Preparation and evaluation of a chiral porous organic cage based chiral stationary phase for enantioseparation in high performance liquid chromatography

Porous organic cages (POCs) are a new kind of porous molecular materials, which have gained widespread interest in many fields due to their intriguing properties, including excellent molecular solubility, inher-ent molecular cavity and rich host-guest chemistry. To date, many chiral POCs have been explored as chiral stationary phases (CSPs) for gas chromatographic (GC) separation of enantiomers. However, the ap-plications of chiral POCs for high performance liquid chromatography (HPLC) enantiomeric separation is extremely rare. In this study, we report the construction of thiol-ene click reaction for the preparation of CSP for HPLC by using a [4 + 8]-type chiral POC NC4-R as chiral selector. The fabricated CSP showed good chiral resolution performance not only in normal-phase HPLC (NP-HPLC) but also in reversed-phase HPLC (RP-HPLC). Seventeen and ten racemates were well resolved in the two separation modes, respectively, including ketones, esters, alcohols, phenols, amines, ethers, organic acids, and amino acids. Moreover, the fabricated column also shows good chiral recognition complementarity to two popular chiral HPLC columns (Chiralpak AD-H and Chiralcel OD-H columns) and previously reported chiral POC NC1-R-based HPLC column, which can resolve some racemates that unable to be resolved by the two commercially available chiral HPLC columns and NC1-R-based column. The relative standard deviation (RSD) values ( n = 4) of retention time and resolution ( Rs ) of analytes separated on the column were less than 0.3 % and 0.5 % after it was subjected to different injections, showing the good reproducibility and stability of the NC4-R-based column. This work demonstrated high potentials of chiral POCs for HPLC enantiosepara-tion and the applicability of chiral POC-based HPLC columns can be broadened by developing more chiral POCs with diverse structures as chiral selector for HPLC.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, a thiol-ene click reaction was used to construct a CSP for HPLC using a [4 + 8]-type chiral POC NC4-R as the chiral selector. The fabricated CSP exhibited good chiral resolution performance in both NP-HPLC and RP-HPLC, and showed excellent reproducibility and stability. This work demonstrated the high potential of chiral POCs for HPLC enantiomeric separation.