Nitrite organics

Nitrites Organic nitrites in contact with ammonium salts, cyanides... 

Hyponitrites can be prepared in variable (low) yields by several routes of which the commonest are reduction of aqueous nitrite solutions using sodium (or magnesium) amalgam, and condensation of organic nitrites with hydroxylamine in NaOEt/EtOH ... 

Nitrito- Compounds. Organic compds containing one or several —O.N 0 groups which are called oxynitroso radicals. These compds are also known as organic nitrites. Some are expl, as, for example, Methyl Nitrite, CHj.O.NO (see in this Vol). They are not as stable as the corresponding nitrates and nitrocompds Ref Hackh s (1972), 457... 

Kielbasa W, Fung HL Pharmacokinetics of a model organic nitrite inhalant and its alcohol metabolite in rats. Drug Metab Dispos 28 386-391, 2000... 

Photochemical elimination reactions include all those photoinduced reactions resulting in the loss of one or more fragments from the excited molecule. Loss of carbon monoxide from type I or a-cleavage of carbonyl compounds has been previously considered in Chapter 3. Other types of photoeliminations, to be discussed here, include loss of molecular nitrogen from azo, diazo, and azido compounds, loss of nitric oxide from organic nitrites, and loss of sulfur dioxide and other miscellaneous species. 

Organic nitrites display a weak long-wavelength absorption (n -> n ) involving excitation of a nonbonding electron on nitrogen. Photolysis has been found to result in photodissociation of the RO—NO bond to produce alkoxy radicals and nitric oxide ... 

The photochemical cleavage of organic nitrites 224), also known as Barton reaction, has been widely utilized in the steroid field. The mechanistic sequence as described in (2.14) consists of ... 

Nitrites Nitrobenzene Nitroethane Nitrogen trichloride Organic nitrites in contact with ammonium salts, cyanides Nitric acid, nitrous oxide, silver perchlorate Hydroxides, hydrocarbons, metal oxides Ammonia, As, hydrogen sulfide, nitrogen dioxide, organic matter, ozone, phosphine, phosphorus, KCN, KOH, Se, dibutyl ether... 

Fung and colleagues examined the metabolic conversion of organic nitrates in sub-cellular fractions of bovine coronary artery smooth muscle cells [66, 67]. They found NO-generating capacity to be present in membrane fractions and, with the use of marker enzymes, identified plasma membrane as the primary location. The enzyme involved in bioconversion was not glutathione-S-transferase [68] and differed from those that catalyse activation of organic nitrites [69]. Partial purification [70] established that the molecular sizes of the native enzyme and subunits were approximately 200 kDa and 58 kDa respectively, and that enzymic activity depends on the presence of a free thiol group. 

Fig. 2.4 Schematic diagram showing XOR-catalysed reduction of nitrates and nitrites. Organic nitrates are reduced at the FAD site to inorganic nitrite this can be further reduced to NO at the molybdenum (Mo) site. Organic nitrites are reduced at the FAD site, in this case, directly to NO. Inorganic nitrates are reduced at Mo. Adapted from Harrison [73].

As mentioned earlier, the therapeutic use of organic nitrites [4] actually predates that of organic nitrates [1], Clinical utilisation of nitrites has, however, been very much less and this is reflected in the relatively sparse attention given to their mechanisms of action. Alkyl nitrites react readily with thiols to form S-nitrosothiols [122], which show biological effects similar to those of NO [11]. Nevertheless, glutathione-S-transferase has been implicated in the metabolism of organic nitrites, via intermediate... 

Kowaluk, E. A., Fung, H-L., Vascular nitric oxide-generating activities for organic nitrites and organic nitrates are distinct. J. Phamacol. Exp. Ther 259 (1991), p. 519-525... 

T. A., Eisenthal, R., Harrison, R., Reduction of organic nitrites to nitric oxide catalysed by xanthine oxidase possible role in metabolism of nitrovasodilators. Biochem. Biophys. Res. Commun. 270 (2000), p. 880-885... 

Meyer, D. J., Kramer, H., Ketterer B., Human glutathione transferase catalysis of the formation of S-nitrosoglutathione from organic nitrites plus glutathione. FEBS Lett. 351 (1994), p. 427-428... 

Ji,Y., Akerboom,T.P.M., Sies, H., Microsomal formation of S-nitrosoglutathione from organic nitrites possible role of membrane-bound glutathione transferase. Biochem. J. 313 (1996), p. 377-380... 

Enzymatic conversion of nitrite to RSNOs has been reported. Glutathione-S-transferase catalyzed generation of RSNOs from organic nitrites was initially demonstrated in rat liver microsomes (Ji et ah, 1996). Subsequently, this activity has been identified in the rat heart and lung GSTs (Akerboom et al., 1997). 

A rather different route, involving formation of an organic nitrite by a process requiring reduced flavin, has been proposed [67]. The organic nitrite then nitrosates a cellular thiol and NO is formed from the nitrosothiol (Eqs. (14) and (15)). 

They are more potent than nitrates and there is no development of tolerance [78]. Their drawbacks are that they are very volatile (and therefore difficult to deliver quantitatively) and photochemically and thermally unstable. Organic nitrites are excellent nitrosating agents, particularly for thiols (Eq. (17)). 

Nitrite can be reduced in vivo to NO by oxyhemeoglobin [9], At the same time organic nitrites are substrates for xanthine oxidoreductase and direct reduction to NO occurs under anaerobic conditions [8],... 

For some clinical purposes the volatility of organic nitrites is an advantage as it allows inhalation, but for physiological experimentation the volatility is a serious... 

Diazotization is the reaction of a primary aromatic amine with a nitrosating agent, such as sodium nitrite or, to a lesser extent, with nitrosylsulfuric acid N0S04H, nitrous gases, or organic nitrites in an aqueous acidic solution at a temperature between 0 and 5°C, converting the amine to its diazonium salt ... 

Starting materials which are only sparingly soluble in water may require solvents that are either partially or entirely organic. Diazotization can either be carried out as usual with an aqueous sodium nitrite solution, or alternatively with nitrosylsul-furic acid or an organic nitrite. Appropriate solvents must be stable to the reactants. Examples include aromatic hydrocarbons, chlorohydrocarbons, glycol ethers, nitriles, esters, and dipolar aprotic solvents, such as dimethyl formamide, dimethyl sulfone, tetramethylene sulfone, tetramethyl urea, and N-methylpyrroli-done. 

These compounds contain the fragment R as an alkyl or aryl moiety. In other words, they result from the esterification of an alcohol or a phenol with nitrous acid, nitric acid, phosphoric acid, sulfuric acid, or sulfamic acid, respectively. Many of the esters to be examined in this chapter must be activated prior to eliciting their effects, e.g., the organic nitrites and nitrates, which act as donors of nitric oxide or an analogous molecule, and phosphates, which are activated by hydrolysis or even by phosphorylation (antiviral agents). Sulfates are very seldom active or used as prodrugs, but they have significance as metabolites and as industrial xenobiotics. 

The reactivity of organic nitrites toward hydrolysis differs markedly from that of organic nitrates. The reaction mechanisms are summarized in Fig. 9.2. The base-catalyzed hydrolysis of organic nitrites (Fig. 9.2,a) is quite slow, in... 

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