Chiral Gold Nanopropellers: Engineering Plasmonic Chirality for Enantioselective Recognition Through Stereoselective Binding

Enantioselective sensing remains a challenge due to the weak chiroptical responses of small molecules and the limited stereospecificity of plasmonic substrates. Here, a dual‐modality platform that integrates plasmonic chirality and molecular recognition is designed and implemented using cysteine‐functionalized chiral gold nanopropellers (CGNPs). The structural chirality of CGNPs creates localized optical hotspots with defined handedness, which are further amplified through the stereoselective binding of chiral ligands. Surface‐enhanced Raman spectroscopy (SERS) reveals reproducible intensity enhancements and band shifts for stereomatched CGNP–analyte combinations. Quantitatively, the chiral discrimination ability (CDA) reaches 36.0%, and the detection limit for L‐phenylalanine is 2.75 µM. Circular dichroism spectroscopy confirms the selective chiral interactions, while density functional theory (DFT) calculations indicate lower binding energy and shorter interaction distances for the L‐CGNP–L‐phenylalanine complex. Finite‐difference time‐domain (FDTD) simulations show that handedness‐matched light and nanopropeller geometry yield stronger near‐field intensities and more radiative plasmonic modes. These combined experimental and theoretical results demonstrate that enantioselectivity arises from the cooperative effect of chiral field localization and stereospecific molecular adsorption. Together, these results establish CGNPs as a versatile platform for enantioselective sensing, integrating chiral plasmonics and molecular recognition for next‐generation analytical technologies.