Nitro compounds, free-radical reduction

Action of aromatic nitro compounds on polymerization Reduction of aromatic nitro compounds Formation of nitroso aimpounds Reduction of aromatic ring Diazotization of amino nitro compounds 1,3-Cycloadditiun of nitro compr unds Thermal stability of aromatic nitro compounds Free radicals Furoxanes References... 

Figure 12. ESR spectra of nitro-anion free radicals from the microsomal reduction of nitro compounds, a. Radicals from the anaerobic incubation of 2 mM nitrobenzene with an NADPH-generating system and 1.5 mg/ml hepatic microsomes b, radicals from the anaerobic incubation of 1 mM nitrofurantoin with an NADPH-generating system and 1 mg/ml hepatic microsomes. From [88,169], with permission.

In fact, with a few exceptions, neither 02 nor nitro compounds react with free radicals by ET (as would be required for an electron affinity relationship in its proper sense) but rather undergo addition reactions. The ensuing radicals show different decay routes as is discussed in Chapter 6.3. When DNA is irradiated in deoxygenated aqueous solution in the presence of 14C-labeled mitronidazole, some of the sensitizer remains attached to DNA (Willson et al. 1974). Misonidazole and practically all other nitroimidazoles have a lower reduction potential than 02, and much higher concentrations have to administered to achieve the same effect (Whillans and Hunt 1982). 

Wardman P, Dennis MF, Everett SA, Patel KB, Stratford MRL, Tracy M (2003) Radicals from one-electron reduction of nitro compounds, aromatic N-oxides and quinones the kinetic basis for hypoxia-selective, bioreductive drugs. Biochem Soc Symp 61 171-194 Warman JM, de Haas MP, Hummel A, van Lith D, VerberneJB, Loman H (1980) A pulse radiolysis conductivity study of frozen aqueous solutions of DNA. Int J Radiat Biol 38 459-459 Warman JM, de Haas MP, Rupprecht A (1996) DNA a molecular wire Chem Phys Lett 249 319-322 Warters RL, Lyons BW (1992) Variation in radiation-induced formation of DNA double-strand breaks as a function of chromatin structure. Radiat Res 130 309-318 Warters RL, Hofer KG, Harris CR, Smith JM (1977) Radionuclide toxicity in cultured mammalian cells Elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 12 389-407 Weiland B, Huttermann J (1998) Free radicals from X-irradiated, dry and hydrated lyophilized DNA as studies by electron spin resonance spectroscopy analysis of spectral components between 77 K and room temperature. Int J Radiat Biol 74 341-358 Weinfeld M, Soderlind K-JM (1991) 32P-Postlabeling detection of radiation-induced DNA-damage identification and estimation of thymine glycols and phosphoglycolate termini. Biochemistry 30 1091-1097... 

Many xenobiotics, including a wide variety of quinones and nitro compounds, will accept an electron from almost any redox flavoenzyme. The microsomal reduction of nitroaromatic compounds, quinones, quinone-imines, some azoaromatic compounds, paraquat, and tetrazolium salts is catalyzed by NADPH-cytochrome P-450 reductase [44], One-electron transfer to these electron acceptors has been proved to be obligatory in the case of quinone and nitro compounds, and is probably obligatory in other cases as well. Therefore, a reduction of an aromatic compound by NADPH-cytochrome P-450 reductase can probably be assumed to form a free radical metabolite. In contrast, free radical formation by reductive dehalogenation is totally cytochrome P-450-dependent, with the reductase being inactive. 

Nitro compounds are also able to be reduced by stannanes under free-radical conditions. For example, Kitayama described the reduction of the nitro moiety in 74 by the action of BubSuH during his preparation of pheromones for Bactrocera Nigrotibialis, Andrem Wilkella and Andrena Haemorrhoa (equation 47). Petrini and coworkers reported the selective reduction of the nitro group in a series of ft), ft)-dichloro-ft)-alkanoates (75) it is interesting to note that the chlorine atoms remain intact during the reaction with Bu3SnH (equation 48). Witczak and coworkers described the reduction of substrate (76)... 

Redox processes involving 178 have also been studied.Anodic oxidation of thianthrene has been eifected in a wide variety of solvents. Use of trifluoracetic acid gives stable solutions of 178 and, if perchloric acid is included, the solid perchlorate salt may be isolated on evaporation of the solvent after electrolysis. Dichloromethane at low temperatures has been used and, at the opposite extreme, fused aluminum chloride-sodium chloride mixtures. " Propylene carbonate permits the ready formation of 178, whereas the inclusion of water in solvent mixtures gives an electrochemical means of sulfoxidizing thianthrene. Reversible oxidation of 178 to thianthrenium dication may be brought about in customary solvents such as nitriles, nitro compounds, and dichloromethane if the solvent is treated with neutral alumina immediately before voltammetry addition of trifluoracetic anhydride to trifluoracetic acid equally ensures a water-free medium. The availability of anhydrous solvent systems which permit the reversible oxidation and reduction of 178 has enabled the determination of the equilibrium constants for the disproportionation of the radical and for its equilibria with other aromatic materials. ... 

P. Wardman, M.F. Dennis, S.A. Everett, K.B. Patel, M.R.L. Stratford and M. Tracy, Radicals from one-electron reduction of nitro compounds, aromatic Af-oxides, and quinones the kinetic basis for hypoxia-selective, bioreductive drags, in Free Radicals and Oxidative Stress Environment, Drags and Food Additives (Biochemical Society Symposium No. 61), C. Rice-Evans, B. Halliwell and G.G. Lunt (eds.), Portland Press, London, 1995, p. 171. 

Substituted benzenediazonium tetrafluoroborates were reduced on Cu, Fe, Ti, Mo, Al, Zn and Ni electrodes in aqueous solution in the presence of acrylamide, in order to use the free radicals formed by the 1-electron mechanism as a polymerization initiator Only when Cu cathodes were used was a high degree of conversion of acrylamide achieved. With Fe cathodes, the polymerization occurred to a lesser extent and with the other metals it did not exceed 5-7%. No explanation was offered for this fact and a catalytic effect of Cu or Cu ions on the reduction of the diazonium salts cannot be excluded. The 4-methoxy and 4-methyl derivatives proved to be the most effective initiators with almost no polymerization being observed with the 4-nitro compound. These results were explained by a competitive reaction of the intermediate free radical with H2O. The occurrence of the polymerization by a radical mechanism was proved by using hydroquinone as an inhibitor, and this fact confirms the le mechanism for the electrochemical reduction of the diazonium salts. 

---