Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bromates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed2001

The eosinophil peroxidase-hydrogen peroxide-bromide system of human eosinophils generates 5-bromouracil, a mutagenic thymine analogue.

Eosinophils use eosinophil peroxidase, hydrogen peroxide (H(2)O(2)), and bromide ion (Br(-)) to generate hypobromous acid (HOBr), a brominating intermediate. This potent oxidant may play a role in host defenses against invading parasites and eosinophil-mediated tissue damage. In this study, we explore the possibility that HOBr generated by eosinophil peroxidase might oxidize nucleic acids. When we exposed uracil, uridine, or deoxyuridine to reagent HOBr, each reaction mixture yielded a single major oxidation product that comigrated on reversed-phase HPLC with the corresponding authentic brominated pyrimidine. The eosinophil peroxidase-H(2)O(2)-Br(-) system also converted uracil into a single major oxidation product, and the yield was near-quantitative. Mass spectrometry, HPLC, UV--visible spectroscopy, and NMR spectroscopy identified the product as 5-bromouracil. Eosinophil peroxidase required H(2)O(2) and Br(-) to produce 5-bromouracil, implicating HOBr as an intermediate in the reaction. Primary and secondary bromamines also brominated uracil, suggesting that long-lived bromamines also might be physiologically relevant brominating intermediates. Human eosinophils used the eosinophil peroxidase-H(2)O(2)-Br(-) system to oxidize uracil. The product was identified as 5-bromouracil by mass spectrometry, HPLC, and UV--visible spectroscopy. Collectively, these results indicate that HOBr generated by eosinophil peroxidase oxidizes uracil to 5-bromouracil. Thymidine phosphorylase, a pyrimidine salvage enzyme, transforms 5-bromouracil to 5-bromodeoxyridine, a mutagenic analogue of thymidine. These findings raise the possibility that halogenated nucleobases generated by eosinophil peroxidase exert cytotoxic and mutagenic effects at eosinophil-rich sites of inflammation.

Bromates↗
PubMed2004

Kinetic analysis of the reactions of hypobromous acid with protein components: implications for cellular damage and use of 3-bromotyrosine as a marker of oxidative stress.

Hypohalous acids (HOX, X = Cl, Br) are produced by activated neutrophils, monocytes, eosinophils, and possibly macrophages. These oxidants react readily with biological molecules, with amino acids and proteins being major targets. Elevated levels of halogenated Tyr residues have been detected in proteins isolated from patients with atherosclerosis, asthma, and cystic fibrosis, implicating the production of HOX in these diseases. The quantitative significance of these findings requires knowledge of the kinetics of reaction of HOX with protein targets, and such data have not been previously available for HOBr. In this study, rate constants for reaction of HOBr with protein components have been determined. The second-order rate constants (22 degrees C, pH 7.4) for reaction with protein sites vary by 8 orders of magnitude and decrease in the order Cys > Trp approximately Met approximately His approximately alpha-amino > disulfide > Lys approximately Tyr >> Arg > backbone amides > Gln/Asn. For most residues HOBr reacts 30-100 fold faster than HOCl, though Cys and Met residues are approximately 10-fold less reactive, and ring halogenation of Tyr is approximately 5000-fold faster. Thus, Tyr residues are more, and Cys and Met much less, important targets for HOBr than HOCl. Kinetic models have been developed to predict the targets of HOX attack on proteins and free amino acids. Overall, these results shed light on the mechanisms of cell damage induced by HOX and indicate, for example, that the 3-chloro-Tyr:3-bromo-Tyr ratio does not reflect the relative roles of HOCl and HOBr in disease processes.

Amides↗
PubMed1996

Inactivation of vanadium bromoperoxidase: formation of 2-oxohistidine.

