The effect of metal ions on the electrochemistry of the furazolidone Lida Fotouhi * , Elham Kohestanian, Majid M. Heravi Department of Chemistry, Faculty of Science, Alzahra University, Vanak, P.O. Box 1993891167, Tehran, Iran Received 2 January 2006; received in revised form 1 February 2006; accepted 1 February 2006 Available online 28 February 2006 Abstract A study of the complexing properties of the furazolidone (Fu) with cadmium, copper, nickel, zinc and cobalt was performed in dimethylformamide (DMF) using cyclic voltammetry (CV) and differential pulse (DP) methods with glassy carbon (GC) and dropping mercury electrode (DME). The applied methods allow one to distinguish between the free drugs, free metal ions and their complexes as well as provide evidence that different forms of complexation exist. In aprotic DMF medium, the four electrons reductive peak of the nitro group (NO 2 ) to hydroxylamine (RNHOH) was changed to a one electron reversible peak corresponding to RNO  2 and to a sub- sequent more negative three electrons irreversible peak due to RNHOH. The one electron reduction of Fu to the nitro radical anion RNO  2 is slightly shifted to positive potentials upon addition of Cd(II), Ni(II), Zn(II), Cu(II) and Co(II) and is consistent with the formation of complexes involving the nitro group and the oxygen of the adja- cent furan of Fu. The redox potential of the hydroxylamine in Fu was also shifted to a more positive potential in the presence of metal ions, but their currents decreased. The complexation at different mole ratios was also investigated. The results suggest that in vivo, metal ions, such as Cd(II), Ni(II), Zn(II), Cu(II) and Co(II) facilitate the initial reduction of Fu by capturing the RNO  2 after Fu is reduced by biological reductants. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Furazolidone; Cyclic voltammetry; Metal ions; Complex; Nitro radical anion 1. Introduction Furazolidone and other nitrofuran derivatives have been used for more than 30 years in medicine for the treatment of gastrointestinal infections in animals and humans. The main pharmaceutical uses of nitro aromatic compounds (RNO 2 ) are as antibacterial and anticancer agents [1]. It has been reported that nitro compounds generate a revers- ible one electron process due to the formation of the nitro radical anion ðRNO  2 Þ and an irreversible three electrons process corresponding to the formation of the hydroxyl- amine (RNHOH) in aprotic media [2,3]. Redox properties control most biological responses of nitro compounds, and the formation of the couple RNO 2 =RNO  2 , seems to be an obligatory intermediate for therapeutic selectivity towards anaerobes [4]. Free radicals are in general reactive species that can be of benefit to an organism, e.g., the radicals produced dur- ing phagocytosis, or it can be a liability and produce DNA damage or lipid peroxidation [5,6]. Furthermore, it can be concluded that Fu can potentially behave as a cyto- toxic drug, which produces the RNO  2 and affects the oxy- gen tension present in cells. The relevance of the latter factor lies in the fact that it permits the rapid reoxidation of the radical. The risk of cytotoxity is minimized in aero- bic mammalian cells [6,7]. Studies on the action of nitroa- romatic drugs suggest that the reduction of the nitro group produces a transient species that interacts with DNA resulting in damage characterized by the helix destabiliza- tion and strand breakage [5]. In common with other DNA-cleavaging drugs containing the nitro group, in vivo experiments have provided clear evidence for free radical-mediated DNA strand cleavage by Fu in a process 1388-2481/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.elecom.2006.02.004 * Corresponding author. Tel.: +98 21 88044051; fax: +98 21 88041344. E-mail addresses: lfotouhi@alzahra.ac.ir, lida_fotouhi@yahoo.com (L. Fotouhi). www.elsevier.com/locate/elecom Electrochemistry Communications 8 (2006) 565–570