Electrochemical Investigation of the Redox Behavior of Isoquinoline Alkaloid Emetine

Abstract

Emetine is a biologically active isoquinoline alkaloid with reported antiviral, anticancer, and antiparasitic properties; however, its broader therapeutic application remains limited by dose-dependent toxicity and an incomplete understanding of its oxidative behavior. The electrochemical oxidation of emetine at a glassy carbon electrode (GCE) under physiologically relevant conditions was investigated using cyclic voltammetry (CV), differential pulse voltammetry (DPV), controlled-potential electrolysis (CPE), UV–Vis and fluorescence spectroscopy, and high-resolution LC–QTOF–MS/MS. DPV revealed three irreversible anodic oxidation processes centered near +0.90, +1.01, and +1.25 V versus Ag/AgCl. Scan-rate studies showed that the two lower-potential processes are predominantly diffusion-controlled, whereas the higher-potential process exhibits greater contributions from surface-associated and interfacial phenomena. pH-dependent studies (pH 4.0–9.1) demonstrated that emetine oxidation is strongly influenced by the protonation state and proceeds through a complex multistep irreversible mechanism. CPE generated multiple oxidation products, and subsequent high-resolution LC–QTOF–MS/MS analysis revealed ten emetine-associated products (P1–P10). Tentative structural assignments for P1–P8 encompassed dehydrogenated, oxygenated/dehydrogenated, and nitrogen-containing products, whereas P9 and P10 remained structurally unresolved. Together with complementary spectroscopic evidence, these findings support a mechanistic model in which emetine oxidation is initiated at amine functionalities and adjacent benzylic carbon centers, followed by competing dehydrogenation, oxygen incorporation, and secondary product-forming reactions. This study establishes a mechanistic framework for emetine electrooxidation and demonstrates the utility of integrating electrochemistry with high-resolution mass spectrometry to investigate the oxidative chemistry of bioactive isoquinoline alkaloids.