Biomembrane-Inspired Plasmonic Superstructures with Phenolic-Resin Artificial Pockets for Enantioselective Surface-Enhanced Raman Spectroscopy Detection.

Reliable chiral discrimination of amino acid enantiomers is critical for pharmaceutical development, quality control, and biomarker analysis. Despite the high sensitivity of SERS, enantio-discrimination remains challenging due to near-identical spectra and inefficient analyte localization in plasmonic hotspots. Inspired by biomembrane-pocket recognition that converts multiple interactions into functional outputs, we develop SiO2@Au@RF plasmonic superstructures integrating porous resorcinol-formaldehyde (RF) pocket interface with a programmable three-dimensional (3D) plasmonic amplifier for ligand-free chiral SERS discrimination. The ultrathin RF shell provides nanochannels enriched with phenolic and aromatic motifs, enabling cooperative noncovalent interactions and pronounced differential adsorption kinetics toward molecules with terminal -NH2 and -COOH groups. Confined seed-mediated growth constructs a densely coupled 3D Au hotspot matrix with abundant nanogaps, yielding a 3.8-fold increase in the hotspot number and 2.5-fold higher maximum near-field intensity relative to representative 2D models. As a demonstration, l- and d-tryptophan show pronounced discrimination on the superstructures, and a linear calibration of enantiomeric excess is achieved. Notably, this strategy can be further extended to multiple amino acid pairs with positively charged side chains, including histidine, arginine, and glutamine. This work offers a distinct strategy to ligand-free enantioselective SERS sensing and expands the design space for practical chiral analysis.