DOCSLIB.ORG

Regulation of Protein Function by S-Nitrosation and S-Glutathionylation: Processes and Targets in Cardiovascular Pathophysiology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Regulation of Protein Function by S-Nitrosation and S-Glutathionylation: Processes and Targets in Cardiovascular Pathophysiology View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio della Ricerca - Università di Pisa Biol. Chem. 2017; 398(12): 1267–1293 Review Eugenia Belcastro, Caroline Gaucher, Alessandro Corti, Pierre Leroy, Isabelle Lartaud and Alfonso Pompella* Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology https://doi.org/10.1515/hsz-2017-0150 aims to provide an update of available knowledge in the Received April 26, 2017; accepted August 7, 2017; previously field, with a special focus on the respective (sometimes published online August 19, 2017 competing and antagonistic) roles played by protein S-nitrosations and S-thionylations in biochemical and cel- Abstract: Decades of chemical, biochemical and patho- lular processes specifically pertaining to pathogenesis of physiological research have established the relevance cardiovascular diseases. of post-translational protein modifications induced by processes related to oxidative stress, with critical reflec- Keywords: cardiovascular diseases; glutathione; mixed tions on cellular signal transduction pathways. A great disulfides; nitric oxide; RNS; ROS; S-glutathionylation; deal of the so-called ‘redox regulation’ of cell function is S-nitrosation. in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific ami- noacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues Introduction have received most attention, due to the critical roles they The role of nitric oxide (NO) in several signaling routes play in determining the structure/function correlates in has been clearly established (Grisham et al., 1999; Pacher proteins. The peculiar reactivity of these residues results et al., 2007). NO, one of the most important substances in two major classes of modifications, with incorpora- produced by the endothelium, plays a key role in home- tion of NO moieties (S-nitrosation, leading to formation ostasis maintenance and has gained recognition as a of protein S-nitrosothiols) or binding of low molecular crucial modulator in vascular pathophysiology. NO has weight thiols (S-thionylation, i.e. in particular S-glutath- a number of intracellular effects, e.g. vasorelaxation, ionylation, S-cysteinylglycinylation and S-cysteinylation). endothelial regeneration, inhibition of leukocyte chemo- A wide array of proteins have been thus analyzed in detail taxis, and platelet adhesion. The physiological chemistry as far as their susceptibility to either modification or both, of NO is complex, for it encompasses numerous potential and the resulting functional changes have been described reactions. Increasing attention has been paid to its ability in a number of experimental settings. The present review to produce covalent post-translational protein modifi- cations, and among these, the modification of cysteine *Corresponding author: Alfonso Pompella, Department of residues has received more attention due to the functional Translational Research NTMS, University of Pisa Medical School, Via relevance of many of them. The cysteine thiol may be modi- Roma 55, I-56126 Pisa, Italy, e-mail: [email protected] fied by incorporation of a NO moiety (S-nitrosation) or of a Eugenia Belcastro: CITHEFOR EA3452 “Drug targets, formulation glutathione moiety (S-glutathionylation). Both modifica- and preclinical assessment”, Faculté de Pharmacie, Université de Lorraine, 5 rue Albert Lebrun, BP 80403, F-54001 Nancy Cedex, tions may ensue from different reactions induced by nitric France; and Department of Translational Research NTMS, University oxide-related species, especially S-nitrosoglutathione of Pisa Medical School, Via Roma 55, I-56126 Pisa, Italy (GSNO). GSNO is one of the most important intracellular Caroline Gaucher, Pierre Leroy and Isabelle Lartaud: CITHEFOR S-nitrosothiols (Martínez-Ruiz and Lamas, 2007), and as EA3452 “Drug targets, formulation and preclinical assessment”, will be detailed below, a number of studies have investi- Faculté de Pharmacie, Université de