Discovery of Nitric Oxide

The discovery of nitric oxide in living organisms was a great event in the development of free radical studies in biology. NO is a gaseous neutral free radical with relatively long lifetime and at the same time is an active species capable of participating in many chemical reactions. 

Moncada S, Higgs EA The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 2006 147 S193. 

The first volume starts with an introductory chapter by myself on Historical Introduction to Nitrosyl Complexes recounts the discovery of nitric oxide and its complexes and serves as a general broad introduction to the two volumes. This is followed by a pair of chapters by Dr. Hanna Lewandowska on the Coordination Chemistry of Nitrosyls and Its Biological Implications and the Spectroscopic Characterization of Nitrosyl Complexes. A comprehensive overview is presented of the biologically relevant coordination chemistry of nitrosyls and its biochemical consequences in the first chapter. Representative classes of metal nitrosyls are introduced along with the structural and bonding aspects that may have consequences... 

Recent discovery of nitric oxide ( NO), which controls and influences a number of critical physiological processes, as a mammalian metabolic intermediate has stimulated rapid progress of studies on nitric oxide synthase (NOS) [267-269]. The formation of NO from L-arginine in mammalian cells is catalyzed by NOS. The inducible NOS has now been known to contain a cytochrome P-450 type iron-protoporphyrin IX prosthetic group and 1 equiv each of FAD and FMN per subunit [270, 271]. Further, NOS requires NADPH to proceed the reactions. Interestingly, P-450 itself has been demonstrated to catalyze NO synthesis [272, 273]. While the detail of the reaction mechanism is still obscure. Scheme 17 summarizes proposed reaction sequences [269]. 

Since the discovery that nitric oxide is crucially involved in a range of physiological processes and indeed that it is synthesized in vivo from L-arginine (for review articles see References 19-22), there has been intense interest in a range of compounds which might act as NO donors. Consequently, the most studied reaction of nitrosothiols is that where decomposition to nitric oxide occurs. 

The reaction in water at pH 7.4 has been much studied since the discovery of the importance of nitric oxide. The products are as for the thermal and photochemical reactions, except that the final product is nitrite ion. This is to be expected since nitric oxide in aerated water at pH 7.4 also yields quantitatively nitrite ion25, by it is believed the series of equations 7-9, which involves oxidation to nitrogen dioxide, further reaction to give dinitrogen trioxide which, in mildly alkaline solution, is hydrolysed to nitrite ion. Under anaerobic conditions it is possible to detect nitric oxide directly from the decomposition of nitrosothiols using a NO-probe electrode system26. Solutions of nitrosothiols both in... 

The physiological importance of nitric oxide should also be mentioned. It plays an important role in smooth muscle relaxation, platelet inhibition, neurotransmission, immune regulation, and penile erection (Nobel Prize in 1998 for the discovery of its role in the cardiovascular system). The importance of NO in biological systems stimulated the development of electrochemical sensors and the investigation of the electrochemical behavior of that compound. 

Murad, F. Discovery of some of the biological effects of nitric oxide and its role in cell signalling (Nobel lecture), Angew. Chem. Int. Ed. 1999, 38, 1856-1868. 

Furchgott RF (1996) The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA 276 1186-8... 

The discovery of the biological significance of nitric oxide (NO) in the mammalian systems stemmed from two lines of investigation that were conducted sqiait from each other. The first line was focused on the mechanism of acetylcholine-induced vascular relaxation in vitro and in vivo by the endothelium-derived relaxing factor, EDRF (Furchgott and Zawadzki, 1980), while the second examined the mechanism of macrophage cytotoxicity (Stuehr and Marietta, 1985 Hibbs et al, 1987). 

The nitrates act by releasing nitric oxide, which relaxes vascular smooth muscle. The discovery that endothelium-derived relaxing factor (EDRF) is nitric oxide (1) stimulated new interest in these drugs, as nitric oxide not only controls local vessel wall tension in response to shear stress, but also plays a role in regulating the interaction of platelets with blood vessel walls. The release of nitric oxide from the walls of atheromatous arteries is reduced, because of malfunctioning or absent endothelium. Atheromatous arteries behave differently from healthy arteries, in that these vessels vasoconstrict rather than vasodilate when stimulated by acetylcholine. This impairment of the acetylcholine vasomotor response appears to be related to serum cholesterol concentration (2). 

The discovery that the nitrosyl ligand is capable of binding to transition metals in two isomeric valence forms1 is one of the most dramatic recent developments in organometallic chemistry. Since bent NO donates 2 fewer electrons to the metal than the linear isomer does, linear-bent tautomerism raises the possibility of coordinative unsaturation and catalysis.2 In fact, complexes of nitric oxide are receiving increasing attention as catalysts,3 since they are more reactive than the corresponding carbonyls.4... 

The discovery of the biological role of nitric oxide has shed light on how nitroglycerin (C3H5N3O9)... 

The recent discovery that nitric oxide (NO) is a signaling molecule ubiquitous in tissue has raised the question that one of the pathways contributing to superoxide toxicity in vivo might be the formation of the highly reactive peroxynitrite anion (ONOO") produced by spontaneous reaction of NO with superoxide (77). It has been shown that perox5mitrite is a substrate of SOD (78). The interaction of SOD with peroxynitrite leads to a permanent modification of the enzyme at Tyr-108. The structural determination of the peroxynitrite-modified Cu2Zn2SOD has been conducted on monoclinic crystals (79). The structure confirms that peroxynitrite permanently modifies the Tyr-108 side chain with formation of 3-nitroty-rosine. The modification does not alter active site residues and the enzyme remains fully active. 

It is remarkable that only 7 years have passed since Palmer et al. (1987), Ignarro etal. (1987), and Furchgott (1988) published evidence that the bioactivity of nitric oxide (NO) was indistinguishable from that of endothelium-derived relaxing factor. This landmark discovery unleashed a torrent of research and fostered important expansions of our understanding of the control of vascular resistance, the biochemistry of immunity, the neurotransmitter function of NO, etc. (Moncada and Higgs, 1993). Pepke-Zaba et al. 

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