Benzyl Chloroformate-Functionalized Fluorescent Silica Nanoparticles for Detection of Norepinephrine

Norepinephrine (NE) plays a critical role in human physiology, and its abnormal levels are linked to diseases like Alzheimer’s and depression. Accurate NE detection in serum is crucial for clinical diagnosis and biomedical research. However, existing methods face challenges in specificity and sensitivity for complex biological samples. To address this, we developed a fluorescent nanosensor based on silica nanoparticles (Si NPs). Using a one-step hydrothermal method, we prepared Si NPs and modified their surface with benzyl chloroformate, creating a silica-based fluorescent nanosensor (CBZ-Si NPs). This design establishes a distinctive chemical microenvironment on the nanoparticle surface, enabling highly specific binding to NE. The sensor demonstrates outstanding sensitivity and selectivity, with fluorescence intensity linearly correlating with NE concentration in the range of 0.05–1.00 μM (R2 = 0.9996) and a detection limit of 2.50 nM. It effectively resists interference from structural analogs like epinephrine and isoproterenol (ISO). Applied to serum samples, CBZ-Si NPs offer reliable NE detection, supporting disease diagnosis with a simple and feasible method. Density functional theory (DFT) analysis reveals that CBZ-Si NPs specifically recognize NE through a six-membered cyclic hydrogen bond, which is a previously unreported interaction model. Structural analogs of NE, due to reduced electron density and reactivity, fail to form strong hydrogen bonds. This study highlights the performance, and practicality of CBZ-Si NPs, providing a promising tool for rapid and accurate NE detection in biological samples for disease diagnosis.