Engineering Intrinsic Chirality in Pd@AuPd Alloy Nanoparticles: Decoupling Surface Catalytic Activity from Enantioselectivity for Robust Multiplexed Biosensing

Chirality confers unique functionalities to nanomaterials, enabling advances in molecular recognition and asymmetric catalysis. However, the development of electrochemical chiral sensors that simultaneously achieve high catalytic activity, robust enantioselectivity, and stability in complex biological media remains a grand challenge. Most existing systems rely on surface‐adsorbed chiral ligands, which are prone to desorption and instability. In this study, we present a structural engineering strategy to decouple surface electrocatalytic activity from enantiomeric recognition using intrinsically chiral Pd@AuPd alloy nanoparticles. By precisely modulating the surface Pd content, we optimized the electronic structure for high‐sensitivity ascorbic acid (AA) detection (LOD = 300 nM). Critically, ligand‐exchange experiments with achiral 11‐mercaptoundecanesulfonate (MUS) unambiguously confirmed that the enantioselectivity originates from the intrinsic helical distortion of the metal core rather than surface ligands. This “core‐determined chirality, surface‐determined activity” mechanism endows the sensor with exceptional stability and resistance to interference. Furthermore, the platform enables the ultrasensitive, simultaneous quantification of AA, dopamine (DA), and uric acid (UA) in serum. This work establishes a new paradigm for designing intrinsically chiral metallo‐biosensors, overcoming the limitations of ligand‐dependent systems.