S-Nitrosothiols

Some acyclic sulfur-nitrogen compounds also exhibit intense colours. For example, S-nitrosothiols RSNO are either green, red or pink (Section 9.7). Their UV-visible spectra show an intense band in the 330-350 nm region (no it ) and a weaker band in the visible region at 550-600 nm... 

The most convenient route to S-nitrosothiol formation is the nitrosation of thiols by nitrous acid (Eq. 9.13). 

In solution the cis and trans isomers may co-exist, as demonstrated by N NMR and UV-visible spectra. The N NMR chemical shift of the trans isomer is shifted ca. 60 ppm downfield relative to the cis isomer." The visible absorption band of S-nitrosothiols corresponds to a weak n K transition in the 520-590 nm region. The absorption maxima of trans conformers are red-shifted by ca. 30 nm relative to those of the cis isomer. Two absorptions are observed in the 520-590 nm region in the experimental spectra of RSNO derivatives." ... 

X.J. Zhang, Y. Kislyak, J. Lin, A. Dickson, L. Cardosa, M. Broderick, and H. Fein, Nanometer size electrode for nitric oxide and S-nitrosothiols measurement. Electrochem. Commun. 4, 11-16 (2002). 

S-nitrosothiols (RSNO) have emerged as important species in the storage and transport of nitric oxide. As NO donors these S-N compounds have potential medical applications in the treatment of blood circulation problems. 

S -nitrosothiols, several of which occur naturally, e.g., iS -nitrosocysteine and S-nitrosoglutathione, have an important role in NO transport and regulation in biological systems. Potential applications of RSNO compounds include their use as vasodilators in the treatment of angina and in the search for a cure for male impotence.11 The most convenient route to S-nitrosothiol formation is the nitrosation of thiols. 

S -nitrosothiols may adopt either cis (64a) or trans (64b) conformations with respect to the S-N bond. S-nitrosocaptopril189 assumes a cis arrangement, while the trans isomer pertains in the solid state for S-nitroso-TV-acetylpenic-illamine and Ph3CSN0.190 The S-N bond lengths are typical for a single bond. Nevertheless, there is a significant barrier to rotation about the S-N bond.189 192 In solution the cis and trans isomers may co-exist. 

Stable S-nitrosothiols and S-nitrososelenols have also been generated by attaching bowl-shaped aryl substituents to the nitrogen centre.193,194 The alkyl derivative (Me3Si)3CSeNO is prepared by nitrosation of (Me3Si)3CSeH with tert-butylnitrite.195... 

The ability of S -nitrosothiols to mimic many of the biological properties of NO itself may emanate from in vivo decomposition to generate NO. This decomposition is catalysed by Cu2+,n and may be important in the development of thrombo-resistant devices used in kidney dialysis or coronary by-pass surgery.196 It is also possible that direct transfer of NO from RSNO occurs in biological systems.197... 

Recently, it has been found that NO donors inhibit HIV-1 replication in acutely infected human peripheral blood mononuclear cells (PBMCs), and have an additive inhibitory effect on HIV-1 replication in combination with 3 -azido-3 -deoxythymisylate (AZT) [139, 140]. S-nitrosothiols (RSNOs) inhibit HIV-1 replication at a step in the viral replicative cycle after reverse transcription, but before or during viral protein expression through a cGMP-independent mechanism. In the latently infected U1 cell line, NO donors and intracellular NO production stimulate HIV-1 reactivation. These studies suggest that NO both inhibits HIV-1 replication in acutely infected cells and stimulates HIV-1 reactivation in chronically infected cells. Thus, NO donors may be useful in the treatment of HIV-1 disease by inhibiting acute infection, or reactivating a latent virus. 

It is worth noting that S-nitrosothiols, originally implicated by Ignarro and colleagues in the bioactivation of organic nitrates (Scheme 2.1), have been shown to be reduced to NO in the presence of XOR [94]. 

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... 

Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside, and nitric oxide evidence for the involvement of S-nitrosothiols as active intermediates. /. Pharmacol. Exp. Then 218 (1981), p. 739-749... 

Ignarro, L. J., Gruetter, C. A., Requirement of thiols for activation of coronary arterial guanylate cyclase by glycerol trinitrate and sodium nitrite Possible involvement of S-nitrosothiols. Biochim. Biophys. 

Kowaluk, E. A., Fung, H-L., Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J. Pharmacol. Exp. Ther. 255 (1990),... 

R., Xanthine oxidase-mediated decomposition of S-nitrosothiols. J. Biol. Chem. 273 (1998), p. 7828-7834... 

Type II nitrosamines have two reaction pathways. One pathway involves nucleophilic attack at the carbon of C=0 to generate a tetrahedral intermediate which decomposes to an active diazotate ion (R-N=N-0 ). The other pathway involves the nucleophililc attack on the nitrogen of the nitroso group resulting in denitrosation (Scheme 3.5). The nucleophile can be a biologically prevalent thiol, therefore type II compounds are often used as NO donors for the formation of S-nitrosothiols [67, 68]. 

Fig. 4.1 Schematic illustration with selected bond lengths, of the lowest energy conformations of the S-nitrosothiols trans-HSNO...

Alpert, C., Ramdev, N., George, D., Loscalzo, J., Detection of S-nitrosothiols and other nitric oxide derivatives by... 

Baciu, C., Gauld, J. W., An assessment of theoretical methods for the calculation of accurate stmctures and S-N bond dissociation energies of S-nitrosothiols (RSNOs),/. Phys. 

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