Interfacial chemistry governs SERS detectability of trimethoprim and ketoprofen: adsorption geometry and chloride-mediated activation

Pharmaceutical residues such as trimethoprim (TMP) and ketoprofen (KTP) are of growing environmental concern due to their persistence in wastewater and potential ecological impacts. In this study, we developed and evaluated electrochemically synthesized silver nanoparticles (e-AgNPs) immobilized on aluminum substrates as surface-enhanced Raman scattering (SERS) sensors for the detection of TMP and KTP. Structural and morphological characterization confirmed uniform, crystalline nanoparticles with an optimal size (∼50 nm) for plasmonic enhancement. Electrochemical measurements showed that TMP and KTP possess nearly identical LUMO levels, yet their SERS responses differed markedly. TMP exhibited strong and reproducible SERS bands, enabling direct quantitative detection over a wide linear range (10^-4 M to 10^-8 M) with a detection limit of 3.84 × 10^-9 M. In contrast, KTP showed intrinsically weak signals due to unfavorable adsorption geometry. Chloride modification (10^-4 M NaCl) effectively "activated" KTP detectability by displacing citrate ligands and forming Ag-Cl _<i>x</i> ^- surface states, which facilitated the adsorption and charge transfer of the substrate. Under optimized conditions, KTP was quantified over 10^-4 M to 10^-7 M with a detection limit of 2.69 × 10^-8 M. Real-sample validation demonstrated reliable recoveries of TMP (89-96%) and KTP (88-95%) in spiked tap water and commercial pharmaceutical tablets, despite matrix interferences. These obtained results highlight the decisive role of adsorption chemistry in SERS detectability and demonstrate that interfacial modification with chloride can extend SERS applicability to weakly adsorbing pharmaceutical pollutants, offering a sensitive platform for environmental monitoring and pharmaceutical quality control.