Constructing high-dispersed Au anchored COFs composites by in-situ self-reduction method for realizing sensitive SERS detection of letrozole

Surface-enhanced Raman spectroscopy (SERS), an ultrasensitive molecular fingerprinting technique, requires substrates that synergistically integrate electromagnetic field amplification (via plasmonic hotspots) and analyte enrichment (through nanoscale molecular confinement). Although metal nanoparticles (NPs) generate hotspots, their practical utility is hindered by chemical instability, poor reproducibility, and weak analyte affinity. Covalent organic frameworks (COFs), with designable porosity, ultrahigh surface areas, and stability, offer a promising platform to address these limitations. By combining COFs with noble metals, the molecular enrichment capability of COFs and the plasmonic effects of metals can be synergistically exploited. However, conventional synthesis strategies (chemical reduction, pre-synthesis anchoring) suffer from complex multi-step processes, reducing agent dependence, and irregular deposition of metal NPs on the COF matrix, which compromise SERS performance. Our study proposed a sulfur-rich COF leveraging Au–S soft acid-base interactions to achieve in situ reduction of Au 3+ to Au 0 within COF matrices. Three synthesis approaches−chemical reduction, physical adsorption, and in-situ reduction−were systematically compared, with the in-situ method demonstrating superior SERS enhancement and reproducibility due to the confinement of large-area and high-density NPs. The optimized COF/Au composite enabled ultrasensitive detection of letrozole at 6.07 × 10 −8  g/mL, leveraging COF-inherent Raman peaks for internal calibration. This work provides an innovative solution for developing next-generation SERS sensors with acceptable sensitivity, anti-interference capability, and reproducibility.