The basis of the irreversible inactivation of the vanadium bromoperoxidase (V-BrPO) isolated from the marine alga Ascophyllum nodosum under turnover conditions at low pH (i.e., 15 to 100 mM H2O2, 0.1 KBr, ca. 15 nM V-BrPO in 0.1 M citrate, pH 4) has been investigated. Inactivation under these conditions was found to produce 2-oxohistidine as identified by HPLC using electrochemical detection. Formation of 2-oxohistidine requires all the components of turnover (i.e., bromide, hydrogen peroxide, and V-BrPO) as well as low pH; inactivation does not occur nor is significant 2-oxohistidine formed in the presence of hydrogen peroxide alone. The oxidation of histidine did not occur by singlet oxygen generated by V-BrPO, because neither 2-oxohistidine nor inactivation occur under the conditions in which singlet oxygen is produced quantitatively by V-BrPO. The addition of aqueous bromine to N alpha-benzoylhistidine at low pH formed N alpha-benzoyl-2-oxohistidine. cis-Dioxovanadium(V) (VO2+) in strong acid and MoO(O2)2(ox)2- (ox2- is oxalate) at pH 5, both of which are functional mimics of V-BrPO by oxidizing bromide by hydrogen peroxide, catalyzed the oxidation of N alpha-benzoylhistidine to N alpha-benzoyl-2-oxohistidine. Furthermore, when hypobromite was added to N alpha-benzoylhistidine in the presence of hydrogen peroxide at neutral pH, conditions under which HOBr would react first with H2O2 to produce singlet oxygen, no N alpha-benzoyl-2-oxohistidine was formed. Thus the oxidation of histidine in V-BrPO is proposed to occur via oxidized bromine species. Irreversible inactivation V-BrPO was also found to be accompanied by release of vanadium.

Bromates↗
PubMed2000

Activated leukocytes oxidatively damage DNA, RNA, and the nucleotide pool through halide-dependent formation of hydroxyl radical.

A variety of chronic inflammatory conditions are associated with an increased risk for the development of cancer. Because of the numerous links between DNA oxidative damage and carcinogenesis, a potential role for leukocyte-generated oxidants in these processes has been suggested. In the present study, we demonstrate a novel free transition metal ion-independent mechanism for hydroxyl radical ((*)OH)-mediated damage of cellular DNA, RNA, and cytosolic nucleotides by activated neutrophils and eosinophils. The mechanism involves reaction of peroxidase-generated hypohalous acid (HOCl or HOBr) with intracellular superoxide (O(2)(*)(-)) forming (*)OH, a reactive oxidant species implicated in carcinogenesis. Incubation of DNA with either isolated myeloperoxidase (MPO) or eosinophil peroxidase (EPO), plasma levels of halides (Cl(-) and Br(-)), and a cell-free O(2)(*)(-) -generating system resulted in DNA oxidative damage. Formation of 8-hydroxyguanine (8-OHG), a mutagenic base which is a marker for (*)OH-mediated DNA damage, required peroxidase and halides and occurred in the presence of transition metal chelators (DTPA +/- desferrioxamine), and was inhibited by catalase, superoxide dismutase (SOD), and scavengers of hypohalous acids. Similarly, exposure of DNA to either neutrophils or eosinophils activated in media containing metal ion chelators resulted in 8-OHG formation through a pathway that was blocked by peroxidase inhibitors, hypohalous acid scavengers, and catalytically active (but not heat-inactivated) catalase and SOD. Formation of 8-OHG in target cells (HA1 fibroblasts) occurred in all guanyl nucleotide-containing pools examined following exposure to both a low continuous flux of HOCl (at sublethal doses, as assessed by [(14)C]adenine release and clonogenic survival), and hyperoxia (to enhance intracellular O(2)(*)(-) levels). Mitochondrial DNA, poly A RNA, and the cytosolic nucleotide pool were the primary targets for oxidation. Moreover, modest but statistically significant increases in the 8-OHG content of nuclear DNA were also noted. These results suggest that the peroxidase-H(2)O(2)-halide system of leukocytes is a potential mechanism contributing to the well-established link between chronic inflammation, DNA damage, and cancer development.

Animals↗
PubMed2002

Enantiomerically pure alpha-amino acid synthesis via hydroboration-suzuki cross-coupling.

