Catalyst-Free Synthesis of Thiourea-Linked Dumbbell-Shaped POSS for Ultrasensitive Determination of Prilocaine in Human Blood with Computational Insights

Abstract

Although various electrochemical sensors have been reported for the determination of local anesthetic drugs, most existing platforms suffer from limited sensitivity, insufficient surface stability, or inadequate electron-transfer efficiency, particularly when applied to complex biological matrices. Moreover, the potential of hybrid polyhedral oligomeric silsesquioxane (POSS)-based nanostructures combined with metal oxide nanoparticles for improving electroanalytical performance has not yet been thoroughly explored. In this study, a high-sensitivity electrochemical nanosensor was developed for the determination of prilocaine (PC), an amide-type local anesthetic, using a glassy carbon (GC) electrode modified with POSS‑titanium dioxide (TiO<inf>2</inf>) nanoparticles (Nps). The combination of modifications provided a unique electrode surface by combining the high stability of POSS with the strong adsorption properties of TiO<inf>2</inf> Nps, thereby increasing both surface loading and adsorption capacity. To elucidate the structure of the modification combination, 1H and 13C nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopic techniques, as well as Brunauer–Emmett–Teller (BET), X-Ray diffraction (XRD), Electrochemical impedance spectroscopy (EIS), and high-resolution transmission electron microscopy (HRTEM) analysis techniques were used, respectively. The analytical performance of the developed nanosensor was systematically optimized using differential pulse voltammetry (DPV), adsorptive stripping differential pulse voltammetry (AdSDPV), square wave voltammetry (SWV), and adsorptive stripping square wave voltammetry (AdSSWV) techniques. As a result of the optimization studies, the lowest limit of detection (LOD) was 3.66 × 10−8 M with the AdSSWV technique. DFT results corroborated the mechanism, indicating ring-centered electron donation (HOMO) and adsorption-favored N/O regions (MEP). Low LOD values were also recorded with other techniques, demonstrating the method's high sensitivity in analyte detection. In real sample analysis tests, PC recovery value in human blood samples was determined to be 98.69% using the AdSDPV technique. Despite the matrix effect, the nanosensor demonstrated high accuracy and reproducibility. The results indicate that the developed POSS-TiO<inf>2</inf> Nps modified GC electrode sensor offers a high-performance, reliable, and good electrochemical detection platform suitable for use in biological and clinical applications. © 2024