Journal of Photochemistry and Photobiology A: Chemistry 135 (2000) 171–177 Chemical and photochemical oxidation of tetrahydrobetacarboline C. Carmona ∗ , R. Ghanem, M. Balón, M.A. Muñoz, P. Guardado Departamento de Qu´ ımica F´ ısica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain Received 7 February 2000; accepted 16 April 2000 Abstract The photophysics and the mechanisms of the photochemical and chemical aromatization of 1,2,3,4-tetrahydro-7H-pyrido/3,4-b/indole (THBC) in 40% v/v methanol–water media have been investigated. The primary photophysical processes of THBC resemble those of indoles and related alkaloids. The photochemical oxidation has been carried out in the presence of atmospheric oxygen and light. The chemical oxidation has been studied using sodium peroxodisulphate (PDS) as the electrophilic agent. In both cases, strong acid media, i.e., sulphuric acid concentrations higher than 0.5 mol dm −3 are needed for the dehydroderivative (DH) to be formed. In the photochemical oxidation, the rate constants for the disappearance of THBC increase linearly with the concentration of acid and the intensity of the exciting radiation. However, the formation of DH only depends on the acidity of the media. In the chemical oxidation a similar behaviour is observed. In this case, the rate constants for the disappearance of THBC increase linearly with both PDS and acid concentrations, and the appearance of DH solely varies with the acid concentration. A two step mechanism is proposed for these oxidation reactions. In the first step, excited or ground state THBC reacts with ground state oxygen or PDS, respectively, to give an indolenine intermediate. This intermediate slowly rearranges, in a second acid catalysed step to yield DH. © 2000 Elsevier Science S.A. All rights reserved. Keywords: Tetrahydronorharmane; Photophysics; Oxidation; Kinetics 1. Introduction The tetrahydrobetacarboline ring, 1,2,3,4-tetrahydro-7H- pyrido/3,4-b/indole (THBC) constitutes the basic element of numerous natural indolic alkaloids such as those belonging to the Harmala or Rauwolfia families [1–4]. These alkaloids occur in some plants like Peganum Harmala, Rauwolfia Ser- pentine, and in various marine organisms [5–7]. Several tetrahydrobetacarbolines are endogenous, albeit trace, constituents of the mammalian brain [8–10]. These so-called mammalian THBC alkaloids probably arise en- dogenously from the condensation of central nervous system indolamines (or their precursor amino acid L-tryptophan) with an aldehyde or -keto acid via Pictet–Spengler reaction [11]. Other THBCs also appear to be formed after ingestion of ethanol [12], and the hypothesis that these alkaloids con- tribute to the behavioural changes, physical dependence and addictive properties of ethanol has been advanced. Although the mammalian metabolism of THBCs has not been stud- ied, the fact that their oxidation reactions do occur in vivo might be implied from the observation that these alkaloids and their aromatized derivatives are present in human urine after alcohol consumption [12]. Also, THBCs are thought to ∗ Corresponding author. E-mail address: carmona@fafar.us.es (C. Carmona) be oxidized to a reactive intermediate which can cross-link proteins in aging human lenses suggesting that they might be involved in cellular aging phenomena [13]. In spite of the interest of the oxidation chemistry of THBCs, there have been no systematic studies on these reactions. However, it appears to be rather widely believed [14] that oxidation of these alkaloids should ultimately result in the formation of their partial or totally aroma- tized derivatives. For this reason, in this report we have studied the aromatization reactions of THBC, the most rep- resentative member of the tetrahydrobetacarboline’s family. Because this alkaloid can be chemically and photochemi- cally oxidized, we have analysed both oxidation processes and the factors that favour the aromatization reactions. The photochemical study has been carried out in the presence of atmospheric oxygen and light, while for the chemical study the oxidizing agent, sodium peroxodisulphate (PDS), has been used. 2. Experimental 2.1. Reagents THBC was purchased from Sigma-Aldrich Qu´ ımica and was used as received. Stock solutions of the substrate, 1010-6030/00/$ – see front matter © 2000 Elsevier Science S.A. All rights reserved. PII:S1010-6030(00)00294-X