“Click” post-synthesis of chiral microporous organic network for chiral high-performance liquid chromatographic separation

Abstract

Background

Chiral separation is of great significance but remains challenging in analytical chemistry. Chiral stationary phase based high-performance liquid chromatography (HPLC) is regarded as one of the most effective and widely used methods for chiral resolution. Microporous organic networks (MONs) are an emerging class of porous materials with designable topology, large surface area, abundant micropores, and excellent stabilities that have attracted tremendous interests in chromatographic separation. However, the usage of chiral MONs as chiral stationary phases for chiral HPLC separation has not been reported so far.

Results

Herein, we present the first example of chiral MON@SiO₂-L-Cys as a novel stationary phase for chiral HPLC. MON@SiO₂-L-Cys is post-synthesized with l-cysteine (L-Cys) via the specific thiol-yne click reaction. The packed MON@SiO₂-L-Cys column is able to separate chiral aromatic alcohols, esters, and nitriles with good resolution (4.00 for 2-phenyl-2-pentanol) and high selectivity (3.56 for propranolol hydrochloride). Effects of sample dosage, mobile phase composition, and separation temperature are studied. The MON@SiO₂-L-Cys packed column also exhibits chiral recognition complementarity with three commercial chiral columns. For example, 2-amino-2-phenylethanol and propranolol hydrochloride are able to achieve baseline separation on MON@SiO₂-L-Cys packed column, but cannot be separated on commercial Chiralpak IA, IB, and IH columns. In addition, the MON@SiO₂-L-Cys packed column gives comparable separation performance for 2-phenyl-2-pentanol even after 9 months’ utilization.

Significance

This work reports the first example of constructing chiral MON-based stationary phase for chiral HPLC separation via the facile click post-synthesis strategy. This study demonstrates the considerable prospect of chiral MONs as efficient chiral stationary phases for chiral HPLC and may open up a new area of MONs in chiral separation.