Lorraine, 5 rue Albert Lebrun, BP 80403, F-54001 Nancy Cedex, France gated its potential use as a therapeutic agent in selected Alessandro Corti: Department of Translational Research NTMS, conditions, including cardiovascular dideases (Hornyák University of Pisa Medical School, Via Roma 55, I-56126 Pisa, Italy et al., 2011). Brought to you by | Universita di Pisa Authenticated Download Date | 3/27/19 1:01 PM 1268 E. Belcastro et al.: S-nitrosation and S-glutathionylation in cardiovascular pathophysiology In the present review, the first part will focus on the soluble guanylyl cyclase (sGC), producing increased con- role of NO as a signaling molecule, by analyzing the main centrations of cyclic guanosine monophosphate (cGMP). post-translational modifications (PTMs) it can induce in Cyclic GMP interacts with three types of intracellular pro- cellular proteins. The second part will explore the simi- teins: cGMP-dependent protein kinases (PKGs), cGMP-reg- larities, differences and commonalities between the pro- ulated ion channels, and cGMP-regulated cyclic nucleotide cesses of protein S-nitrosation and S-glutathionylation. phosphodiesterases (PDEs). Thus, cGMP can alter cell In fact, both modifications share many mechanistic and function through mechanisms dependent or independent functional features, making them solid candidates as of protein phosphorylation. Depending on the sites of NO general mechanisms for intracellular signal transduc- release and cGMP activation, different biological effects tion. Finally, the third section will focus on the identifi- can be observed. In vascular smooth muscle cells (VSMCs), cation of proteins individually modified by S-nitrosation increased cyclic GMP concentrations will activate cGMP- and S-gluthathionylation. The most abundant protein dependent kinases capable of decreasing intracellular thiol is the free cysteine of albumin, which makes of this calcium, thus producing relaxation (Moncada et al., 1991), abundant protein an inevitable target of both processes. whereas increased cGMP in platelets will decrease platelet S-nitrosylation of albumin has been recognized since the activation and adhesion to the surface of the endothelium beginning as a mechanism involved in the bioactivity of (Radomski and Moncada, 1993). endothelium-derived NO, at that time denoted as EDRF Conversely, the activation of iNOS, induced during (Stamler et al., 1992; Keaney et al., 1993). Our review will pathophysiological processes such as inflammation, pro- be focused on the resulting effects of these PTMs on other duces much higher concentrations of NO (>1 μm). iNOS protein targets critical in cardiovascular pathophysiology. is expressed physiologically, but is induced by certain The competition of the two processes on the same protein inflammatory cytokines (IL-1, INFγ, TNF-α), LPS and oxi- targets will also be discussed, taking into account the dual dizing agents. The effects of NO will depend on the site of ability of GSNO to both S-nitrosate as well as S-glutathio- its formation, concentrations achieved, as well as the type nylate proteins. of targeted tissue. Generally, modulation of protein function by NO can occur through three main reactions: 1. Nitrosylation, a reversible coordination of NO to tran- NO signaling in the cardiovascular sition metal ions in enzymes, such as ferrous (Fe2+) system heme prosthetic groups within the sGC enzyme, lead- ing to enzyme activation and increased formation of NO is a gaseous radical with a short half-life, continuously c G M P. synthesized from L-arginine by the nitric oxide synthase 2. Protein nitrosation, with formation of a covalent bond (NOS) (Palmer et al., 1988). There are three distinct iso- between NO and cysteine (S-nitrosation) or tryptophan forms of NOS that differ in structure and function (Stuehr, (N-nitrosation) residues. Modifications of free cysteine 1997). Endothelial NOS (eNOS) and neuronal NOS (nNOS) residues present at active sites of effector proteins and are constitutively expressed and are referred as Ca2+- peptides will change the activity or function of these dependent enzymes (Ayajiki et al., 1996) and generate proteins. This configures a mode of post-translational small amounts of NO for signaling. The third type is the