The Garner aldehyde-derived methylene alkene 5 and the corresponding benzyloxycarbonyl compound 25 undergo hydroboration with 9-BBN-H followed by palladium-catalyzed Suzuki coupling reactions with aryl and vinyl halides. After one-pot hydrolysis-oxidation, a range of known and novel nonproteinogenic amino acids were isolated as their N-protected derivatives. These novel organoborane homoalanine anion equivalents are generated and transformed under mild conditions and with wide functional group tolerance: electron-rich and -poor aromatic iodides and bromides (and a vinyl bromide) all undergo efficient Suzuki coupling. The extension of this methodology to prepare meso-DAP, R,R-DAP, and R,R-DAS is also described.

Amino Acids↗
PubMed2005

Propagation of photosensitive chemical waves on the circular routes.

The propagation of chemical waves in the photosensitive Belousov-Zhabotinsky (BZ) reaction was investigated using an excitable field in the shape of a circular ring or figure "8" that was drawn by computer software and then projected on a film soaked with BZ solution using a liquid-crystal projector. For a chemical wave in a circular reaction field, the shape of the chemical wave was investigated depending on the ratio of the inner and outer radii. When two chemical waves were generated on a field shaped like a figure "8" (one chemical wave in each circle) as the initial condition, the location of the collision of the waves either was constant or alternated depending on the degree of overlap of the two circular rings. These experimental results were analyzed on the basis of a geometrical discussion and theoretically reproduced on the basis of a reaction-diffusion system using a modified Oregonator model. These results suggest that the photosensitive BZ reaction may be useful for creating spatio-temporal patterns depending on the geometric arrangement of excitable fields.

2,2'-Dipyridyl↗
PubMed2006

Uptake of SO2 on HOBr-ice surfaces.

The uptake of SO2 on HOBr-treated ice surfaces has been studied using a flow reactor coupled with a differentially pumped quadrupole mass spectrometer at 190-240 K. The initial uptake coefficient was determined as a function of HOBr surface coverage, theta(HOBr), on the ice. The uptake coefficients increase as the HOBr coverage increases. The uptake coefficient can be expressed as gamma(t) = k(h)theta(HOBr), where k(h) = 1.5 x 10(-19) molecules(-1) cm(-2) at 191 K and k(h) = 6.4 x 10(-21) molecules(-1) cm(-2) at 210 K and theta(HOBr) is in the range of 8 x 10(13) to 1.2 x 10(15) molecules cm(-2). The effects of temperature and film thickness on the uptake coefficients of SO2 by the HOBr-treated ice films were also studied. The activation energy E(a) of SO(2) on HOBr-ice surfaces is approximately -81 +/- 8 kJ/mol in the 190-215 K range. Kinetic results were interpreted in terms of the Eley-Rideal mechanism. This study suggests that the uptake of SO2 on ice/snow surfaces is enhanced by the presence of HOBr near the ice surface. The implication for atmospheric chemistry is that HOBr-ice surfaces may not provide a significant pathway to oxide S(IV) in the boundary layer due to both lower uptake coefficient and smaller HOBr surface coverage at T > 220 K.

Bromates↗
PubMed2006

Interactive propagation of photosensitive chemical waves on two circular routes.

The propagation of chemical waves in the photosensitive Belousov-Zhabotinsky (BZ) reaction was investigated using an excitable field composed of two rings in slight contact, which were drawn using computer software and then projected on a film soaked with BZ solution using a liquid-crystal projector. When the initial phase difference between the two chemical waves in the individual rings was smaller than a critical value, this initial value was maintained after collision of the chemical waves. However, when the initial phase difference was larger than this critical value, the phase difference converged to the same value after the second collision. The critical value increased with an increase in the thickness of the rings. These experimental results on the geometry of the excitable field are discussed in relation to the nature of chemical wave propagation. These results suggest that the photosensitive BZ reaction may be useful for creating spatiotemporal patterns that depend on the geometric arrangement of excitable fields.

2,2'-Dipyridyl↗
PubMed2006

Heterogeneous reactions of SO2 with HOCl and HOBr on ice surfaces.

