral stationary phases (CSP) were successfully prepared through bonding β-cyclodextrin (CD) derivatives modified by R-configuration groups (R-CPGCD, R-HMPGCD) to silica gel. Nineteen chiral nitro aromatic alcohol derivatives were separated under the polar organic and the reversed phase modes. Better enantioseparation was obtained in the reversed phase mode. The resolution values of the analytes ranged from 1.98 to 7.57 and from 2.19 to 8.14 on R-CPGCD and R-HMPGCD CSPs, respectively, using a mobile phase composed of methanol/water (v/v, 40/60). Better enantioseparation was obtained on R-HMPGCD CSP than on R-CPGCD CSP because of stronger hydrogen bonding and π-π interactions between the substituents on the cyclodextrin derivatives and the analytes. For different analytes, the increasing electronic density of the benzene ring was found to be favorable to the enantioseparation of the test analytes. The thermodynamic parameters showed that the enantioseparation of analytes was enthalpy-controlled and a lower temperature aided the enantiomeric separation of the solutes on the two CSPs. MD simulations were used to investigate the recognition mechanism between the chiral selectors and the analyte using R-, S-2-naphthalenemethanol and R-CPGCD and R-HMPGCD complexes as examples. S-2-naphthalenemethanol had the stronger interactions with R-CPGCD and R-HMPGCD than the R-isomer. The substituent derivatized on R-CPGCD and the cyclodextrin cavity contributed to the discrimination of the S-isomer, but only the derivatized group on R-HMPGCD was found to play a major role in separating prosess. In addition, the larger free energy deviation of the R- and S-isomers in the R-HMPGCD system brought about a higher resolution value (Rs = 8.14).