Enantioselective Surface-Enhanced Raman Scattering Enabled by a Biomimetic Metal−Organic Framework with Catechol Oxidase-Like Activity

Distinguishing chiral compounds remains a major challenge in pharmaceutical development, environmental monitoring, and food safety, largely because conventional optical detection methods suffer from weak signals and insufficient sensitivity. Surface-enhanced Raman scattering (SERS) has emerged as a powerful tool for enantiomeric discrimination, with broad applicability ranging from small chiral molecules to large biomacromolecules. Inspired by natural enzymatic systems, we constructed a biomimetic chiral microenvironment within a zirconium-based metal-organic framework (MOF-808) via post-synthetic incorporation of a copper center chelated with l-histidine (l-His) into its porous architecture. The resulting hybrid material, denoted L-MOF-808-Cu, exhibits catechol oxidase-like activity, in which a Cu(II)/Cu(I) redox cycle drives the oxidation of catechol substrates while concurrently reducing molecular oxygen to hydrogen peroxide (H2O2) under mild conditions. The in situ generated H2O2 was subsequently utilized to oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) into Raman-active oxidized TMB (oxTMB), while L-MOF-808-Cu simultaneously functions as the SERS substrate, amplifying the oxTMB signal. This integrated design enabled enantioselective recognition and quantitative detection of phenolic enantiomers. Using l/d-DOPA as model analytes, enantiomeric discrimination was evaluated directly by monitoring the characteristic oxTMB SERS intensity at 1605.8 cm−1. This biomimetic cascade SERS platform provides a versatile and attractive approach for the sensitive detection and differentiation of chiral molecules.