Showing papers on "Cyanide published in 1984"

Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria.

Abstract: Publisher Summary The determination of the rate of O 2 - production is based upon the spectrophotometric measurement of oxidation or reduction reactions in which O 2 - is a reactant. The concentration of the spectrophotometric indicator that reacts with O 2 - is adjusted to compete effectively with the spontaneous dismutation of O 2 - so that nearly all O 2 - produced can be detected. The involvement of O 2 - is ascertained by the use of superoxide dismutase that inhibits the reaction rate specifically due to O 2 - . Cyanide, which is often used as inhibitor of the mitochondrial cytochrome oxidase ( K i about 3 x 10 -5 M) is also an inhibitor of the often used copper-containing superoxide dismutase ( K i about 3 × 10 -4 M). It is possible to use enough cyanide that partially inhibits cytochrome oxidase without inhibiting superoxide dismutase. Alternatively, bacterial or mitochondrial (manganese-containing) superoxide dismutase can be used. Mitochondria have Mn-superoxide dismutase in the matrix space, so to measure the total production of O 2 - by mitochondrial membranes, the dismutase should be inhibited or removed. Because effective inhibitors of Mn-superoxide dismutase are not known, matrical superoxide dismutase is usually removed by the repetitive washing of submitochondrial particles obtained by sonication or by other means. Mitochondrial O 2 - production is pH dependent and increases toward the alkaline region.

Cyanide intoxication and its mechanism of antagonism

Abstract: The biological studies on cyanide are unique in that they preceded the chemical preparation of the substance (1). The last comprehensive review on the pharma­ cology and toxicology of cyanide was written by Dr. Reid Hunt at Johns Hopkins University in 1923 (2); however, this review was written in German. Recently, other books and monographs on cyanide have appeared (3, 4). The present review is restricted to selected aspects of cyanide and is primarily concerned with a descriptive and interpretive appraisal of the status of cyanide intoxication and its mechanism of antagonism. Cyanide bas created complex problems for modem society and these prob­ lems have evolved not only from industrial pollution but, paradoxically, from an inadvertent attempt to resolve pollution problems (5). Its use as a suicidal, homicidal, chemical warfare, and genocidal agent is well known. Toxic prob­ lems have been associated with ingesting cyanide-containing foods, and occu­ pational hazards have arisen as the industrial use of cyanide has increased. In medicine, it has created problems because some drugs with nitrile moieties liberate cyanide. Much of the toxicological interest in cyanide has focused on its rapid lethal action; however, its most widely distributed toxicologic problems are due to its chronic toxicity from dietary, industrial, and environmental factors. Cyanide is not wholly a toxin synthesized by civilization, as it existed in prebiotic times and was involved in biogenesis. In addition, cyanide is produced by various organisms and plants in our environment and has a role in normal metabolism.

Clinical Pharmacokinetics of Nitroprusside, Cyanide, Thiosulphate and Thiocyanate

Abstract: Sodium nitroprusside decomposes within a few minutes after intravenous infusion to form metabolites which are pharmacologically inactive but toxicologically important. Free cyanide, which represents 44% w/w of the sodium nitroprusside molar mass, is formed and must be detoxified in the body into thiocyanate using thisulphate as substrate. Nitroprusside penetrates cell membranes slowly. At therapeutic dose levels its distribution is probably mainly extracellular. Contact with the sulfhydryl groups in the cell walls, however, immediately initiates breakdown of the molecule. Sodium nitroprusside taken orally is not absorbed from the gastrointestinal tract to any appreciable extent. Cyanides in the body form prussic acid, which can rapidly penetrate mucous and cell membranes. In the blood, about 99% of the prussic acid binds to the methaemoglobin of erythrocytes. At normal physiological levels, however, the total body methaemoglobin of an adult human can only bind about 10mg of prussic acid; this is a small fraction of the amounts usually infused therapeutically as sodium nitroprusside. The endogenous detoxification of prussic acid exhibits zero-order kinetics. The limiting factor is a sulphur donor, principally thiosulphate, which is available in the body in only limited amounts. The rate of spontaneous detoxification of prussic acid in humans is only about 1 microgram/kg/min, corresponding to a sodium nitroprusside infusion of about 2 microgram/kg/min. This dose limit set by the prussic acid toxicity of sodium nitroprusside can, however, be increased considerably by simultaneous infusion of thiosulphate. A lack of thiosulphate can be detected early by a rise of the prussic acid concentration in the erythrocytes. Thiosulphate taken orally is not absorbed by the body. After intravenous infusion, its serum half-life is about 15 minutes. Most of the thiosulphate is oxidised to sulphate or is incorporated into endogenous sulphur compounds; a small proportion is excreted through the kidneys. Thiocyanate taken orally is completely absorbed by the body. In healthy persons its volume of distribution is approximately 0.25 L/kg and the serum half-life about 3 days; elimination is mainly renal. Thiocyanate toxicity does not represent a serious therapeutic problem with intravenous infusion of sodium nitroprusside.

