Chirality‐Matching in Au–S Oriented Assembly Induces Highly Selective Recognition of Glucose Enantiomers

ABSTRACT Enantioselective distinction of glucose (Glu) is a core challenge in biochemistry, as its subtle difference in chiral configuration leads to distinct biological activities. To address this, we propose an “Au─S oriented assembly‐chiral matching amplification” strategy, D/L‐cysteine (Cys) serves as a chiral recognition moieties and is immobilized on gold nanoparticles (Au NPs) via Au─S bonds to construct a chiral interface with well‐defined enantioselectivity. Mechanistic studies reveal that the chiral microenvironment of Cys optimizes the orientation and adsorption of Glu on the electrode surface through stereomatching effects, which in turn regulates enantioselective differences in electron transfer efficiency, endowing the interface with excellent enantioselectivity. Specifically, Au‐D‐Cys exhibits a significantly stronger electrochemical response to D‐Glu than to L‐Glu, while Au‐L‐Cys shows the opposite trend. The constructed electrochemical sensor has a linear range of 1–558 m m for both D‐Glu and L‐Glu, with corresponding sensitivities of 19.95 and 12.87 µA m m −1 cm −2 , enabling accurate quantification and distinction. This work demonstrates that chiral configuration matching effectively enhances sensor performance, providing a new strategy for the recognition of multi‐chiral‐center enantiomers.