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

Abstract

The integrative study of the pharmacokinetics and dynamics of a drug has been of great research interest due to its authentic description of the biomedical and clinical pros and cons. Acetaminophen (N-acetyl-4-aminophenol, AcAP) is a well-known analgesic having a high therapeutic value, including the Covid-19 treatment. However, an overdose of the drug (>200 mg/kg of men) can lead to liver toxicity. An intermediate, N-acetyl-p-benzoquinone imine (NAPQI), metabolite formation has been found to be responsible for the toxicity. For the detection of NAPQI, several ex situ techniques based on electrochemical methods followed by nuclear magnetic resonance, high-performance liquid chromatography, and LC-MS were stated. For the first time, we report an in situ electrochemical approach for AcAP oxidation and NAPQI intermediate (M w = 149.1 g mol–1) trapping on a graphitic nanomaterial, carbon black (CB)-modified electrode in pH 7 phosphate buffer solution (CB@NAPQI). The NAPQI-trapped electrode exhibited a surface-confined redox peak at E°′ = 0.350 ± 0.05 V vs Ag/AgCl with a surface excess value of 3.52 n mol cm–2. Physicochemical characterizations by scanning electron microscopy, Raman, FTIR, and in situ electrochemical quartz crystal microbalance (EQCM) techniques supported the entrapment of the molecular species. Furthermore, the scanning electrochemical microscopy (SECM) technique has been adopted for surface-mapping the true active site of the NAPQI-trapped electrode. As a biomimetic study, the mediated oxidation reaction of NADH by CB@NAPQI was demonstrated, and the mechanistic and quantitative aspects were studied using cyclic voltammetry, rotating disc electrode, amperometry, and flow injection analysis techniques.

Electrical Wiring of Malarial Parasite Intermediate Hematin on a Tailored N-Doped Carbon Nanomaterial Surface and Its Bioelectrocatalytic Hydrogen Peroxide Reduction and Sensing

“…Based on the bar chart of surface excess value against various configurations of the chemically modified electrodes, it has been revealed that the N-doped GQD overlaid on the MWCNT provides the best condition for the proper molecular wiring ({hematin-Fe­(axial)---N-GQD}) of the hematin and the electron transfer reaction (Figure E) and its other control CV graphs are provided in Figure S2,A–D. It is plausible that the multiple interactions between hematin and N-GQD mimic the pharmacokinetics and dynamics observed in biological system. , …”

Redox-Active Green Electrode: Plant-Based Betanin Immobilized on Carbon Black for Drift-Free Voltammetric and Potentiometric pH Sensor Applications

“…4B). Based on the following Sauerbrey equation 45,54 as the frequency of the crystal oscillator decreases, the mass value that increases during the electrochemical reaction was continuously monitored…”

“…During the electrochemical reaction, there is a continuous change in the frequency ( f /Hz) of the EQCM-Au/CB spectrometer, denoting the positive addition of mass on the electrode surface (Figure B). Based on the following Sauerbrey equation , as the frequency of the crystal oscillator decreases, the mass value that increases during the electrochemical reaction was continuously monitored normalm ass change , normalΔ m = ( − 1 2 ) f normalo − 2 normalΔ italicfAk ρ 1 / 2 wherein “ f o ” is the oscillation frequency of the EQCM-Au crystal (8 MHz), “Δ f ” is the measured frequency change, “ A ” is the geometric area of the gold quartz crystal (0.196 cm 2 ), “ k ” is the shear modulus of the crystal (2.947 × 10 11 g cm –1 S 2– ), and ρ is the density of the crystal (2.648 g cm –3 ). Based on the equation, Δ m was calculated and plotted against the working potential window as in Figure D.…”

“…Notably, many of these redox probes are susceptible to interference due to mediated oxidation–reduction effects with various chemicals and biochemicals. Table provides a comparative overview of the present pH sensors in comparison to literature reports, including representative information about interference. ,− ,− ,,, Due to the mixed potential mechanism of mediated oxidation/reduction reactions, significant voltage drift is expected, leading to false-positive pH readings. Additionally, many redox probes used for pH monitoring are expensive (IrO 2 and RuO 2 ), toxic (hydroquinone, quinoline, pyrroloquinoline, and catechol), and require additional protection layers like Nafion for interference-free electrochemical pH monitoring .…”