Electrocatalytic oxidation and determination of arsenic(III) on a glassy carbon electrode modified with a thin film of mixed-valent ruthenium(III, II) cyanide

Abstract: Le courant de pic voltammetrique a balayage lineaire obtenu est directement proportionnel a la concentration en As(III) dans le domaine 5 μM-2 mM avec une limite de detection de 3,5 μM

A re-examination of the reactions of cyanide with cytochrome c oxidase

Abstract: Experiments were performed to examine the cyanide-binding properties of resting and pulsed cytochrome c oxidase in both their stable and transient turnover states. Inhibition of the oxidation of ferrocytochrome c was monitored as a function of cyanide concentration. Cyanide binding to partially reduced forms produced by mixing cytochrome c oxidase with sodium dithionite was also examined. A model is presented that accounts fully for cyanide inhibition of the enzyme, the essential feature of which is the rapid, tight, binding of cyanide to transient, partially reduced, forms of the enzyme populated during turnover. Computer fitting of the experimentally obtained data to the kinetic predictions given by this model indicate that the cyanide-sensitive form of the enzyme binds the ligand with combination constants in excess of 10(6) M-1 X s-1 and with KD values of 50 nM or less. Kinetic difference spectra indicate that cyanide binds to oxidized cytochrome a33+ and that this occurs rapidly only when cytochrome a and CuA are reduced.

Photodegradation of sodium nitroprusside: biologic activity and cyanide release.

Abstract: Because the belief that cyanide is released from nitroprusside in vivo recently was challenged, the authors performed a series of experiments that examined the conditions under which nitroprusside is degraded. These experiments include an examination of the release of cyanide and nitric oxide from nitroprusside in vitro, the release of cyanide in vivo, and a comparison of the biologic activity of intact and degraded nitroprusside. Nitroprusside in aqueous solution degraded when exposed to white or blue light but not to red light. While light at 20 microW X cm-2 produced 40% apparent photodegradation after 6 h exposure, while white light at 220 microW X cm-2 produced 100% apparent photodegradation after 2 h exposure. At 10% apparent photodegradation, 10% of the nitrosyl ligand was recovered as free nitric oxide, and 0.4% of the cyanide ligand was recovered as free cyanide. Following a 2-h infusion of light-protected nitroprusside in seven patients, cyanide concentrations ranged from 1.4 to 45.5 microM and 0.09 to 3.2 microM in blood and plasma, respectively. These values were not changed by exposing the samples to white light (220 microW X cm-2) for 4 h. Intact and photodegraded nitroprusside produced identical hypotensive responses in rats as would be expected, since the nitrosyl ligand was detected in solution following degradation, and it mediates this action. Cyanide was released from nitroprusside, both on its exposure to light in vitro and also in vivo. The latter was not an artifact of the assay for cyanide. Nitroprusside releases cyanide in vivo, and cyanide toxicity is a true complication of its use.

Studies on the mechanism of acute toxicity of nitriles in mice.

Abstract: Acute toxicity and metabolism of 21 nitriles in mice were studied in relation to their chemical structures. All the test nitriles liberated cyanide ions both in vivo and in vitro, with the exception of benzonitrile , although the extent of liberation and the effect of carbon tetrachloride (CCl4) pretreatment on the mortality of animals differed among nitriles. From these results, test compounds were tentatively divided into three groups. In group 1 (13 compounds), acute toxicity was greatly reduced by CCl4 pretreatment, in group 2 (seven compounds), toxicity was not significantly changed or was somewhat enhanced, and in group 3, benzonitrile only, toxicity was clearly enhanced. The amount of cyanide was higher (0.68-0.80 microgram CN/g brain) at death in the brains of mice given group-1 compounds, the level being comparable to that found in mice killed by dosing with potassium cyanide. After oral doses of each nitrile, the time course for cyanide levels in the liver varied among the compounds. The difference between group-1 and -2 compounds lay in the dose-cyanide liberation relationship in liver, and in the kinetics for cyanide liberation in the hepatic microsomal enzyme system. Double-reciprocal plots of enzyme activity showed a linear relationship for nitriles of group 1 and a non-linear one for group 2. The relationship between log (1/LD50) and log P for the compounds in group 1 fitted a parabolic plot, while that for compounds in group 2 was linear.

