Multidentate 6-Thioguanine-Functionalized Nanoreactors with Hot-Spot-Rich toward SERS Enantiodiscrimination

Abstract Surface-enhanced Raman scattering (SERS) has garnered considerable attention for chiral sensing owing to its high sensitivity to intermolecular interactions. However, achieving high enantioselectivity is still challenging, primarily due to the scarcity of effective molecular recognition elements and optimized SERS platforms. Herein, we report a SERS nanoreactor constructed from phenol formaldehyde resin microporous spheres embedded with densely packed gold nanoparticles (Au@HPFS), which collectively generate abundant and uniformly distributed SERS hotspots. This unique architecture ensures a high enhancement factor and excellent signal reproducibility. Crucially, this nanoreactor is functionalized with 6-thioguanine (6 TG), which serves as a novel multidentate receptor. The receptor specifically captures chiral target molecules through multiple active sites and precisely confines them within the electromagnetic hot spot regions of the nanoreactor. The synergy between the hotspot-rich nanoreactor and the selective receptor enables the highly enantioselective discrimination of eight chiral amino acids and their ester derivatives. Density functional theory (DFT) calculations indicated that the enantioselective SERS spectral behavior may be attributed to multiple hydrogen bond-induced electronic redistribution within the purine ring of the 6 TG receptor complex. This work not only provides a robust SERS strategy for chiral analysis but also offers critical insights into the design of advanced multidentate recognition systems and high-performance SERS nanoreactors, thereby advancing the field of enantioselective sensing.