Kinetic study of the formation of <i>N</i>‐chloramines

Antelo, Juan; Arce, F.; Parajó, M.

doi:10.1002/kin.550270703

Cited by 44 publications

(29 citation statements)

References 9 publications

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“…It was concluded from the observed pH reaction profiles that the acid (HOCl), rather than the hypochlorite anion ( − OCl), is more reactive, and that with Cys as the target, the thiol anion (RCH 2 S − ) is the more reactive species [49]. This group has also studied the reactions of HOCl with various amines at different pH values, and concluded that − OCl is more reactive than the acid (HOCl), and reacts most readily with protonated amine groups (RNH 3 + ) [47,48,77,79]. This results in maximal reaction rates at pH values that are the average of the pK a values for HOCl and the amine (usually pH ~ 8.5).…”

Section: Kinetics Of Hocl Reactionsmentioning

confidence: 95%

“…The kinetics of reactions of HOCl with amino acid sidechains and other protein targets have been studied in some detail, both by competitive kinetic studies and stopped flow methods [13,47,49,54,57,[75][76][77][78]. Many of the early studies of HOCl reaction kinetics focused on amine groups, particularly the simplest amine, ammonia, and were undertaken in acidic (pH 2.5-6) or basic (pH [10][11][12][13] solutions.…”

Section: Kinetics Of Hocl Reactionsmentioning

confidence: 99%

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Reactions of Myeloperoxidase-Derived Oxidants with Biological Substrates:Gaining Chemical Insight into Human Inflammatory Diseases

Pattison

Davies

2006

CMC

320

266

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The heme enzyme myeloperoxidase (MPO) is released at sites of inflammation by activated leukocytes. A key function of MPO is the production of hypohalous acids (HOX, X = Cl, Br) which are strong oxidants with potent antibacterial properties. However, HOX can also damage host tissue when produced at the wrong place, time or concentration; this has been implicated in several human diseases. Thus, elevated blood and leukocyte levels of MPO are significant independent risk factors for atherosclerosis, and specific markers of HOX-mediated protein oxidation are often present at elevated levels in patients with inflammatory diseases (e.g. asthma). HOX react readily with amino acids, proteins, carbohydrates, lipids, nucleobases and antioxidants. Sulfur-containing amino acids (Cys, Met, cystine) and amines on amino acids, nucleobases, sugars and lipids are the major targets for HOX. Reaction with amines generates chloramines (RNHCl) and bromamines (RNHBr), which are more selective oxidants than HOX and are key intermediates in HOX biochemistry. As these and other products of MPO-derived oxidants are unstable, understanding the role of HOX-induced damage in disease cannot be obtained solely by stable product analysis, and knowledge of the reaction kinetics is essential. This review collates kinetic and product data for HOX, chloramine and bromamine reactions with biological substrates. It highlights how kinetic data may be used to predict the effect of HOX-mediated oxidation on complex biological targets, such as lipoproteins and extracellular matrix in atherosclerosis, or protein-DNA complexes in cancer, thereby providing a basis for unraveling the mechanisms by which these oxidants generate biological damage.

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Section: Kinetics Of Hocl Reactionsmentioning

confidence: 95%

Section: Kinetics Of Hocl Reactionsmentioning

confidence: 99%

Reactions of Myeloperoxidase-Derived Oxidants with Biological Substrates:Gaining Chemical Insight into Human Inflammatory Diseases

Pattison

Davies

2006

CMC

320

266

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“…With GlcNH 2 (1-5 mM; 1 mM HOCl) under analogous conditions, a rapid loss of the − OCl peak (within 30 s) and formation of a peak with λ max 258 nm (Supplementary Figure 1E, inset, at http://www.BiochemJ.org/bj/391/bj3910125add.htm) were detected. Rate constants for reaction at 22 and 37 • C ( Table 2) were estimated using the Arrhenius equation with an activation energy (E a ) of 43 kJ · mol −1 ; the latter value is the experimentally determined E a for the reaction of HOCl with 2-propylamine [33], a close structural analogue of the GlcNH 2 -derived amine function. As the kinetic data obtained were limited by the dead time of the stopped-flow system at these temperatures, experiments were carried out at 9.5 • C to slow the reaction down.…”

Section: Rate Constants For Reaction Of Hocl With Glycosamine Monosacmentioning

confidence: 99%

Oxidation of heparan sulphate by hypochlorite: role of N-chloro derivatives and dichloramine-dependent fragmentation