The heterogeneous reactions of SO2 + HOX (X = Cl or Br) --> products on ice surfaces at low temperature have been investigated in a flow reactor coupled with a differentially pumped quadrupole mass spectrometer. Pseudo-first-order loss of SO2 over the ice surfaces has been measured under the conditions of concurrent HOX flow. The initial uptake coefficient of SO2 reaction with HOX has been determined as a function of HOX surface coverage, theta(HOX), on the ice. The initial uptake coefficients increase as the HOX coverage increases. The uptake coefficient can be expressed as gamma(t) = k(h)theta(HOX), where k(h) is an overall rate constant of SO2 + HOCl, which was determined to be (2.3 +/- 0.6) x 10(-19) and (1.7 +/- 0.5) x 10(-19) molecules(-1) x cm2 at 190 and 210 K, and k(h) of SO2 + HOBr is (6.1 +/- 2.0) x 10(-18) molecules(-1) x cm2 at 190 K. theta( HOX) is in the range 8.1 x 10(13)-9.1 x 10(14) molecules x cm(-2). The kinetic results of the heterogeneous reaction of SO2 + HOX on ice surface are interpreted using the Eley-Rideal mechanism. The activation energy of the heterogeneous reaction of SO2 with HOCl on ice surface was determined to be about -37 +/- 10 kJ/mol in the 190-238 K range.

Bromates↗
PubMed2006

Reaction mechanism of uracil bromination by HBrO: a new way to generate the enol-keto form of 5-bromouracil.

Knowledge on the uracil bromination reaction is helpful for understanding the origin of the mutagenicity of 5-bromouracil (BrU). To get more details about this reaction, we explore the corresponding reaction mechanism by theoretical method. A total of seven pathways were studied for this purpose. The diketo form of BrU is observed as the main product in these pathways, which agrees well with experimental results. The most energy-favorable reaction pathway is found to be that Br and OH attacked the opposite sides of uracil. The reaction intermediate reported in the experiment is predicted to be reasonably stable. In the following step, a dehydration process occurs between H11 and O13-H14 when there are no explicit H(2)O taking part. However, when there are explicit water molecules in the environment, explicit H(2)O will lower the reaction barrier in the formation of reaction intermediates and the final product BrU. A proton-transfer process from C5 to O10 is facilitated by explicit H(2)O, which results in enol-keto form intermediate of this modified base (defined as BrU*). These results indicate a new way to generate the enol-keto form of BrU.

Bromates↗
PubMed2004

Microelectrochemical approach to induce local cell adhesion and growth on substrates.

The nature of an albumin-coated substrate that blocks protein adsorption and cell adhesion was rapidly switched to cell-adhesive by exposure to an oxidizing agent such as HBrO. This finding has enabled cellular pattern drawing even on a single-cell level by closely scanning a microelectrode above the substrate and electrochemically producing the agent at the tip of the electrode. The present microelectrochemical cell patterning is applicable even for a previously cell-patterned substrate and for a grooved substrate. These unique technical features will have impacts on a variety of cell-based studies that require the analysis of heterotypic cell-cell interactions and cellular arrangement on an uneven surface such as semiconductor devices.

Bromates↗
PubMed2005

The role of aromatic amino acid oxidation, protein unfolding, and aggregation in the hypobromous acid-induced inactivation of trypsin inhibitor and lysozyme.

Hypobromous acid (HOBr) generated by activated eosinophils has been implicated in tissue injury observed in asthma, allergic reactions, and some infections. Proteins are major targets for this oxidant, but the mechanisms by which HOBr induces loss of function are not well-established. In this study, we have examined the effect of HOBr on protein structure (as assessed by amino acid loss, side chain oxidation, fragmentation, aggregation, and unfolding) and activity of a model protease inhibitor, soybean trypsin inhibitor (STI), and the protective enzyme lysozyme. Exposure of both proteins to low oxidant concentrations (< or = 5-fold molar excess) results in loss of function. In each case, loss of activity is associated with the selective oxidation of His, Trp, and Tyr residues, which results in protein unfolding (with lysozyme) and protein aggregation (with STI). Reaction with these residues accounts for 25 and 50% of the HOBr with STI (25-fold excess) and lysozyme (4-fold excess), respectively. These processes are believed to lead to changes in the structure of the proteins, which disrupts substrate binding. With both proteins, the oxidation of other residues, including Met, does not appear to play a major role. Bromamines, formed by reaction with amine groups, are major products, which account for 45 and 35% of the HOBr with STI (25-fold excess) and lysozyme (4-fold excess), respectively. Decomposition of these species correlates with secondary oxidation reactions, and with lysozyme, a time-dependent loss in activity. Overall, 70% of the HOBr can be accounted for with STI and 95% with lysozyme.