The absorption of gold cyanide onto activated carbon. III. Factors influencing the rate of loading and the equilibrium capacity

Abstract: The results are reported of experiments on the influence of a number of variables on the rate of loading of gold cyanide onto activated carbon and the equilibrium capacity of the carbon. These variables include the concentrations of gold and free cyanide in solution, the pH value and ionic strength of the solution, the concentration of organic compounds in the solution, the temperature, the particle size of the carbon, and the mixing efficiency. The experiments were carried out under approximately steady-state conditions to simulate the conditions in a countercurrent carbon-in-pulp absorption plant. In addition, the results are reported of experiments to establish whether the absorption of gold cyanide onto activated carbon is a reversible process.

Formation and reduction of a 'peroxy' intermediate of cytochrome c oxidase by hydrogen peroxide.

Abstract: In the presence of micromolar concentrations of H2O2, ferric cytochrome c oxidase forms a stable complex characterized by an increased absorption intensity at 606-607 nm with a weaker absorption band in the 560-580 nm region. Higher (millimolar) concentrations of H2O2 result in an enzyme exhibiting a Soret band at 427 nm and an alpha-band of increased intensity in the 589-610 nm region. Addition of H2O2 to ferric cytochrome c oxidase in the presence of cyanide results in absorbance increases at 444nm and 605nm. These changes are not seen if H2O2 is added to the cyanide complex of the ferric enzyme. The results support the idea that direct reaction of H2O2 with ferric cytochrome a 3 produces a ‘peroxy’ intermediate that is susceptible to further reduction by H2O2 at higher peroxide concentrations. Electron flow through cytochrome a is not involved, and the final product of the reaction is the so-called ‘pulsed’ or ‘oxygenated’ ferric form of the enzyme.

Catalysis of an isotopic exchange between CO2 and the carboxyl group of acetate by Methanosarcina barkeri grown on acetate

Abstract: Cell suspensions of Methanosarcina barkeri (strain Fusaro) grown on acetate were found to catalyze the formation of methane and CO2 from acetate (30–40 nmol/min·mg protein) and an isotopic exchange between the carboxyl group of acetate and 14CO2 (30–40 nmol/min·mg protein). An isotopic exchange between [14C]-formate and acetate was not observed. Cells grown on methanol mediated neither methane formation from acetate nor the exchange reactions. The data indicate that the isotopic exchange between CO2 and the carboxyl group of acetate is a partial reaction of methanogenesis from acetate. Both reactions were completely inhibited by low concentrations of cyanide (20 μM) or of hydrogen (0.5% in the gas phase). Methane formation from acetate was also completely inhibited by low concentrations of carbon monoxide (0.2% in the gas phase) whereas only significantly higher concentrations of CO had an effect on the exchange reaction. In the concentration range tested KCN, H2 and CO had no effect on methane formation from methanol or from H2 and CO2; however, cyanide (20 μM) also affected methane formation from CO. The results are discussed with respect to proposed mechanisms of methane and CO2 formation from acetate.

Intoxication by cyanide in fires: a study in monkeys using polyacrylonitrile

Abstract: It is suspected that hydrogen cyanide (HCN) may be an important factor in incapacitating fire victims, but the effects of sublethal exposures are not well characterized. Also, the incapacitating effects of fire atmospheres result from exposure to a mixture of toxic products so that the contribution from each component is difficult to determine. The mechanisms of incapacitation in monkeys exposed to the pyrolysis products of polyacrylonitrile (PAN) were compared to those resulting from low level HCN gas exposures. The physiological effects of the PAN atmospheres were almost identical to those of HCN gas alone. They consisted of hyperventilation, followed by loss of consciousness after 1-5 min, bradycardia with arrhythmias and T-wave abnormalities, and were followed by a rapid recovery after exposure. Hydrogen cyanide is considered to be the major toxic product formed by the pyrolysis of PAN. It is suggested that HCN may produce rapid incapacitation at low blood levels of cyanide in fires, while death may occur later due to carbon monoxide poisoning or other factors.

