Nitroxyl species

It can be seen that the formation of N20 through the cleavage of the N N bond, as occurring for other hydrazines, is avoided. The nucleophile is able to form a very stable product, azomethane, by transferring two electrons and protons. Thus, the nitroxyl species, [Fen(CN)5 H15NO]3 ", can be formed in Eq. (17) and survive enough to react with... 

Electrophilic attack at coordinated NO may occur at the nitrosyl nitrogen, at the nitrosyl oxygen, or at the metal.96 An example of the first situation is the oxidative addition of acids to electron-rich nitrosyl complexes giving nitroxyl species 112... 

NMR ( H, 13C, 15N) data show that there is a haem-histidine cross-link in cyanobacterial haemoglobins from Synechocyctis sp. PCC 6803 and Synecho-coccus sp. PCC 7002.199 Proton NMR spectroscopy was used to study the interaction of cytochrome c with micelles of sodium dodecyl sulfate.200 The transient HNO ( nitroxyl ) species can be trapped as an adduct with de-oxymyoglobin, i.e. Mb-HNO, with a proton chemical shift of the iron-bound HNO at 14.8 ppm.201 H and 31P NMR spectroscopy was used to probe the role of myoglobin as a scavenger of cellular NO in myocardium.202... 

The nitroxyl species formed in the decomposition of trioxodinitrate (Angeli s Salt),... 

The nitroxyl species, which under the conditions studied largely exists as [NO], undergoes a rapid dimerization forming dinitrogen(i) oxide and water. There is some disagreement as to what happens at lower pH values. Nitrite is undoubtedly involved, and the most likely explanation is set out in reaction (12). A free-radical chain... 

F. 32 Amide activation via bond-weakening PCET to nitroxyl species. Adapted with permission from [233], Copyright 2015 American Chemical Society... 

The formation of N2O takes place by the recombination of two nitroxyl species (step 6). N2O can decompose into N2, involving an oxidation of an oxygen vacancy site as shown in step 7. 

An important point about HAS is that the nitroxyl species is regenerative. However, the cyclic regeneration eventually ends. Some of the regenerative products are inefficient radical scavengers and some of the stabilizer is lost during exposure. The high molecular weight compounds have been shown to be effective as thermal stabilizers. 

The formation of diphenylphosphino radicals on photolysis of triphenyl-phosphine, diphenylphosphine, and tetraphenylbiphosphine has been verified. In the case of the reactions of the phosphines, the radicals were trapped with t-nitrosobutane and the resultant nitroxyl radical [Ph2PN(0)Bu ] was identified by e.s.r. The nitroxyl radical has a small P splitting constant, demonstrating that there is no extensive delocalization onto the phosphorus atom. The e.s.r. spectrum of diphenylphosphino radicals, generated by photolysis of tetraphenylbiphosphine in benzene at 77 K, has been observed. When methanolic solutions of the biphosphine or triphenylphosphine are flash-photolysed, a transient species having Amax = 330 nm and which decays by first-order kinetics (A 4 x 10 s )... 

Organic carbamates (RNHCOO-) commonly display monodentate coordination, as exemplified in the structurally characterized tetrahedral Co(bmc)2Cl2,438 (bmc = lV-(benzimidazoyl-2-yl)-O-methylcarbamate). An unusual route to a carbamato complex involves the reaction of Co2(CO)8 in the presence of a fourfold excess of the stable radical species tmpo, which yields the blue Co40(OOCNC9H18)6 cluster, presumably via a Co(CO)2(tmpo) intermediate, with the nitroxyl radical serving as oxidant.439... 

One other aspect of the photolysis of coordinate spin labeled derivatives is of interest. Nitroxides are good free radical scavengers (123). As a result, when methyl-cobalamin is photolyzed in the presence of a nitroxide, the methyl radical generated will react with the free nitroxide and cause disappearance of the ESR spectrum (123). However, once the nitroxide is coordinated it is no longer susceptible to attack by free radicals. Thus the nitroxyl function is quite well protected from approach by other species. 

