Multiscale Synergistic SERS Chiral Detection: Gold Nanoclusters-Mediated Enantioselective Molecular Discrimination on the Self-Assembly of Gold Nanoparticles

Surface-enhanced Raman scattering (SERS), despite its high sensitivity in molecular fingerprint detection, typically lacks chiral specificity. Chiral metal nanoclusters (CMNCs) with sub-3 nm cores hold promise for chiral molecular sensing, yet their application in SERS-based chiral recognition remains largely unexplored. In this study, two-dimensional self-assembly of Au nanoparticles (NPs, 30 ∼ 50 nm) functionalized with D- or L-penicillamine (Pen) stabilized sub-3 nm Au nanoclusters (NCs) were constructed as SERS-active substrates. On these substrates, distinct SERS signals were observed for L- versus D-phenylalanine (Phe) enantiomers, with a signal intensity difference of approximately 5-fold at a low concentration of 10–6 mol/L, suggesting a good enantiomeric discrimination effect and detection sensitivity. Similar chiral discrimination phenomena were also found by using propranolol enantiomers or chiral Cu NCs. These findings demonstrate the significant potential of the integration of CMNCs into plasmonic SERS substrates for developing sensitive chiral sensing strategies based on nonchiral vibrational Raman spectroscopy and advancing the fundamental studies of metal nanocluster-molecule chiral interactions.