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 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 has developed a synthesis method for APAP oxidation products in order to further study the metabolites that may form in the liver. Synthesis methods use both enzymatic and electrochemical means. Analysis by 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.