[Quantum chemical calculations for elucidating chiral resolution mechanism of chiral covalent organic frameworks 6 chromatographic stationary phase].

With the aim of exploring the chiral resolution mechanism of the chiral covalent organic frameworks 6 (CCOF6) chromatographic stationary phase, the ORCA program was used to optimize the structures of CCOF6 and four pairs of enantiomers. Then the molecular docking of CCOF6 with each enantiomer was performed by AutoDock program to obtain the initial interaction configurations of CCOF6 with four pairs of enantiomers. Energy calculations of the initial configurations were performed by ORCA program (B3LYP functional with DFT-D3 correction, def2-TZVP orbital basis set, def2/J auxiliary basis set, and RIJCOSX used to accelerate the calculation) to determine the interaction configurations of CCOF6 with four pairs of enantiomers and to obtain the corresponding binding free energy and binding free energy difference. Wave function analyses of ORCA calculation results were performed by Multiwfn program, and the weak interactions between CCOF6 and the four pairs of enantiomers were visualized by Visual Molecular Dynamics program. The results showed the following:① for calculating the binding free energies of CCOF6 and the four pairs of enantiomers, the ORCA method with the solvation effect was more accurate than the AutoDock method as well as the ORCA method without the solvation effect; ② the greater the absolute value of the binding free energy difference between the CCOF6 stationary phase and enantiomers, the greater was the selectivity factor of the enantiomers but not the resolution of the enantiomers; ③ the hydroxyl group of S-1-phenyl-1-propanol interacted with the ether bond of CCOF6, but the hydroxyl groups of the other enantiomers all interacted with the carbonyl groups of CCOF6, and the binding force between S-1-phenyl-1-propanol and CCOF6 was the weakest; ④ from the peak time of the enantiomer and its binding free energy with CCOF6, it was confirmed that the elution ability of n-hexane/isopropanol for 1-phenyl-1-propanol was the weakest, followed by the elution ability for 1-phenyl-2-propanol; ⑤ the peak time of S-1-phenyl-1-propanol was longer than that of R-1-phenyl-1-propanol, while for the other enantiomers, the peak time of the R-enantiomers was longer than that of the S-enantiomers.