protein modification as important as phosphorylation inducible isoform (iNOS), Ca2+-independent and inducible (Lima, 2010; Heikal, 2011). A number of studies have by immunological stimuli (Schulz et al., 1992). This latter focused on the mechanistic aspects of protein nitro- is activated in response to inflammation and generates sation (see e.g. Wolhuter and Eaton, 2017), however high amounts of NO (Knowles and Moncada, 1994). it has been shown that de-nitrosation reactions also From a functional point of view, NO acts as a chemical play critical roles in the control of nitrosated proteins messenger particularly in vascular and immune systems, levels as well as of NO release. In the specific case of where it participates in the regulation of a wide range of S-nitrosation, the formed S-nitrosothiols (RSNOs) can physiological processes. Its production within the cell is undergo spontaneous or assisted trans-nitrosations, finely adjusted to ensure appropriate effects. Indeed, in resulting in the transfer of the NO moiety from high physiological conditions, the low concentrations of NO molecular weight (protein) thiols
Load more

Recommended publications
  • Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics
    Review Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics Joel Mintz 1,†, Anastasia Vedenko 2,†, Omar Rosete 3 , Khushi Shah 4, Gabriella Goldstein 5 , Joshua M. Hare 2,6,7 , Ranjith Ramasamy 3,6,* and Himanshu Arora 2,3,6,* 1 Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Davie, FL 33328, USA; [email protected] 2 John P Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; [email protected] (A.V.); [email protected] (J.M.H.) 3 Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA; [email protected] 4 College of Arts and Sciences, University of Miami, Miami, FL 33146, USA; [email protected] 5 College of Health Professions and Sciences, University of Central Florida, Orlando, FL 32816, USA; [email protected] 6 The Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA 7 Department of Medicine, Cardiology Division, Miller School of Medicine, University of Miami, Miami, FL 33136, USA * Correspondence: [email protected] (R.R.); [email protected] (H.A.) † These authors contributed equally to this work. Abstract: Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumori- Citation: Mintz, J.; Vedenko, A.; genic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the Rosete, O.; Shah, K.; Goldstein, G.; level of production, the oxidative/reductive (redox) environment in which this radical is generated, Hare, J.M; Ramasamy, R.; Arora, H.
    [Show full text]
  • Mechanisms of Nitric Oxide Reactions Mediated by Biologically Relevant Metal Centers
    Struct Bond (2014) 154: 99–136 DOI: 10.1007/430_2013_117 # Springer-Verlag Berlin Heidelberg 2013 Published online: 5 October 2013 Mechanisms of Nitric Oxide Reactions Mediated by Biologically Relevant Metal Centers Peter C. Ford, Jose Clayston Melo Pereira, and Katrina M. Miranda Abstract Here, we present an overview of mechanisms relevant to the formation and several key reactions of nitric oxide (nitrogen monoxide) complexes with biologically relevant metal centers. The focus will be largely on iron and copper complexes. We will discuss the applications of both thermal and photochemical methodologies for investigating such reactions quantitatively. Keywords Copper Á Heme models Á Hemes Á Iron Á Metalloproteins Á Nitric oxide Contents 1 Introduction .................................................................................. 101 2 Metal-Nitrosyl Bonding ..................................................................... 101 3 How Does the Coordinated Nitrosyl Affect the Metal Center? .. .. .. .. .. .. .. .. .. .. .. 104 4 The Formation and Decay of Metal Nitrosyls ............................................. 107 4.1 Some General Considerations ........................................................ 107 4.2 Rates of NO Reactions with Hemes and Heme Models ............................. 110 4.3 Mechanistic Studies of NO “On” and “Off” Reactions with Hemes and Heme Models ................................................................................. 115 4.4 Non-Heme Iron Complexes ..........................................................
