Enantioselective dispersive solid-phase extraction of chiral drugs and amino acids using a homochiral Zn-based MOF: Mechanistic insights into chiral recognition

A chiral metal-organic framework, [Zn( NCG )bpy] n (NCG = N-(4-aminobenzoyl)- L-glutamic acid; bpy = 4,4′-bipyridine), was meticulously designed and synthesized for the first time and thoroughly assessed for its extensive chiral recognition abilities. This MOF features an average pore size of 7.12 nm and is constructed from enantiopure N-(4-aminobenzoyl)-L-glutamic acid ligands, which provide functional sites for the highly enantioselective adsorption and separation of various chiral compounds. The chiral recognition ability of [Zn( NCG )bpy] n was initially tested with batch adsorption of ( R )- and ( S )-dropropizine enantiomers at various starting concentrations and solution pH levels. A dispersive solid-phase extraction (dSPE) strategy coupled with high-performance liquid chromatography (HPLC) was then employed to assess its competitive chiral resolution efficacy toward four structurally distinct racemates: ( R , S )-dropropizine, ( R , S )-tetramisole hydrochloride, (D,L)-phenylalanine, and (D,L)-aspartic acid. The [Zn( NCG )bpy] n exhibited remarkable enantioseparation capability toward smaller amino acid molecules, with an enantiomeric excess ( ee ) of 46.17 ± 1.39% and a separation factor of 2.72 ± 0.10 for (D,L)-phenylalanine in a single batch separation. X-ray photoelectron spectroscopy (XPS), combined with the Independent Gradient Model based on Hirshfeld partition (IGMH) isosurface analysis and binding energy computations, elucidated the underlying recognition mechanism at the atomic level. The results conclusively showed that chiral resolution is primarily regulated by non-covalent host-guest interactions.