Nitroxyl ion

Breakup as indicated by the arrows on this structure would give Fe(III)-OH, citrulline, and 0=N-H, nitroxyl. This is one electron (e + H+) more reduced than NO. Perhaps the adduct forms from Fe(ffl)-0-0. On the other hand, there is evidence that NO synthases may produce nitroxyl or nitroxyl ion NO- as the initial product.537-538 NO and other products such as NzO and N02 may arise rapidly in subsequent reactions. Nitrite is a major oxidation product of NO in tissues.5383 The chemistry of NO in biological systems is complex and not yet fully understood. See also pp. 1754,1755. 

Nitronium ion is sometimes called nitryl or (more correctly) nitroxyl ion (see p. 13). 

Chapters 11,18). It binds to the iron of heme groups in either the Fe or Fe " form and also reacts with thiol groups of proteins and small molecules to form S-nitrosothiols (R-S-N=0). It reacts with the heme iron of myoglobin and hemoglobin and, by transfer of one electron, can oxidize the iron of hemoglobin to the Fe + methemoglobin with formation of the nitroxyl ion NO This reaction may be a... 

Biochemical routes for the formation of nitroxyl ions are shown in Fig. 5.25 but without considering inorganic or non-enzymatic solution chemistry. In cells, reac-... 

Hughes, M. N. (1999) Relationships between nitric oxide, nitroxyl ion, nitrosonium cation and peroxynitrite, Biochimica et Biophysica Acta (BBA) - Bioenergetics 1411, 263-272 Humboldt, A. v. (1799) Versuche fiber die chemische Zerlegung des Luftkreises und fiber einige andere Gegenstande der Naturlehre. Vieweg, Braunschweig, 258 pp. 

Nitroxyl radicals of diarylamines can also be obtained on oxidation with hydrogen peroxide in the presence of vanadium ions. Resonance helps stabili2e these radicals. Eor example, the nitroxide from 4,4 -dimethoxydiphenylainine [63619-50-1] is stable for years, whereas the radical from the unsubstituted diphenylamine caimot be isolated. Substitution in the ortho and para positions also increases the stabiUties of these nitroxides by inhibiting coupling reactions at these sites. However, they are not as stable as the stericaHy hindered tetramethylpiperidyl radical. 

The subj ect has been treated as part of a general discussion of N O-donors in a number of reviews [1-4]. This chapter will briefly introduce the general properties of these systems and the chief methods to synthesise them, after which it will concentrate on their NO-donor properties and NO-dependent biological activities. The term NO will be used here as a family name, embracing not only nitric oxide (NO ) but also its two redox forms, nitroxyl (HNO) and nitrosonium ion (NO+), which play important roles in the complex signalling system connected with NO [5]. The specific redox form involved in the NO-release will be indicated, if known, when necessary for the discussion. 

Molsidomine (8.159, Fig. 8.18), a very special example of a carbamate prodrug that acts by vascular smooth muscle relaxation, is an anti-angina agent effective mainly in the treatment of myocardial ischemia [207], Molsidomine undergoes enzymatic hydrolysis in the liver to form the imine 8.160 (Fig. 8.18) [208]. This metabolite is inactive and unstable, breaking down spontaneously to the A-nitroso secondary metabolite known as Sinl A (8.161, Fig. 8.18). The latter was found to be active, but there are reasons to believe that it acts by releasing nitrogen monoxide in the form of nitroxyl (HNO), which dissociates to the nitroxide ion NO, i. e., the reduced form of NO. 

Electrochemical bromination of long chain alkenes in a two-phase water-organic medium presents a difficulty because the bromine, which is generated, is held in the aqueous phase as the tribromide ion. A catalytic amount of the nitroxyl 35 acts... 

The first clues that compounds of structure I might be involved in nitrosamine-forming reactions came during the study of tertiary amine nitrosations. Smith and Loeppky had proposed ( ) in their detailed, classical investigation of the mechanism of this reaction that the first steps involve nitrosammonium ion formation followed by elimination of nitroxyl (HNO). The resulting immonium ion was postulated to hydrolyze to the secondary amine, which reacted with nitrosating agent to form the observed product. These mechanistic proposals are summarized in Fig. 2a. 