    [Show full text]
  • Nitrosamines EMEA-H-A5(3)-1490
    25 June 2020 EMA/369136/2020 Committee for Medicinal Products for Human Use (CHMP) Assessment report Procedure under Article 5(3) of Regulation EC (No) 726/2004 Nitrosamine impurities in human medicinal products Procedure number: EMEA/H/A-5(3)/1490 Note: Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. Table of contents Table of contents ...................................................................................... 2 1. Information on the procedure ............................................................... 7 2. Scientific discussion .............................................................................. 7 2.1. Introduction......................................................................................................... 7 2.2. Quality and safety aspects ..................................................................................... 7 2.2.1. Root causes for presence of N-nitrosamines in medicinal products and measures to mitigate them............................................................................................................. 8 2.2.2. Presence and formation of N-nitrosamines
    [Show full text]
  • A Nitric Oxide/Cysteine Interaction Mediates the Activation of Soluble Guanylate Cyclase
    A nitric oxide/cysteine interaction mediates the activation of soluble guanylate cyclase Nathaniel B. Fernhoffa,1, Emily R. Derbyshirea,1,2, and Michael A. Marlettaa,b,c,3 Departments of aMolecular and Cell Biology and bChemistry, University of California, Berkeley, CA 94720; and cCalifornia Institute for Quantitative Biosciences and Division of Physical Biosciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 Contributed by Michael A. Marletta, October 1, 2009 (sent for review August 22, 2009) Nitric oxide (NO) regulates a number of essential physiological pro- high activity of the xsNO state rapidly reverts to the low activity of cesses by activating soluble guanylate cyclase (sGC) to produce the the 1-NO state. Thus, all three sGC states (basal, 1-NO, and xsNO) second messenger cGMP. The mechanism of NO sensing was previ- can be prepared and studied in vitro (7, 8). Importantly, these ously thought to result exclusively from NO binding to the sGC heme; results define two different states of purified sGC with heme bound however, recent studies indicate that heme-bound NO only partially NO (7, 8), one with a high activity and one with a low activity. activates sGC and additional NO is involved in the mechanism of Further evidence for a non-heme NO binding site was obtained maximal NO activation. Furthermore, thiol oxidation of sGC cysteines by blocking the heme site with the tight-binding ligand butyl results in the loss of enzyme activity. Herein the role of cysteines in isocyanide, and then showing that NO still activated the enzyme NO-stimulated sGC activity investigated. We find that the thiol mod- (14).
    [Show full text]
  • Accelerating Effect of Ascorbic Acid on A/-Nitrosamine Formation and Nitrosation by Oxyhyponitrite1
    [CANCER RESEARCH 39, 3871-3874, October 1979] 0008-5472/79/0039-OOOOS02.00 Accelerating Effect of Ascorbic Acid on A/-Nitrosamine Formation and Nitrosation by Oxyhyponitrite1 Shaw-Kong Chang,2 George W. Harrington,5 Marc Rothstein,3 William A. Shergalis,4 Daniel Swern, and Saroj K. Vohra. Department of Chemistry, Temple University. Philadelphia. Pennsylvania 19122, and the Fels Research Institute. Temple University, Philadelphia. Pennsylvania 19140 ABSTRACT ments to be made readily during the initial and intermediate stages of reaction. DPP as used in this study avoids this The reaction of nitrite ion with ascorbic acid and its effect on difficulty and allows reactions to be studied in situ, yielding the rate of nitrosation of secondary amines have been investi interesting results. The use of DPP as an analytical method for gated by differential pulse polarography in aqueous acidic A/-nitrosamines and as a technique to study some of the chem solution. Ascorbic acid shows nonuniform behavior: it accel istry of W-nitrosamines has been previously reported by us (6- erates the nitrosation of N-methylaniline between pH 1.00 and 8, 31, 32). 1.95, allows the nitrosation of diphenylamine and iminodiace- tonitrile, but inhibits the nitrosation of secondary amines, such MATERIALS AND METHODS as dimethylamine, diethylamine, proline, hydroxyproline, N- methylaminoacetonitrile, N-methylaminopropionitrile, and sar- Instrumentation. The instrumentation, cells, and conditions cosine. The nitrosating agent generated by the reaction be used for DPP and spectral studies have been previously de tween ascorbic acid and nitrite ion appears to be oxyhyponitrite scribed (6, 7). The pH was measured with a Leeds & Northrup ion (N2CV2).
