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 (Mw = 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. © 2023 American Chemical Society.
ABSTRACT
The importance of rapid access to diagnostics tools in the identification of pathogens-including their crucial component, bioreagents-was recently underscored in the COVID-19 pandemic. The currently adopted synthesis of dithiothreitol (DTT) involves four steps in batch with long reaction times and which generates a highly carcinogenic and mutagenic bis-epoxide intermediate. In this work, we have developed an intensified telescoped three-step continuous flow synthesis of DTT involving a base-mediated ring closure epoxidation, a nucleophilic epoxide opening with thioacetic acid, and an acid-mediated deacetylation. One of the key features is that the first two steps are conducted in a telescoped continuous flow fashion, allowing generation and consumption of the hazardous intermediate in situ, suppressing the need for its isolation, and improving the overall safety of the synthesis. The process is completed by an acid-catalyzed deacetylation and a subsequent recrystallization to afford the desired DTT. Flow chemistry allows here to intensify the process by using high temperatures and high pressures while minimizing the number of unit operations and improving the overall safety of the process. Our protocol permits the on-demand production of DTT in case of future outbreaks. © 2023 American Chemical Society.