A similar mechanism was invoked by Ohshima and Kawabata (2) to account for their results in the nitrosation of tertiary amines and amine oxides. In applying these concepts to the nitrosative dealkylation of tetraalkyltetrazenes, Michejda al. 5) introduced an interesting variant by suggesting that immonium ions could be formed in two successive one-electron oxidation steps (for example by ferric ion oxidation of tertiary amine to the radical cation followed by radical abstraction of a hydrogen atom from the alpha position), rather than exclusively through the one-step removal of a hydride ion as nitroxyl. The resulting immonium ion was again considered to react directly with nitrite to produce the N-nitroso derivative. These reactions are summarized in Fig. 2b. 

Nitrosamine formation is not the only conceivable fragmentation mechanism for compounds of structure I. By analogy to the nitrosative dealkylation reactions discussed above, one might predict that such compounds could also undergo cis elimination of nitroxyl in amide-forming reactions. Such a transformation has possibly been observed (14). During an attempt to synthesize the nitrosamino aldehyde VIII from immonium ion IX, Hecht coworkers were able to isolate only 5-10% of the desired product. The major product proved to be N-methyl-2-pyrrolidone, as shown in Fig. 10. We interpret this as evidence that an intermediate such as li can fragment not only by the Fig. 1... 

Nitric oxide may be oxidized by one electron to give nitrosonium ion (NO ) or reduced by one electron to form nitroxyl anion (NO"), which are important intermediates in the chemistry of nitric oxide (Stamler et al., 1992a). 

Although much of the biological literature focuses on nitrosating reactions of nitric oxide, chemically nitric oxide is a moderate one-electron oxidant, making formation of nitroxyl anion feasible under physiological conditions. The reduction potential to reduce nitric oxide to nitroxyl anion is +0.39 V, whereas it requires +1.2 V to oxidize nitric oxide to nitrosonium ion. Nitrosating reactions of nitric oxide are often mediated by conversion of nitric oxide to another nitrogen oxide species or by direct reaction with transition metals (Wade and Castro, 1990). 

The direct reaction of superoxide with nitric oxide is only one of at least four possible pathways that can form peroxynitrite (Fig. 40). For example, superoxide should also efficiently reduce nitrosyldioxyl radical to peroxynitrite. Alternatively, nitric oxide may be reduced to nitroxyl anion, which reacts with oxygen to form peroxynitrite. Superoxide dismutase could even catalyze the formation of peroxynitrite, since reduced (Cu or cuprous) superoxide dismutase can reduce nitric oxide to nitroxyl anion (Murphy and Sies, 1991). Thus, superoxide might first reduce superoxide dismutase to the cuprous form, with nitric oxide reacting with reduced superoxide dismutase to produce nitroxyl anion. A fourth pathway to form peroxynitrite is by the rapid reaction of nitrosonium ion (NO" ) with hydrogen peroxide. This is a convenient synthetic route for experimental studies (Reed et al., 1974), but not likely to be physiologically relevant due to the low concentrations of hydrogen peroxide and the difficulty of oxidizing nitric oxide to nitrosonium ion. 

Four routes to form peroxynitrite from nitric oxide. The reaction of nitric oxide with superoxide is only one mechanism leading to the formation of peroxynitrite. Supetoxide could also reduce the nitrosyidioxyl radical. If nitric oxide is directly reduced to nitroxyl anion, it will react with molecular oxygen to form peroxynitrite. At acidic pH, nitrite may form nitrous acid and nitrosonium ion, which reacts with hydrogen peroxide to form peroxynitrite. 

The positiveNO ion occurs in compounds like nitroxyl perchlorate, N0 C10, but there is a negative NO ion in nitrites. This negative ion, NO , can be given a structure with only octets, as well, e.g. 

This behavior is not consistent with the formation of Wurster ions, which have been postulated as intermediates and in fact demonstrated to occur in polar solvents (3) but indicates the formation of a nitroxyl radical intermediate in the presence of oxygen and its decay when the oxygen is removed. [Sullivan (23) gives a number of references to nitroxyl radicals.] The possibility that R2N radicals are formed as a... 

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