    [Show full text]
  • Does N-Nitrosomelatonin Compete with S-Nitrosothiols As a Long
    nalytic A al & B y i tr o Singh et al., Biochem Anal Biochem 2016, 5:1 s c i h e m m Biochemistry & e DOI: 10.4172/2161-1009.1000262 i h s c t r o i y B ISSN: 2161-1009 Analytical Biochemistry Commentary Open Access Does N-Nitrosomelatonin Compete with S-Nitrosothiols as a Long Distance Nitric Oxide Carrier in Plants? Neha Singh, Harmeet Kaur, Sunita Yadav and Satich C Bhatla* Laboratory of Plant Physiology and Biochemistry, Department of Botany, University of Delhi, India Plants transmit a variety of signaling molecules from roots to of proteins [13]. aerial parts, and vice-versa, in response to their growth conditions Determination of GSNO in plant samples still presents a (environment, nutrients, stress factors etc.). A signaling molecule challenge due to several technical obstacles and cumbersome sample should be produced quickly, induce a defined effect within the cell preparation procedures. It can also be affected by light, metal-catalyzed and be removed or metabolized rapidly when not required. Nitric SNO decomposition, enzymatic degradation catalyzed by GSNO oxide (NO) plays significant signaling roles in plant cells since it has reductase, and a reduction in the S-NO bond caused by reductants and all the above-stated features. It is a gaseous free radical, can gain or endogenous thiols [13]. Two different approaches to detect GSNO have lose an electron, has short half-life ( ̴ 30 sec) and it can exist in three been reported in higher plants: immunohistochemical analysis using interchangeable forms, namely the radical (NO•), the nitrosonium commercial antibodies against GSNO and liquid chromatography- cation (NO+) and as nitroxyl radical (NO).
    [Show full text]
  • II.1.8 Alkyl Nitrites by Yasuo Seto
    1.8 II.1.8 Alkyl nitrites by Yasuo Seto Introduction Alkyl nitrites are highly volatile organic solvents of aliphatic alcohol esters of nitrites [1]. Amyl nitritea, butyl nitrite and isobutyl nitrite are the representative alkyl nitrites; their boiling points are 98, 78 and 67 °C, respectively. Amyl nitrite is being widely used as a detoxicant for cyanide poisoning, because alkyl nitrites oxidize hemoglobin in erythrocytes to yield methemogloblin, which is bound with cyanide to inactivate it [1]. Alkyl nitrites also show a coronary artery-di- lating eff ect, and had been, therefore, used for the treatment of angina pectoris many years ago [2]; the pharmacological eff ect of the dilation of the coronary arteries was found due to the action of nitrogen monoxide produced by decomposition of alkyl nitrites [3]. Th ey are being mainly used as materials for manufacturing drugs or as reagents for synthesis in industries; they are also used as aromatics. Because of their pharmacological eff ect, alkyl nitrites are being abused as uncontrolled inhalant drugs and causing a social problem [4]. Although there are many reports on toxic and fatal cases due to alkyl nitrites [5], reports on their fatal doses are few; it is estimated that oral ingestion of 10–15 mL of each alkyl nitrite causes serious methe- moglobinemia [6]. Th e LD50 value for an alkyl nitrite is reported to be 205 mg/kg. Th ere are not many cases of analysis of alkyl nitrites in the fi eld of forensic toxicology. In this chapter, the methods for analysis of the compounds by headspace (HS)-gas chromatography (GC) and liquid-liquid extraction-GC are presented.
    [Show full text]
  • Non-Canonical Chemical Feedback Self-Limits Nitric Oxide-Cyclic GMP Signaling in Health and Disease Vu Thao-Vi Dao1,2,9, Mahmoud H
    www.nature.com/scientificreports OPEN Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease Vu Thao-Vi Dao1,2,9, Mahmoud H. Elbatreek1,3,9 ✉ , Martin Deile4, Pavel I. Nedvetsky5, Andreas Güldner6, César Ibarra-Alvarado7, Axel Gödecke8 & Harald H. H. W. Schmidt1 ✉ Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted, for example, in pulmonary hypertension. Its dysregulation in disease is incompletely understood. Here we show in pulmonary artery endothelial cells that feedback inhibition by NO of the NO receptor, the cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous NO from endothelial NO synthase and exogenous NO from NO donor compounds decreased sGC protein and activity. This efect was not mediated by cGMP as the NO-independent sGC stimulator, or direct activation of cGMP- dependent protein kinase did not mimic it. Thiol-sensitive mechanisms were also not involved as the thiol-reducing agent N-acetyl-L-cysteine did not prevent this feedback. Instead, both in-vitro and in- vivo and in health and acute respiratory lung disease, chronically elevated NO led to the inactivation and degradation of sGC while leaving the heme-free isoform, apo-sGC, intact or even increasing its levels. Thus, NO regulates sGC in a bimodal manner, acutely stimulating and chronically inhibiting, as part of self-limiting direct feedback that is cGMP independent. In high NO disease conditions, this is aggravated but can be functionally recovered in a mechanism-based manner by apo-sGC activators that re-establish cGMP formation. Te nitric oxide (NO)-cGMP signaling pathway plays several essential roles in physiology, including cardio- pulmonary homeostasis1,2.