Amino Acids, Aromatic↗
PubMed2006

Thiocyanate is an efficient endogenous scavenger of the phagocytic killing agent hypobromous acid.

Second-order rate constants for the reaction of HOBr/OBr- (a putative killing agent of eosinophils and a reactive oxygen species that is implicated in mutagenesis and in human inflammatory diseases) with SCN- (an endogenous species in human physiologic fluids) are determined by stopped-flow spectroscopy. The proposed mechanism includes parallel pathways with Br+ transfer to SCN- by general acid catalysis and by direct reaction with HOBr. HOBr reacts with SCN- with a second-order rate constant (2.3 x 10(9) M(-1) s(-1)) that is 2 orders of magnitude larger than that previously measured for the reaction of HOCl with SCN- (2.3 x 10(7) M(-1) s(-1)), and very close to the diffusion limit. In contrast to OCl-, OBr- exhibits a measurable rate of reaction with SCN- (3.8 x 10(4) M(-1) s(-1)). On a molar basis, SCN- is the most effective scavenger of HOBr to be reported to date (200 times more effective than cysteine and 650 times more effective than methionine). Computational models suggest that SCN- is competitive with respect to other scavengers at physiologically relevant concentrations, which leads us to propose it may limit the lifetime of HOBr and its propensity to inflict host tissue damage during inflammatory response, especially during eosinophilia. Furthermore, the product of the nonenzymatic reaction of HOBr and SCN-, hypothiocyanite (OSCN-), is an effective antimicrobial that is relatively innocuous toward mammalian cell lines. Since one of the principal charges of eosinophil cells is to clear extracellular parasites via nonphagocytic mechanisms that involve degranulation of eosinophil peroxidase (EPO, the principal mammalian enzyme that produces HOBr), a larger role for OSCN- is suggested for parasitic infection.

Bromates↗
PubMed2006

New functions of XPC in the protection of human skin cells from oxidative damage.

Xeroderma pigmentosum (XP) C is involved in the recognition of a variety of bulky DNA-distorting lesions in nucleotide excision repair. Here, we show that XPC plays an unexpected and multifaceted role in cell protection from oxidative DNA damage. XP-C primary keratinocytes and fibroblasts are hypersensitive to the killing effects of DNA-oxidizing agents and this effect is reverted by expression of wild-type XPC. Upon oxidant exposure, XP-C primary keratinocytes and fibroblasts accumulate 8,5'-cyclopurine 2'-deoxynucleosides in their DNA, indicating that XPC is involved in their removal. In the absence of XPC, a decrease in the repair rate of 8-hydroxyguanine (8-OH-Gua) is also observed. We demonstrate that XPC-HR23B complex acts as cofactor in base excision repair of 8-OH-Gua, by stimulating the activity of its specific DNA glycosylase OGG1. In vitro experiments suggest that the mechanism involved is a combination of increased loading and turnover of OGG1 by XPC-HR23B complex. The accumulation of endogenous oxidative DNA damage might contribute to increased skin cancer risk and account for internal cancers reported for XP-C patients.

Bromates↗
PubMed2003

Combined application of organozinc chemistry and one-pot hydroboration-Suzuki coupling to the synthesis of amino acids.

Hydroboration using 9-BBN-H of the protected enantiomerically pure but-3-enylglycine derivative 11, prepared by copper-catalysed allylation of the serine-derived organozinc reagent 1, followed by Suzuki coupling of the derived borane with a variety of aromatic halides, 2-bromopyridine and 2-bromopropene gives the protected amino acids 14a-l and 15. This method augments our previous methods for the synthesis of phenylalanine homologues.

Amino Acids↗
PubMed2006

Kinetics and mechanism of the reaction of [RuIII(edta)(H2O)]- with HOBr to form an intermediate RuV=O complex in aqueous solution.

