Nitrogen, reactive

Han HS, Qiao Y, Karabiyikoglu M, Giffard RG, Yenari MA. Influence of mild hypothermia on inducible nitric oxide synthase expression and reactive nitrogen production in experimental stroke and inflammation. J Neurosci 2002 22 3921-3928. 

Carotenoid reactions with ROS or RNS (reactive nitrogen species) would generate prooxidative products. ... 

Brennan M-L and et al. (2002) A tale of two controversies. Defining both the role of peroxidases in nitrotyro-sine formation in vivo using eosinophil peroxidase and myeloperoxidase-deficient mice, and the natnre of the peroxidase-generated reactive nitrogen species. J Biol Chem 277 17415-17427. 

Boje, K.M. and Arora, P.K. (1992). Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res. 587, 250-256. 

Very reactive nitrogen mustards and aziridine-containing molecules are usually too toxic for general therapeutic use, but find use in neoplastic disease. Benzodepa (182) is such an agent. Treatment of ethyl carbamate with phosphorous pentachloride leads to cyanate 180 which readily adds benzyl alcohol to produce carbamate 181. Displacement of the active... 

There are no a-amino fluorides because of the reactivity of this functional combination, and for the same reason, there are few P-amino fluorides. However, when attached to the less reactive nitrogen of a... 

Figure 10.1 Ward cascade showing the cooperation between cytoprotective enzymes and antioxidants for scavenging of reactive oxygen and reactive nitrogen species.

Effects of Reactive Nitrogen Species on Prostaglandin H-Catalyzed Processes... 

It has already been mentioned earlier that similar to LOXs, prostaglandin H synthases can be activated or inhibited by reactive nitrogen species. Nitric oxide may exhibit the inhibitory [58,65,86,101 104] or stimulatory effects [105 110] on PGHSs. Inhibitory effects depend on the ability of nitric oxide to reduce the ferric enzyme to the inactive ferrous form, competition... 

Reactive nitrogen species are another factor of free radical damage in rheumatoid arthritis, although their role is less studied than that of oxygen radicals. Stichtenoth and Frolich [242] pointed out that the inhibition of nitric oxide synthesis had beneficial effects in humans. Mazzetti et al. [243] found that IL-1(3 stimulated NO production in RA chondrocytes. We demonstrated that NO synthase of RA neutrophils generated the enhanced amount of peroxynitrite [234]. Nitric oxide and oxygen radicals are also important inducers of death of human osteoarthritic synoviocytes [244]. 

The latest studies show that reactive nitrogen species play even more important role in asthma development. It was found that exhaled nitrogen oxide, an indicator of eosinophilic airway inflammation, is drastically enhanced in asthmatic patients. Correspondingly, it has been shown that lung damage is characterized by the augmentation of nitrotyrosine and iNOS expression in neutrophils, eosinophils, and macrophages in the airways of asthmatic patients [266],... 

The formation of peroxynitrite in cells and tissue is frequently characterized by the formation of nitrotyrosine. The formation of nitrotyrosine is not a very specific assay of peroxynitrite detection because the other nitrogen oxide may also take part in this process, but peroxynitrite is undoubtedly the most efficient nitrating agent. (Mechanism of tyrosine nitration by peroxynitrite and other reactive nitrogen compounds has been considered in Chapters 21 and 22.)... 

Steric effects on the nucleophile, aniline, were clearly evident. Rate constants for bimolecular attack of 2,6-dimethyl- 70a, 2,6-diethyl- 70b, and 3,5-dimethylaniline 70c at 308 K indicate that the ort/zo-substituted anilines react more than an order of magnitude slower at the same temperature (Table 7). Structure 70c must be able approach the reactive nitrogen more closely.42,43 A comparison of the rate constants for reaction of aniline 72c, /V-methyl- 71a and /V-phenylaniline 71b provides further evidence of steric effects although the very small rate constant for the diphenylamine could also be accounted for by reduced nucleophilicity on account of lone pair resonance into the additional phenyl ring. 

Lack of reactivity towards SN2 reactions at nitrogen would in itself account for low mutagenic activity. However, the tert-butyl groups on 31c f and 32a,b are well removed from the reactive nitrogen and, as well, SN2 reactions of mutagens 31c e with A-methylaniline in methanol at 303 °C occur with relatively similar rate constants to that of unsubstituted 28a, and of mono tert-butylated systems 28i and 31 a,b (Table 18). 

Notably, A-(2,6-dimethylbenzyloxy)-A-acetoxybenzamide 37a and N-acetoxy-A-butoxy-3,5-dimethylbenzamide 29u (Fig. 34, black squares, Table 17, entries 39 and 40) were well modelled by QSAR (4). The difference between predicted and observed activities for 37a (—0.03) and A -acetoxy-TV-isopropoxybenzamide 25f (0.04) (Table 17, entry 4) suggests that steric effects proximate to the reactive nitrogen but on the alkoxyl side chain are less important in terms of reactivity with DNA. This is most probably a consequence of the greater flexibility in this side chain relative to the acyloxyl or amide groups. 

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