    [Show full text]
  • Nitrite and Nitrosyl Compounds in Food Preservation
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1411 (1999) 475^488 Review Nitrite and nitrosyl compounds in food preservation Richard Cammack a;*, C.L. Joannou 1;a, Xiao-Yuan Cui 2;a, Claudia Torres Martinez 3;b, Shaun R. Maraj b, Martin N. Hughes b a Division of Life Sciences, King's College, London W8 7AH, UK b Department of Chemistry, King's College, London WC2R 2LS, UK Received 27 August 1998; received in revised form 2 November 1998; accepted 16 December 1998 Abstract Nitrite is consumed in the diet, through vegetables and drinking water. It is also added to meat products as a preservative. The potential risks of this practice are balanced against the unique protective effect against toxin-forming bacteria such as Clostridium botulinum. The chemistry of nitrite, and compounds derived from it, in food systems and bacterial cells are complex. It is known that the bactericidal species is not nitrite itself, but a compound or compounds derived from it during 3 food preparation. Of a range of nitrosyl compounds tested, the anion of Roussin's black salt [Fe4S3(NO)7] was the most inhibitory to C. sporogenes. This compound is active against both anaerobic and aerobic food-spoilage bacteria, while some other compounds are selective, indicating multiple sites of action. There are numerous possible targets for inhibition in the bacterial cells, including respiratory chains, iron^sulfur proteins and other metalloproteins, membranes and the genetic apparatus. ß 1999 Elsevier Science B.V. All rights reserved. Keywords: Roussin's salts; Nitrosothiol; Electron paramagnetic resonance spectroscopy; (Clostridium botulinum); (Listeria monocytogenes) Contents 1.
    [Show full text]
  • Continuous-Flow Production of Alkyl Nitrites, Originally Designed by BIOS Chemicals
    FLOW CHEMISTRY Industry Perspective ● Peer reviewed Jean-Christophe M. Continuous-flow production Monbaliu of alkyl nitrites JEAN-CHRISTOPHE M. MONBALIU1*, JEREMY JORDA2, BÉRENGÈRE CHEVALIER2, CHRISTIAN V. STEVENS1, BERNARD MORVAN3 *Corresponding author 1. Ghent University, SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Coupure links 653, Gent, B-9000, Belgium 2. CORNING S.A.S, Corning European Technology Center, Avenue de Valvins 7 bis, Avon, F-77210, France 3. BIOS Chemicals, Plateforme technologique DELTA Sud, Verniolle, F- 09340, France the oxidation of olefins (6f, 7c). Recent publications reported ABSTRACT their use for the production of diazonium intermediates in the Alkyl nitrites are important building blocks for the chemical continuous production of synthesis of azo dyes (6c). and pharmaceutical industries. In this article, we report a case study for the continuous-flow production of alkyl nitrites, originally designed by BIOS Chemicals. The PREPARATION OF ALKYL NITRITES intrinsic advantages of a Corning® Advanced-Flow™ reactor system, including high versatility, high mixing, and Numerous methods have been developed at the lab scale heat-exchange efficiency under corrosive conditions, for preparing alkyl nitrites from alcohols: esterification with allowed the development of an economically viable and nitrous acid; transesterification from tert-butyl nitrite (8a) or from user-friendly process in a short period of time, leading to N-nitrosoamines (8b); and nitrosation with various nitrosating a throughput of 10t/year of processed material with high agents such as nitrosyl chloride (8c). Thiols and trimethylsilyl ethers purity (93-98 percent). can also be transformed in the corresponding nitrites (8d). Industrial processes can be divided into two categories: (a) 50 liquid phase processes and (b) vapour phase processes.
