Integrated Chiral Recognition and Enantiomeric Separation of Histidine by Metal–Organic Frameworks Engineered with Chiral Linkers

as the peroxidase-like (POD-like) activity center. MOF-TH-Fe enabled the chiral recognition of histidine enantiomers via dual-mode enantioselective detection. The results indicated that l-His significantly quenched the fluorescence intensity of MOF-TH-Fe at 655 nm, while d-His showed a negligible effect. Alternatively, a colorimetric method was established by exploiting the differential effect of l/d-His on the POD-like activity of MOF-TH-Fe. The fluorescence and colorimetric assays offered detection limits of 0.57 and 1.74 μM, respectively. Molecular simulations explained the mechanism of chiral recognition and revealed the different interactions between chiral linkers and histidine enantiomers. To verify its potential in chiral separation, MOF-TH-Fe was integrated with a fixed-bed continuous flow system to separate the enantiomers of histidine. After 3.5 h of continuous operation, an enantiomeric excess (ee) of 71.69% was achieved. This study successfully established a multifunctional platform integrating chiral recognition, separation, and catalysis, providing design insights for the development of next-generation multifunctional chiral nanomaterials.