Electrochemistry of Selected Acetaminophen Derivatives

Abstract

Acetaminophen (N-(4-hydroxyphenyl)acetamide, APAP) belongs to the most frequently used pharmaceuticals with analgesic and antipyretic effect [1]. The metabolization of APAP via oxidation pathway lead to formation of highly reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI). It immediately reacts with a nucleophile e.g. with glutathione by formation of respective conjugate. The level of such conjugates can be directly linked to the toxicity of APAP in humans.Hence, three derivatives of acetaminophen were synthesized and characterized [2]. In this contribution, we focus on the characterization of redox properties of selected acetaminophen derivatives (see scheme 1) which were studied by means of cyclic voltammetry, rotating-disk voltammetry and UV-VIS absorption spectrometry. The oxidation mechanism was studied in phosphate buffers of different pH as well as in non-aqueous environment of N,N-dimethylformamide The influence of substituents on the electron transfer mechanism was estimated and corresponding rate constants were evaluated. We found that the protonation/deprotonation of acetaminophen derivatives act as a rate determining steps in aqueous media. The obtained electrochemical results were accompanied by chemical ones using reaction of the conjugates with diphenylpicrylhydrazyl (DPPH radical assay) in order to examine their interaction with radical, hence radical scavenging ability. Acknowledgement This work was supported by the Czech Science Foundation (GA19-11867S). References L. O. Boreus, F. Sandberg, Acta physiologica Scandinavica 1953, 28, 261-265.J. Vanova, D. Malinak, R. Andrys, M. Kubat, T. Mikysek, E. Rousarova, K. Musilek, T. Rousar, P. Cesla, J. Chromatogr. A 2022, 1669, 11. Figure 1