A new cyclic mechanism of chain termination by nitroxyl radicals, including the formation of aminyl radicals as intermediate species, has been proposed by Korcek and coworkers [42,43]. It was shown that the addition of 4,4 -dioctyldiphenylnitroxyl radical to the hexa-decane that is oxidized (T = 433 K) leads to the formation of the corresponding diphenyl-amine as an intermediate compound during its transformations. The following cyclic mechanism of chain termination was suggested ... 

In contrast to nitric oxide, which is firmly identified in biological systems and for which numerous (but not all) functions are known, the participation of other nitrogen species in biological processes is still hypothetical. At present, the most interest is drawn to the very reactive nitroxyl anion NOT It has been shown that nitroxyl (or its conjugate acid, HNO)... 

It should be noted that a major difficulty in the detection of nitroxyl anion is explained by the impossibility to apply ESR spectroscopy because nitroxyl is not a free radical. Moreover, the use of spin traps such as iron iV-methyl-D-glucamine dithiocarbamate (Fe-MGD) to distinguish NO and NO production by NO synthase failed because both nitrogen species reacted with this spin trap [87]. 

Second, nitroxyl radicals, which are generated either by a one-electron oxidation of SENAs (Eq. 1, Scheme 3.98) or by the addition of radical species to silyl nitronates (Eq. 2, Scheme 3.98), are rather stable and, consequently, can act as kinetically independent species. 

C-Nitroso compounds, oximes, N-hydroxyguanidines and N-hydroxyureas each contain an N-O bond and release nitric oxide (NO) or one of its redox forms under some conditions. The nitrogen atom of a C-nitroso compound formally exists in the +1 oxidation state, the same oxidation state as nitroxyl (HNO), the one-electron reduced form of N O. The nitrogen atoms of oximes, N-hydroxyguanidines, and N-hydroxyureas each formally exist in the -1 oxidation state, the same oxidation state as hydroxylamine. Consequently, the direct formation of NO (formal oxidation state = +2) from any of these species requires oxidation, one electron for a C-nitroso compound and three electrons for an oxime, N-hydroxyguanidine or N-hydroxyurea. This chapter summarizes the syntheses and properties, NO-releasing mechanisms and the known structure-activity relationships of these compounds. 

N, O-Diacylated or O-alkylated N-hydroxysulfonamides release nitroxyl (HNO) upon hydrolysis or metabolic dealkylation, as determined by gas chromatographic identification of nitrous oxide in the reaction headspace [27-29, 38]. Scheme 7.5 depicts the decomposition of a representative compound (7) to a C-acyl nitroso species that hydrolyzes to yield HNO. Either hydrolysis or metabolism removes the O-acyl or O-alkyl group to give an N-hydroxy species that rapidly decomposes to give a sulfinic acid and an acyl nitroso species. This C-acyl nitroso species (8) hydrolyzes to the carboxylic acid and HNO (Scheme 7.5). These compounds demonstrate the ability to relax smooth muscle preparations in vitro and also inhibit aldehyde dehydrogenase, similar to other HNO donors [27, 29]. 

Nitric oxide formation from hydroxyurea requires a three-electron oxidation (Scheme 7.15) [114]. Treatment of hydroxyurea with a variety of chemical oxidants produces NO or NO-related species , including nitroxyl (HNO), and these reactions have recently been extensively reviewed [114]. Many of these reactions proceed either through the nitroxide radical (25) or a C-nitroso intermediate (26, Scheme 7.15) [114]. The remainder of the hydroxyurea molecule may decompose into formamide or carbon dioxide and ammonia, depending on the conditions and type of oxidant (one-electron vs. two electron) employed. 

Later even more complexity was demonstrated (Makino et al., 1992) in the reaction between DMPO and Fe111 in water. The HO-DMPO" formed was transformed into a hydroxamic acid [24] which is a tautomer of 2-hydroxy-DMPO [25] in a Fenton system transfer of a hydroxyl (cf. p. 133) from the ligand-FeOOH complex to either of these species leads to additional epr-active nitroxyls [26] and [27] in reaction (72). 

The radical addition products are nitroxyl radicals which are readily characterized by means of their EPR spectra. We used both radical trapping agents to carry out some of the studies. The PBN system is less diagnostic because it is not as sensitive to trapping all the radical species as DMPO. The data in Table II are for the DMPO trap. We also generated hydroxyl... 

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