Spring 2022 National ACS Abstract

Synthesis and Characterization of Acetaminophen Oxidation Products

Matthew W. Simonson and Bradley E. Sturgeon Monmouth College, Department of Chemistry

Acetaminophen (APAP) is a common analgesic and an active ingredient in many painkillers such as Tylenol and Percocet. Upon overdose, APAP misuse can lead to toxicity in the liver, which accounts for a striking proportion of acute liver failures in the United States annually. Considering the potential for APAP induced hepatotoxicity, our research group developed a synthesis method for APAP oxidation products in order to further study the potential metabolites that form in the liver during APAP overdose. Synthesis methods were explored using oxidation mechanisms of both enzymatic oxidation and bulk electrolysis. Analysis of both reactions by high performance liquid chromatography (HPLC) indicates the oxidation of APAP results in the same product outcome, yet electrochemical oxidation yields a more controlled product selection. Further characterization of these APAP oxidation products were carried out using electron spin resonance (ESR), quadruple time-of-flight mass spectrometry (qTOF-MS), and cyclic voltammetry (CV). Our findings purport that APAP prefers to oxidize through a mechanism of radical polymerization, which lends insight into the oxidation cascade that occurs as the liver oxidizes APAP during times of overdose. Furthermore, the synthesis of four APAP oxidation products in high yield has important implications in understanding their potential biological activity.