Tunable oxidative release of N-acetyl-p-benzoquinone-imine and acetamide from electrochemically derived sub-monolayer acetaminophen modified glassy carbon electrode

In Situ Electrochemical Trapping and Unraveling the Mechanism of the Toxic Intermediate Metabolite N-Acetyl-p-Benzoquinone Imine of the Acetaminophen Drug and Its Biomimetic Mediated NADH Oxidation Reaction

“…The AcAP→NAPQI formation mechanism, in the literature, following three different routes was proposed: (i) cytochrome P450-assisted N -hydroxylation followed by a water removal reaction, (ii) one-electron oxidation of the phenolic site of AcAP followed by molecular rearrangement to NAPQI, , and (iii) direct two-electron/proton-coupled electron transfer reaction from AcAP to NAPQI ,,,, (Scheme ). Indeed, there is no direct evidence for the molecular transformation reaction of AcAP to NAPQI so far.…”

“…Complexity in the pharmaceutical reaction, isolation, instability, and an inadequate characterization tool for the identification of NAPQI/NAPSQI intermediates are the major limitations. Previously, a glassy carbon electrode (GCE)-based homemade detector coupled with a high-performance liquid chromatographic technique (HPLC), ellipsometry, nuclear magnetic resonance (NMR), , ESI-MS, and radio labeling-based , analytical methods have been used for the ex situ analysis of NAPQI, wherein electrochemically synthesized products were separated and subjected to the respective analysis. Meanwhile, there are few literature reports which speculated various intermediates of AcAP without any characterization support. − Table summarizes some of the literature for the NAPQI formation and its confirmation by various techniques. − Although the above-mentioned methods showed a quantitative detail of the intermediate, it cannot provide real-time qualitative information of the true active species, which calls for the use of an in situ /operando technique.…”

“…Complexity in the pharmaceutical reaction, isolation, instability, and an inadequate characterization tool for the identification of NAPQI/NAPSQI intermediates are the major limitations. Previously, a glassy carbon electrode (GCE)-based homemade detector coupled with a highperformance liquid chromatographic technique (HPLC), 3 ellipsometry, 14 nuclear magnetic resonance (NMR), 15,16 ESI-MS, 17 and radio labeling-based 4,18 analytical methods have been used for the ex situ analysis of NAPQI, wherein electrochemically synthesized products were separated and subjected to the respective analysis. Meanwhile, there are few literature reports which speculated various intermediates of AcAP without any characterization support.…”