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

Abstract 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 (Δ G ₁ = −29.36 kcal/mol, Δ G ₂ = −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.