Highly Stable Zr(IV)-Based Metal–Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography

Separation of racemic mixtures is
of great importance and interest
in chemistry and pharmacology. Porous materials including metal–organic
frameworks (MOFs) have been widely explored as chiral stationary phases
(CSPs) in chiral resolution. However, it remains a challenge to develop
new CSPs for reversed-phase high-performance liquid chromatography
(RP-HPLC), which is the most popular chromatographic mode and accounts
for over 90% of all separations. Here we demonstrated for the first
time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC.
By elaborately designing and synthesizing three tetracarboxylate ligands
of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three
chiral porous Zr­(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological
structure but channels of different sizes and display excellent tolerance
to water, acid, and base. Chiral crown ether moieties are periodically
aligned within the framework channels, allowing for stereoselective
recognition of guest molecules via supramolecular interactions. Under
acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide
high resolution, selectivity, and durability for the separation of
a variety of model racemates, including unprotected and protected
amino acids and N-containing drugs, which are comparable to or even
superior to several commercial chiral columns for HPLC separation.
DFT calculations suggest that the Zr-MOF provides a confined microenvironment
for chiral crown ethers that dictates the separation selectivity.