Some Reactions and Properties of Nitro Radical-Anions Important in Biology and Medicine

Abstract

Nitroaromatic compounds, ArNO2 have widespread actual or potential use in medicine and cancer therapy. There is direct proof that free-radical metabolites are involved in many applications, and an appreciation of the conceptual basis for their therapeutic differential; however, an understanding of the detailed mechanisms involved is lacking. Redox properties control most biological responses of nitro compounds, and the characteristics of the one-electron couple: ArNO2/ArNO2 are detailed. The "futile metabolism" of nitroaryl compounds characteristic of most aerobic nitroreductase systems reflects competitioq between natural radical-decay pathways and a one-electron transfer reaction to yield superoxide ion, 02-Prototropic properties control the rate of radical decay, and redox properties control the rate Qf electron transfer to 02 or other acceptors. There are clear parallels in the chemistry of ArNO2 and°2-While nitro radicals have frequently been invoked as damaging species, they are very unreactive (except as simple reductants). It seems likely that reductive metabolism of nitroaryl compounds, although generally involving nitro radical-anions as obligate intermediates (and this is required for therapeutic selectivity towards anaerobes), results in biological damage via reductive metabolites of higher reduction order than the one-electron product.

Cyclic voltammetric determination of free radical species from nitroimidazopyran: a new antituberculosis agent

“…According to the theory of Olmstead et al [17] we have obtained k 2;dim values of 2.22 AE 0.38 Â 10 2 and 1.52 AE 0.24 Â 10 2 M À1 s À1 for metronidazole in DMSO at mercury and a GCE, respectively. Wardman [26] and Henry et al [27], using pulse radiolysis measurements, have previously reported k 2 values of 4.2 Â 10 4 (pH 7.4) and 7.9 Â 10 4 M À1 s À1 (pH 7) for metronidazole in aqueous media. Tocher and Edwards [28], using electrochemical measurements, have reported a k 2 value of 8.4 Â 10 4 M À1 s À1 which was obtained as an extrapolation in 100 % aqueous media.…”

Reactions of the nitro radical anion of metronidazole in aqueous and mixed solvent: a cyclic voltammetric study

“…Earlier studies using pulse radiolysis [42,71,72] shows that, in aqueous solution, the nitro radical anions of nitroimidazoles undergo a bimolecular disproportionation reaction. In studies using cyclic voltammetry in mixed aqueous solvents where the nitro radical anion is highly stabilised and both the cathodic and anodic waves are observed, the lifetime of the nitro radical anion, the one-electron reduced species of metronidazole as well as the rate constant for its disproportionation reaction could be determined using the return to forward peak current ratio, I pa =I pc at different scan rates [68].…”

“…The reactivity of nitro radical anions from most of the nitrocompounds has been studied mainly by the pulse radiolysis [39][40][41][42] technique. Recently electrochemical techniques like cyclic voltammetry [43][44][45][46][47][48][49][50][51][52][53][54][55][56] have been used to study the behaviour of the nitro radical anions.…”

Electrochemical reduction of 2-nitroimidazole in aprotic medium: Influence of its dissociation equilibrium on the reduction mechanism

“…Their use as radiosensitizers takes advantage of their cytotoxicity in hypoxic mammalian cells, increasing sensitivity to the radiation of cancerigenic tumors [1][2][3][4]. Their antimicrobial characteristic takes advantage of their selective toxicity towards anaerobic microorganisms, permitting their extensive use in the treatment of infectious diseases [5][6][7][8][9][10][11]. There are numerous studies aiming at the electrochemical aspects of nitroimidazolic compounds.…”