Electrochimica Acta 60 (2012) 230–238 Contents lists available at SciVerse ScienceDirect Electrochimica Acta j ourna l ho me pag e: www.elsevier.com/locate/electacta Cyclic voltammetry, spectroelectrochemistry and electron spin resonance as combined tools to study thymoquinone in aprotic medium Rita Petrucci a,∗ , Giancarlo Marrosu a , Paola Astolfi b , Giulio Lupidi c , Lucedio Greci b a Dipartimento di Scienze di Base e Applicate per l’Ingegneria SBAI, Sapienza Università di Roma, Via del Castro Laurenziano 7, I-00161, Rome, Italy b Dipartimento di Scienze ed Ingegneria della Materia, dell’Ambiente ed Urbanistica SIMAU, Università Politecnica delle Marche, Via Brecce Bianche, I-60131, Ancona, Italy c Scuola di Bioscienze e Biotecnologie, Università di Camerino, Via Gentile III da Varano, I-62032, Camerino, Italy a r t i c l e i n f o Article history: Received 19 July 2011 Received in revised form 10 November 2011 Accepted 11 November 2011 Available online 22 November 2011 Keywords: Thymoquinone Superoxide Cyclic voltammetry Spectroelectrochemistry ESR a b s t r a c t Nigella sativa has been used for centuries as a natural remedy for a number of chronic and age-related dis- eases. Thymoquinone (TQ), the main constituent of its extracts, has recently received particular attention and has been tested for its antioxidant, anti-inflammatory and anticancer properties. To further investigate the mechanisms involved in the biological activities of this natural quinone and, among these, in its antioxidant properties, the redox-system of TQ and its interaction with superoxide was studied in aprotic medium by cyclic voltammetry, spectroelectrochemistry and Electron Spin Resonance (ESR). The electrochemical behavior of dithymoquinone (DTQ), the photodimer of TQ, was also studied in the same medium. Experimental data evidenced the formation of the radical anion TQ •- by cathodic reduction of TQ at potential values very close to coenzymes Q ones, by electron transfer (ET) between TQ and superoxide, as KO 2 or electrogenerated, by chemical comproportionation between TQ and the dianion TQ -- and by fast cleavage of the electrogenerated radical anion DTQ •- . Spectroelectrochemical data evidenced that TQ •- , in the presence of TQ, evolves to the hydroquinone monoanion TQH - , suggesting that an H-atom transfer (HT) may occur, likely from the isopropylic side- chain of TQ to TQ •- The H-atom donating ability of TQ may be also supported by Bond Dissociation Energy values and ESR data. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction The seeds of Nigella Sativa L. (Ranuncolaceae), commonly known as black cumin seeds, are primarily used as a spice and food preservative, and have been used in the traditional Arab herbal medicine since ancient time for the treatment of many diseases [1]. In particular, oil extracts have shown immunopotentiation [2,3], antihistaminic [4,5], antidiabetic [6,7], anti-hypertensive [8], anti-inflammatory [9–11], antimicrobial [12,13] and antitumor activity [1,14]. The biological activity of black cumin seeds has been ascribed to the components of the essential oil [11], whose main constituent is thymoquinone (TQ) (38/40%); other constituents of the volatile oil, chemically related to TQ, are thymol (TOH) and thymoquinone dimer (DTQ) called dithymoquinone [15]; only low concentrations of dihydrothymoquinone (TQH 2 ) were found in the oil. TQ was intensively studied and ascribed to possess anti- inflammatory properties [16,17], to decrease the nephrotoxicity of some chemotherapeutic agents [18] and to have inhibitory effects ∗ Corresponding author. Tel.: +39 06 49766855; fax: +39 06 49766749. E-mail address: rita.petrucci@uniroma1.it (R. Petrucci). specific to cancer cells, while it seems minimally toxic to normal cells [1,19–23]. TQ is a very good antioxidant [24] in its oxidized form and, like coenzymes Q, in the reduced form [25]. It has been recently reported [26] that under physiological conditions TQ reacts with GSH, NADH and NADPH to give reduced compounds with even higher antioxidant properties and highly reactive towards differ- ent redox states of hemoglobin and myoglobin [27]. It has also been reported that TQ has a protective effect against gastric lesions which may be related to the conservation of the gastric mucosal redox state [28]. All these biological activities of TQ may be mainly due to its free radical scavenging ability; in particular it has been demonstrated that TQ may act as a strong superoxide anion scavenger or that efficiently inhibits iron-induced lipids peroxidation [29]. At present, the mechanisms involved in the antioxidant activity of TQ are not yet fully understood so that further investigation is necessary to assess its therapeutic value. In this work, the electrochemical behavior of TQ was studied in aprotic medium, in the absence and in the presence of dioxy- gen, by cyclic voltammetry and controlled potential electrolysis in a modified UV cell. The interaction with potassium superoxide 0013-4686/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.electacta.2011.11.055