The interaction of [Ru(III)(edta)(H(2)O)](-) (1) (edta = ethylenediaminetetraacetate) with the oxygen transfer agent HOBr, was studied kinetically as a function of [HOBr] and temperature (5-35 degrees C) at a fixed pH of 6.2. Spectroscopic evidence is reported for the formation of a high valent intermediate (edta)Ru(V)=O complex. Water soluble 2,2'-azobis(3-ethylbenzithiazoline-6-sulfonate) (ABTS) was employed as a trap for this intermediate in order to gain further mechanistic information. Reactions were carried out under pseudo-first conditions for [ABTS] >> [HOBr] >> [1], and were monitored as a function of time for the formation of the one-electron oxidation product ABTS(*+). The reported kinetic data are interpreted in terms of a suggested reaction mechanism and discussed in reference to data reported before.

Bromates↗
PubMed2007

Degradation of extracellular matrix and its components by hypobromous acid.

EPO (eosinophil peroxidase) and MPO (myeloperoxidase) are highly basic haem enzymes that can catalyse the production of HOBr (hypobromous acid). They are released extracellularly by activated leucocytes and their binding to the polyanionic glycosa-minoglycan components of extracellular matrix (proteoglycans and hyaluronan) may localize the production of HOBr to these materials. It is shown in the present paper that the reaction of HOBr with glycosaminoglycans (heparan sulfate, heparin, chondroitin sulfate and hyaluronan) generates polymer-derived N-bromo derivatives (bromamines, dibromamines, N-bromosulfon-amides and bromamides). Decomposition of these species, which can occur spontaneously and/or via one-electron reduction by low-valent transition metal ions (Cu+ and Fe2+), results in polymer fragmentation and modification. One-electron reduction of the N-bromo derivatives generates radicals that have been detected by EPR spin trapping. The species detected are consistent with metal ion-dependent polymer fragmentation and modification being initiated by the formation of nitrogen-centred (aminyl, N-bromoaminyl, sulfonamidyl and amidyl) radicals. Previous studies have shown that the reaction of HOBr with proteins generates N-bromo derivatives and results in fragmentation of the polypeptide backbone. The reaction of HOBr with extracellular matrix synthesized by smooth muscle cells in vitro induces the release of carbohydrate and protein components in a time-dependent manner, which is consistent with fragmentation of these materials via the formation of N-bromo derivatives. The degradation of extracellular matrix glycosaminoglycans and proteins by HOBr may contribute to tissue damage associated with inflammatory diseases such as asthma.

Animals↗
PubMed1998

Comparison of human red cell lysis by hypochlorous and hypobromous acids: insights into the mechanism of lysis.

Human red blood cells are lysed by the neutrophil-derived oxidant hypochlorous acid (HOCl), although the mechanism of lysis is unknown. Hypobromous acid (HOBr), a similarly reactive oxidant, lysed red cells approx. 10-fold faster than HOCl. Therefore we compared the effects of these oxidants on thiols, membrane lipids and proteins to determine which reactions are associated with lysis. There was no difference in the loss of reduced glutathione or membrane thiols with either oxidant, but HOBr reacted more readily with membrane lipids and proteins. Bromohydrin derivatives of phospholipids and cholesterol were seen at approx. one-tenth the level of oxidant than chlorohydrins were. However, these products were detected only with high concentrations of HOCl or HOBr, which caused instant haemolysis. Membrane protein modification occurred at much lower doses of oxidant and was more closely correlated with lysis. SDS/PAGE analysis showed that band 3, the anion transport protein, was lost at the lowest dose of HOBr and at the higher concentrations of HOCl. Labelling the red cells with eosin 5-maleimide, a fluorescent label for band 3, suggested possible clustering of this protein in oxidant-exposed cells. There was also irreversible cross-linking of all the major membrane proteins; this reaction occurred more readily with HOBr. The results indicate that membrane protein modification is the reaction responsible for HOCl-mediated lysis. These effects, and particularly cross-link formation, might result in clustering of band 3 and other membrane and cytoskeletal proteins to form haemolytic pores.

Anion Exchange Protein 1, Erythrocyte↗