PA-824 (2-nitro-6-(4-trifluoromethoxy-benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine) is being tested as antituberculosis drug. Little is known on the action mechanism of PA-824; however the reduction of the nitro group seems to be a key step in the metabolic activation, as is observed for the well-known bactericidal metronidazole. Consequently, this paper is focused on the cyclic voltammetric behavior of PA-824 with the aim of revealing the formation and stability of the corresponding nitro radical anion and its comparison with the metronidazole behavior.Both compounds PA-824 and metronidazole reveal, in aprotic medium (DMSO+0.1 tetrabutylammonium hexafluorophosphate), a similar reduction pattern showing a well-resolved couple due to nitro reduction to form the corresponding nitro radical anion. The electrode reaction obeys an EC2 mechanism with a dimerization reaction as the chemical step in aprotic medium. Using cyclic voltammetry theory for a dimerization reaction we have calculated the second-order decay constants, k(2,dim) and the half-life time, t(1)/(2), for the nitro radical anions formed from PA-824 and metronidazole. We have obtained k(2,dim) values of 2.22 x 10(2) and 2.58 x 10(4) M(-1)s(-1) for metronidazole and PA-824, respectively. Our voltammetric results show that the PA-824 nitro radical anion requires more energy for formation (about 200 mV) and it is approximately 100 times less stable than the metronidazole radical anion. (C) 2003 Elsevier B.V. All rights reserved.