    [Show full text]
  • Focusing of Nitric Oxide Mediated Nitrosation and Oxidative Nitrosylation As a Consequence of Reaction with Superoxide
    Focusing of nitric oxide mediated nitrosation and oxidative nitrosylation as a consequence of reaction with superoxide Michael G. Espey*, Douglas D. Thomas, Katrina M. Miranda, and David A. Wink Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Edited by Louis J. Ignarro, University of California, Los Angeles School of Medicine, Los Angeles, CA, and approved May 29, 2002 (received for review March 18, 2002) The impact of nitric oxide (NO) synthesis on different biological oxidative nitrosylation dependent mechanisms, which are strongly Ϫ cascades can rapidly change dependent on the rate of NO formation influenced by the relative rates of NO and O2 formation. and composition of the surrounding milieu. With this perspective, we used diaminonaphthalene (DAN) and diaminofluorescein (DAF) to Methods ؊ Ϫ examine the nitrosative chemistry derived from NO and superoxide Generation of O2 and NO. Formation of O from conversion of ؊ 2 (O2 ) simultaneously generated at nanomolar to low micromolar per hypoxanthine (HX, 500 ␮M; Sigma) to xanthine was catalyzed by minute rates by spermine͞NO decomposition and xanthine oxidase- xanthine oxidase (XO; Roche; ref. 29) in PBS (pH 7.4, 37°C) catalyzed oxidation of hypoxanthine, respectively. Fluorescent tria- containing the metal chelator diethylenetriaminepentaacetic acid Ϫ zole product formation from DAN and DAF increased as the ratio of (DTPA, 50 ␮M; Sigma). The rate of O formation by stock enzyme ؊ ؊ 2 O2 to NO approached equimolar, then decreased precipitously as O2 was assessed by cytochrome c reduction (Sigma; 570 nm, ␧ ϭ 21,000 exceeded NO. This pattern was also evident in DAF-loaded MCF-7 MϪ1⅐cmϪ1; ref.
    [Show full text]
  • Synthetic Uses of S-Nitrosothiols in Organic Chemistry
    SYNTHETIC USES OF S-NITROSOTHIOLS IN ORGANIC CHEMISTRY By TYLER DAVID BIGGS A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY WASHINGTON STATE UNIVERSITY Department of Chemistry MAY 2017 © Copyright by TYLER DAVID BIGGS, 2017 All Rights Reserved © Copyright by TYLER DAVID BIGGS, 2017 All Rights Reserved To the Faculty of Washington State University: The members of the Committee appointed to examine the dissertation of TYLER DAVID BIGGS find it satisfactory and recommend that it be accepted. Ming Xian, Ph.D., Chair Cliff E. Berkman, Ph.D. Aurora Clark, Ph.D. Jeffery Jones, Ph.D. ii ACKNOWLEDGMENT I would like to thank Dr. Ming Xian for his supervision, help, and guidance over the course of my Ph.D. study. His challenges and questions kept me on track, and forced me to constantly reevaluate myself critically. I would also like to thank Dr. Ronald for helping to kindle my interest and passion in chemistry. I would like to thank my committee members for sharing their time and knowl- edge. I would also like to thank the Washington State University Chemistry depart- ment for the resources and equipment provided, and those in the front office who keep things running. Finally I would like to thank my fellow students who have supported me. Ryan Joseph, for his help and enthusiasm in chemistry and LATEX. Nelmi Devarie, for talks of cooking and science. Laksiri, Hua Wang, and Chung-Min Park for their help in training me in the basics. Most importantly are my family and friends, with out their support I would have never started this journey, or have a place to go up on finishing it, without their help and commitment.
    [Show full text]