Cyclic Voltammetric Studies of Nitroimidazoles in Aqueous Solution with Additions of Cysteine

Tuesday, 26 May 2015
Salon C (Hilton Chicago)
G. M. Darzi and D. K. Smith (San Diego State University)
Nitroimidazoles are antibiotics used to treat many infections by killing the bacteria that causes the infection. For example, metronidazole is a drug that belongs to the class of nitroimidazole antibiotics, and it is used to treat bacterial and protozoal infections. Nitroimidazoles need to be activated by a reduction reaction. Although it has been believed that the active form of this drug was the radical anion, there is increasing evidence which suggests that further reduced forms, such as the nitroso and hydroxylamine, are the active forms of this drug. Both species are known to react with cysteine and this may lead to cell death either by deactivation of key proteins or upsetting the redox balance in the cell.

Because of the high reactivity of the nitroso and hydroxylamine imidazoles, it is not generally possible to prepare and isolate them to study their reactivity directly. However they can be studied indirectly using cyclic voltammetry since upon reduction of the nitro group in aqueous solution new peaks due to the oxidation of the hydroxylamine and reduction of the nitroso can be seen.  By varying the scan rate, information on the stability of these species in aqueous solution can be obtained. Further information on the activity of the nitroso and hydroxylamine forms can be obtained by adding equivalents of cysteine to the cell in order to monitor the rate of reaction between cysteine and the nitroso and hydroxylamine forms of different imidazoles. 

This paper will describe the cyclic voltammetry of 1-methyl-5-nitroimidazole and 1-methyl-2-nitroimidazole in aqueous solution in greater detail. Rough estimates of the lifetimes of nitroso and hydroxylamine derivatives in water will be determined using the current vs. time data at different scan rates. If possible, better estimates of the lifetimes and the rates of reaction with cysteine will be obtained by simulation of the voltammograms.