Nitroxyl radicals reduction-oxidation

Cyclic chain termination by antioxidants. Oxidation of some substances, such as alcohols or aliphatic amines, gives rise to peroxyl radicals of multiple (oxidative and reductive) activity (see Chapters 7 and 9). In the systems containing such substances, antioxidants are regenerated in the reactions of chain termination. In other words, chain termination occurs as a catalytic cyclic process. The number of chain termination events depends on the proportion between the rates of inhibitor consumption and regeneration reactions. Multiple chain termination may take place, for instance, in polymers. Inhibitors of multiple chain termination are aromatic amines, nitroxyl radicals, and variable-valence metal compounds. 

The general trend of nitrones toward radical reactions can be explained by a variety of reasons (a) their readiness to be transformed into stable nitroxyl radicals as a result of the so-called spin trapping (b) one-electron oxidation into radical cations and (c) one-electron reduction into radical anions (Scheme 2.77, routes C,D and E). Depending on the reaction conditions either route has been... 

When reacted with acetylene in the KOH/DMSO system at 50-60°C, l-hydroxy-2,2,6,6-tetramethyl-4-piperidone oxime (39, X = OH) forms azaindole 40 with a nitroxyl group (R = H X = 6, yield 48%), implying an oxidation-reduction process takes place under the reaction conditions. At elevated temperature (105°C) and with excess acetylene, oxime 39 (X = OH) is converted to 1-vinylazaindole 40 with X = H. Therefore, under more harsh conditions, the KOH/DMSO system acts as a reductant with respect to the nitroxyl radical. 

Nitrate is frequently measured using the Griess reagent as an index of NO produced. NO itself participates in both reduction and oxidation reactions. Single electron reduction of NO yields the nitroxyl anion, whereas oxidation reactions yield the nitrosonium cation and N2O3+, via autoxidation. Both the NO radical and nitrosonium cation can be involved in direct reactions with biological systems, specifically with amino acid residues such as cysteine, with the resultant production of nitrosothiols (see later). 

The most characteristic reaction of hindered nitroxyls is their reduction which results either in the corresponding hydroxylamine or amine. Hydroxylamines, as a rule, are readily oxidized to the corresponding radicals. Oxidation can be accomplished with atmospheric oxygen in the presence of catalytic amounts of heavy metal salts e.g., cupric salts. Pb02 and Kj[Fe(CN)g] can also be used as oxidizing agents. This easily occuring transformation-radical — hydroxylamine —> radical-is the basis for several important syntheses, in particular, electrochemical syntheses of the nitroxyl radicals (4) and (6) (39,40) ... 

The mechanism of ssb enhancement and radiosensitisation may be related in some way to those oxidants which form adducts with the DNA radicals. With the nitroaromatics a plausible enhancement of ssb is the possible H-atom abstraction by the base nitroxyl radical. The reactivity of the nitroxyl adducts with thiols or other reductants has not been studied in detail as there are at least two possible interactions where competition between the nitro-aromatic and a thiol may occur as shown in reactions (11-15). 

The oxidation of some classes of substances (alcohols, aliphatic amines) gives peroxyl radicals, which possess both oxidative and reductive actions. In these systems, a several inhibitors terminate chains and are regenerated again in acts of chain termination catalytic chain termination takes place. The number of chain terminations depends on the ratio of the rates of inhibitor regeneration to its irreversible consumption. In several cases, multiple chain termination is observed in polymers. Inhibitors of multiple chain termination are aromatic amines, nitroxyl radicals, and compounds of variable-valence metals. 

Oxidation of alkenes, sulfides, sulfoxides and amines by alkyl hydroperoxides (ROOH) is catalyzed by [VO(acac)2] (equations 39-42),552 and mechanisms involving association of ROOH with [VO(acac)2] forming Vv compounds have been suggested.552 The reactions of phenoxyl, iminoxyl, nitroxyl, peroxyl and alkoxyl radicals with [VO(acac)2] in solution were studied by kinetic ESR spectroscopy552 and the net reaction was found to be catalytic reduction of the radical, probably also involving initial formation of a Vv compound. 

Inhibition by radical traps, such as TEMPO 17, was used to explain the involvement of radicals in the course of transition metal-catalyzed reactions (Fig. 7). Typical cross-coupling reactions, such as Heck or Suzuki-Miyaura reactions, proceeded even with nitroxyls as substrates, although the yields were sometimes low. Thus, nitroxyls do not necessarily interfere very much with the course of two-electron catalytic processes [79-81]. However, it must be critically mentioned that 17 and related nitroxides are both oxidants and reductants for metal species. 

The above complexes were characterized in various tumor models it was shown that the DNA binding rate for these new complexes is comparable with that of cisplatinum but then-oxidizing effect is opposite the initial cisplatinum accelerates oxidation in model radical reaction the platinum-nitroxyl complexes, on the contrary, inhibit oxidation. From this point of view, it is easy to explain the reduction of the toxicity of the synthesized complexes. 

Radical-radical combination with formation of a diamagnetic product(s) seems unlikely since it is expected that the rate constants for such a process would be independent of the E values. Alternatively, oxidation of the nitroxyls to the corresponding oxoammonium ions could occur and the rates of reaction would be expected to be influenced by the second one-electron reduction potentials (E ) of the substrates however, no... 

It was well known that the nitroxyl free radicals could participate in one-electron reduction reaction in an acidic medium to yield relatively stable diamagnetic products, hydroxypiperidines structure (NOH) and oxopiperidinium cations G O ). Figure 4 shows such one-electron reduction and oxidation reaction of free nitric oxide derivatives. 

Figure 4. The reversible one-electron reduction and oxidation reactions of nitroxyl free radicals.

---