The reduction potential of nitric oxide (NO) and its importance to NO biochemistry

Abstract

A potential of about ؊0.8 (؎0.2) V (at 1 M versus normal hydrogen electrode) for the reduction of nitric oxide (NO) to its one-electron reduced species, nitroxyl anion ( 3 NO ؊ ) has been determined by a combination of quantum mechanical calculations, cyclic voltammetry measurements, and chemical reduction experiments. This value is in accord with some, but not the most commonly accepted, previous electrochemical measurements involving NO. Reduction of NO to 1 NO ؊ is highly unfavorable, with a predicted reduction potential of about ؊1.7 (؎0.2) V at 1 M versus normal hydrogen electrode. These results represent a substantial revision of the derived and widely cited values of ؉0.39 V and ؊0.35 V for the NO͞ 3 NO ؊ and NO͞ 1 NO ؊ couples, respectively, and provide support for previous measurements obtained by electrochemical and photoelectrochemical means. With such highly negative reduction potentials, NO is inert to reduction compared with physiological events that reduce molecular oxygen to superoxide. From these reduction potentials, the pKa of 3 NO ؊ has been reevaluated as 11.6 (؎3.4). Thus, nitroxyl exists almost exclusively in its protonated form, HNO, under physiological conditions. The singlet state of nitroxyl anion, 1 NO ؊ , is physiologically inaccessible. The significance of these potentials to physiological and pathophysiological processes involving NO and O 2 under reductive conditions is discussed. N itric oxide (NO) is an endogenously generated species with a diverse array of biological functions (1). NO is one of the primary regulators of vascular tone, is involved in signal transduction in both the peripheral and central nervous system, and is an integral part of the immune response system associated with macrophage and neutrophil activation. More recently, NO has been proposed to be involved in the regulation of mitochondrial function (2, 3). Problems in NO homeostasis have been implicated in the development of a variety of diseases and disorders such as hypertension and atherosclerosis (4), diabetes (5), and many neurodegenerative diseases (6). NO is also thought to be a cytoprotective agent, capable of inhibiting radical-induced damage and oxidative stress (7). To understand the actions of NO as a physiological messenger and a cytotoxic or cytoprotective effector molecule, it is essential to understand its basic chemical interactions with biological systems and its metabolic fate.NO and its reduced derivative NO Ϫ (and͞or its conjugate acid, HNO) have very different chemical properties and display distinct and often opposite effects in cells. For example, HNO͞ NO Ϫ has been found to be toxic under conditions where NO is cytoprotective (8). HNO͞NO Ϫ reacts with O 2 to generate potent oxidizing species, capable of damaging DNA and causing cellular thiol depletion, whereas NO does neither under similar conditions (9-11). HNO has been found to be a thiophilic electrophile (12), readily capable of modifying cellular thiol functions (13,14), whereas NO reacts only indirectly with thiols. HNO͞NO Ϫ h...

Comparison between the Geometric and Electronic Structures and Reactivities of {FeNO}7and {FeO2}8Complexes: A Density Functional Theory Study

“…However, a recent study by Fukuto, Houk, and co-workers on the reduction potential of the NO/NO -couple using a combination of experimental and computational methods indicated that NO is in fact more difficult to reduce than O 2 . 62 Hence, the main contribution to the observed differences in reactivity of Fe II toward NO and O 2 should be the difference in the strength of the resultant Fe III -NO -and Fe III -O 2 -bonds. In this study, spin-unrestricted DFT calculations with an experimentally optimized level of theory were used to analyze the relative reactivities of the 5C Fe II derivative of 1 toward NO and O 2 ( Figure 5).…”

Neuro-oxidative-nitrosative stress in sepsis

“…The reported E1 0 values have been obtained from Stanbury (1989); Koppenol et al (1992); Buettner (1993); and Bartberger et al (2002).…”

“…Therefore, iNOS is likely to enhance oxidative-nitrosative stress through the formation of ONOO À . ONOO À is much more reactive than NO (Table 1), causes tyrosine nitration and cysteine oxidation in various proteins (Radi et al, 1991), and decomposes to highly toxic free radicals, such as NO 2 K and K OH (Buettner, 1993;Bartberger et al, 2002). Cerebrospinal fluid levels of 3-nitrotyrosine have recently been found to be elevated in children with sepsis (Hamed et al, 2009); 3-nitrotyrosine, which is formed when a tyrosyl radical combines with NO 2 K during tyrosine nitration (Pacher et al, 2007), is relatively stable, and can thus be considered a surrogate molecular 'footprint' of nitrosative stress.…”

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

“…to proceed via reduction of NO • by SOD, [42] ferrocytochrome c, [43] and ubiquinol, [44] and/or reduction of GSNO by GSH and the alcohol dehydrogenase system. [45][46][47] Several groups have reported that HNO, per se a strong reductant, [48] can trigger reactions of oxidation.…”