Pathways of Electrochemical Oxidation of Indolic Compounds Teodor Adrian Enache, Ana Maria Oliveira-Brett* Departamento de Quíımica, Faculdade de CiÞncias e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal tel/fAX: + 351-239-835295 *e-mail: brett@ci.uc.pt Received: November 8, 2010; & Accepted: March 11, 2011 Abstract The electrochemical behaviour of indole and a group of indole-containing compounds with a substituent at the C3 position, indol-3-acetamide (IAM), tryptamine, gramine, indole acetic acid (IAA), indole propionic acid (IPA), indole butyric acid (IBA) and tryptophan, was investigated at a glassy carbon electrode, in order to determine their oxidation pathways. Indole undergoes one irreversible pH dependent oxidation, whereas the oxidation process of indole derivatives was more complex, a two step, the oxidation at C2 position on the pyrrole ring followed by the hydroxylation at the C7 position of the benzene moiety of indoles, irreversible pH dependent oxidation. Keywords: Indole, Indole derivatives, Oxidation, Voltammetry, Glassy carbon DOI: 10.1002/elan.201000671 1 Introduction Indole is an aromatic heterocyclic organic compound with a bicyclic structure, consisting of a benzene ring and a pyrrole ring that occurs predominantly in naturally con- taining compounds such as various plants alkaloids and fungal metabolites [1]. Indole derivatives also play a critical role in microbiol- ogy and clinical diagnostics. Pharmacological studies of indolic compounds reported a wide variety of important biological properties such as anti-inflammatory [2, 3], an- algesic [3], antibacterial [4], antifungal [5], neuroprotec- tive [6, 7], antitumour [8–10] and antioxidant properties [11]. Indole undergoes electrophilic substitution, mainly at C3 position. Substituted indoles are structural elements of the tryptophan-derived tryptamine alkaloids such as the neurotransmitter serotonin, and melatonin, and synthetic precursors of some compounds. Investigations of the redox behaviour of biologically occurring compounds by means of electrochemical tech- niques have the potential for providing valuable insights into the biological redox reactions of these molecules. Due to their high sensitivity, voltammetric methods have been successfully used to study the redox behaviour of various biological compounds. The oxidation behaviour of indole derivatives has al- ready been reported at different electrodes: glassy carbon [12–14], pyrolytic carbon [15–17], carbon paste [18], gold [14], platinum [19], lead dioxide [20] or boron doped dia- mond [21]. Although several pathways regarding the oxi- dation of indole and indole derivatives were already pro- posed, more work needs to be done to fully characterize the electrochemical oxidation mechanisms of these com- pounds. More than 20 different products were reported after HPLC analysis of indole acetic acid in the electrolyzed solution using a pyrolytic graphite working electrode [15, 16]. Two oxidation peaks were found for indole acetic acid using glassy carbon [12], the first oxidation peak being correlated with the oxidation of the C3 of indole. Oxidation at C2 and formation of 2-oxindolalanine after the first oxidation step of tryptophan and its derivatives was also described [14]. The products of the electrochemical oxidation of the carboxylic acid group using a pyrolytic graphite electrode in neutral aqueous medium were characterized as dioxin- dole species and C C-linked dimers by using GS-MS, IR and NMR [17] and the electro-hydroxylation of benzene moiety of the indole molecule by electrochemical oxida- tion and the formation of quinone species was reported [18, 22]. Electrolysis of indole and indole derivatives in non-aqueous solvents (LiClO 4 CH 3 CN, CH 2 Cl) or in aqueous acid solution (HCl, HClO 4 ) can lead to polymer- isation [15, 23–25]. The objective of this work is to investigate and clarify the redox reactions of indole derivatives with a substitu- ent at C3, indol-3-acetamide (IAM), tryptamine, gramine, indole acetic acid (IAA), indole propionic acid (IPA), indole butyric acid (IBA) and tryptophan, using differen- tial pulse and square wave voltammetry at a glassy carbon electrode, in order to clarify the electrochemical oxidation mechanism of naturally or synthetic occurring indoles. Among indole derivatives with a substituent at C3 in- vestigated, only electrochemical studies for IAA and Electroanalysis 2011, 23, No. &,1–8  2011 Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim &1& These are not the final page numbers! ÞÞ Full Paper