Rees

Pattison

Davies

2005

Biochemical Journal

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Activated phagocytes release the haem enzyme MPO (myeloperoxidase) and produce superoxide radicals and H2O2 via an oxidative burst. MPO uses H2O2 and Cl- to form HOCl, the physiological mixture of hypochlorous acid and its anion present at pH 7.4. As MPO binds to glycosaminoglycans, oxidation of extracellular matrix and cell surfaces by HOCl may be localized to these materials. However, the reactions of HOCl with glycosaminoglycans are poorly characterized. The GlcNAc (N-acetylglucosamine), GlcNSO3 (glucosamine-N-sulphate) and GlcNH2 [(N-unsubstituted) glucosamine] residues of heparan sulphate are potential targets for HOCl. It is shown here that HOCl reacts with each of these residues to generate N-chloro derivatives, and the absolute rate constants for these reactions have been determined. Reaction at GlcNH2 residues yields chloramines and, subsequently, dichloramines with markedly slower rates, k2 approximately 3.1x10(5) and 9 M(-1) x s(-1) (at 37 degrees C) respectively. Reaction at GlcNSO3 and GlcNAc residues yields N-chlorosulphonamides and chloramides with k2 approximately 0.05 and 0.01 M(-1) x s(-1) (at 37 degrees C) respectively. The corresponding monosaccharides display a similar pattern of reactivity. Decay of the polymer-derived chloramines, N-chlorosulphonamides and chloramides is slow at 37 degrees C and does not result in major structural changes. In contrast, dichloramine decay is rapid at 37 degrees C and results in fragmentation of the polymer backbone. Computational modelling of the reaction of HOCl with heparan sulphate proteoglycans (glypican-1 and perlecan) predicts that the GlcNH2 residues of heparan sulphate are major sites of attack. These results suggest that HOCl may be an important mediator of damage to glycosaminoglycans and proteoglycans at inflammatory foci.

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“…Excellent correlations between rate constants and nucleophile basicity have previously been reported for the N-halogenation of amines and amino acids by sodium hypochlorite 6,7 or sodium hypobromite 14 and for several other chemically controlled reactions involving chloronium ion transfer, such as the reactions of chloramines with amines, amino acids and peptides 15,16 and the oxidation of iodide, 17 bromide, 18 cyanide, 19 nitrite 20 or sulphite 21 by hypochlorous acid or N-chloramines, which involve nucleophilic attack on the chlorine, followed by cleavage of the Cl-O bond and the loss of an OH group. In every case where the reaction is not diffusion controlled, the rate constant increases with increasing basicity of the amino group of the substrate.…”

Section: Mechanism and Discussionmentioning

confidence: 69%

“…This behaviour departs markedly from that of similar reactions where sodium hypochlorite was used as the halogenating reagent. 6,7 In order to clarify the mechanism of this type of reaction, in this work we carried out a kinetic study of the formation of N-chloro compounds by use of NCS as the halogenating reagent.…”

Section: Introductionmentioning

confidence: 99%

Kinetic study of the chlorine transfer fromN-chlorosuccinimide to amino compounds

Antelo

Arce

Crugeir

et al. 1997

J. Phys. Org. Chem.

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A kinetic study of the reactions of N-chlorosuccinimide (NCS) with glycine (Gly), sarcosine (Sar), 2-methylalanine (2MA), proline (Pro) and pyrrolidine (Pyr) was carried out. The reactions were found to be first order with respect to both NCS and the amine or amino acid and order ؊ 1 in proton concentration. In order to calculate the experimental activation parameters, the effect of temperature on the reaction rates was studied. The ionic strength and buffer concentration were found to have no effect on the rate constant. A reaction mechanism involving Cl + transfer from NCS to the amine or amino acid to form an N-chloro compound is proposed. ©

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Kinetic study of the formation of N‐chloramines

Abstract: We studied the kinetics of the chlorination of amines by sodium hypochlorite in strongly alkaline aqueous solution. A reaction mechanism compatible with experimental results is proposed and discussed. o 1995

Cited by 44 publications

References 9 publications

Reactions of Myeloperoxidase-Derived Oxidants with Biological Substrates:Gaining Chemical Insight into Human Inflammatory Diseases

Reactions of Myeloperoxidase-Derived Oxidants with Biological Substrates:Gaining Chemical Insight into Human Inflammatory Diseases

Oxidation of heparan sulphate by hypochlorite: role of N-chloro derivatives and dichloramine-dependent fragmentation

Kinetic study of the chlorine transfer fromN-chlorosuccinimide to amino compounds

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