High-performance fentanyl molecularly imprinted electrochemical sensing platform designed through molecular simulations

Fentanyl and its derivatives are a type of potent opioid analgesics, with the characteristics of diverse structure, high toxicity, extremely low content, and high fatality rate. Currently, they have become one of the most serious problems in international drug abuse control due to their extensive use in drug production and use. Therefore, the development of a rapid, sensitive, and accurate method for detecting trace fentanyl is of great significance. In this study, in view of its complex structure and trace concentration, a new molecular imprinting electrochemical sensor was developed through molecular simulations followed by experimental validation to detect trace fentanyl. The process consisted of first obtaining the optimal functional monomer and its molar ratio through molecular simulations. The recognition sites of fentanyl-imprinted polymers were predicted to guide the synthesis of imprinted membranes with precision approach to ensure an efficient and accurate reaction process. Reduced graphene oxide (ErGO) was then deposited on glassy carbon electrode surface by electrochemical reduction to yield large numbers of active sites suitable for catalyzing reactions of fentanyl piperidine for promoted efficient electron transfer and amplified sensitivity of the sensor. Accordingly, fentanyl molecularly imprinted film was formed through one-step electropolymerization to yield greatly improved sensing selectivity due to the specific recognition of molecularly imprinted polymer. Under optimal experimental conditions, the fentanyl sensor showed an extended detection range of 3.84×10-9 mol L-1 ∼ 1.72×10-6 mol L-1 and a detection limit of 1.28×10-9 mol L-1. A distinctive feature of this sensor is its molecularly imprinted polymerized membrane, which offers excellent specific recognition, thereby boosting the sensor's selectivity. Throughout the sensor's development process, molecular simulations were employed to steer the synthesis of molecularly imprinted polymers and predict the recognition sites of fentanyl-imprinted polymers. The experimental outcomes proved to align with the simulation data. The final sensor exhibited outstanding selectivity, repeatability, stability, and high sensitivity. The sensor was effectively used to reliably track fentanyl in human serum samples, with acceptable analytical reliability, suggesting its potential for practical applications.