Decoding Proton‐Coupled Electron Transfer Mechanism of Nicotine for Multi‐Scenario Portable Electrochemical Sensing

A key challenge in nicotine electroanalysis is the unresolved complexity of its interface process, which directly determines sensor metrics. We have developed a screen-printed analysis strip to elucidate potential proton-coupled electron transfer processes, while achieving multi-scenario nicotine detection (tobacco leaves, dry tobacco leaves, cigarettes, and smokers' saliva). The electrochemical characterization of elucidated the pH-dependent (pH 5-9) 2H⁺/2e^- coupling transfer mechanism of nicotine. Density functional theory calculations revealed molecular-level insights: Electrostatic potential and Fukui function revealed the differences in electronic structure characteristics of nicotine molecule in different protonated states and their regulatory in the electrooxidation process; Quantitative characterization of spontaneous protonation thermodynamics (ΔG₁ = -29.36 kcal/mol, ΔG₂ = -17.68 kcal/mol) and interfacial electron transfer (0.0219 e^-) provided theoretical foundations for reaction kinetics; Transition state analysis uncovered a hydroxyl-dominated multilevel synergistic electrooxidation mechanism. This integrated platform not only decodes the complex interface mechanism of nicotine but also establishes a universal research paradigm for proton-coupled systems, demonstrating successful applications from industrial quality control to biomedical monitoring.