Autotrophic synthesis of activated acetic acid from two CO2 inMethanobacterium thermoautotrophicum

Abstract: Autotrophic CO2 fixation byMethanobacterium thermoautotrophicum proceeds via a total synthesis of activated acetic acid. The origins of the individual carbon atoms were studied in vitro and in vivo. The experiments described showed: (1) Two different routes of CO2 reduction lead to the individual carbon positions in acetate. (2) The carboxyl carbon is provided by a cyanide-sensitive enzyme which reduces CO2 to a bound intermediate with the oxidation state of CO. This intermediate can be supplied by gaseous CO rather than by formate, when its synthesis from CO2 is blocked by cyanide. The characteristics of the enzymic reaction are those of carbon monoxide dehydrogenase. (3) The methyl carbon is derived from CO2 via a different cyanide-insensitive CO2 reduction path, which probably shares the initial intermediates of methanogenesis from CO2 and H2. It does not involve methyl coenzyme M. It is concluded that the pathway of autotrophic CO2 assimilation into activated acetic acid inMethanobacterium is mechanistically related to the clostridial total acetate synthesis.

Cyanide inhibition of cytochrome c oxidase. A rapid-freeze e.p.r. investigation

Abstract: The inhibition of cytochrome c oxidase by cyanide, starting either with the resting or the pulsed enzyme, was studied by rapid-freeze quenching followed by quantitative e.p.r. It is found that a partial reduction of cytochrome oxidase by transfer of 2 electron equivalents from ferrocytochrome c to cytochrome a and CuA will induce a transition from a closed to an open enzyme conformation, rendering the cytochrome a3-CuB site accessible for cyanide binding, possibly as a bridging ligand. A heterogeneity in the enzyme is observed in that an e.p.r. signal from the cytochrome a3 3+-HCN complex is only found in 20% of the molecules, whereas the remaining cyanide-bound a3-CuB sites are e.p.r.-silent.

Complementary analytical methods for cyanide, sulphide, certain transition metals and lanthanides in ion chromatography

Abstract: Conventional ion chromatography excludes the analyses of anionic species with pK > 7, and transition metals that can form hydroxide precipitates at neutral pH. These limitations come from the combined characteristics of the suppressor column and the electrical conductivity detector. By suitable selection of the detection system, an extension of analytical limits can be achieved. For fast and accurate analyses of cyanide and sulphide ions, with an electrochemical method involving a silver sulphide based ion-selective electrode and a high pH buffered eluent, the detection limit can reach the p.p.b. level. For determinations of transition and rare earth metal ions, a spectrophotometric detection system is proposed. By post-column mixing with the colour-forming reagents PAR and Arsenazo I, respectively, transition metal and rare earth metal ions can be monitored by measuring the absorbance at 498 and 600 nm. The detection limit can reach the 0.1 p.p.m. level with good precision. The working principle and reaction mechanism of the proposed methods are also discussed in detail.

The extraction of gold from cyanide solutions by strong- and weak-base anion-exchange resins

Abstract: This paper descriptionbes the extraction of gold, as the anionic aurocyanide complex, from solution by strong- and weakbase anion-exchange resins. The effects, on the rate of extraction and the loading capacity for gold, of parameters such as pH, temperature, ionic strength, agitation, and the presence of competing anions are reported. The elution and regeneration of strong- and weak-base resins will be examined in a second paper. A third paper in this series will present the results of several small-scale pilot-plant investigations carried out with strong- and weakbase resins In cyanide pulps from various South African gold mines, and will compare the metallurgical performance of resin-In-pulp with that of the carbon-in-pulp process.

Observations on various silyl-cuprate reagents

Abstract: The mixed silyl-cuprate reagent (6), made from 1 equiv. of methyl-lithium, 1 equiv. of phenyldimethylsilyl-lithium, and 1 equiv. of copper(I) cyanide, reacts with 3-methylcyclohexenone (7), with methyl cinnamate (9), with 1-vinylcyclohexyl acetate (11), and with hex-1-yne (13) to transfer, in each case, the silyl group, and to give the β-silylcarbonyl compounds (8) and (10), the allylsilane (12), and the vinylsilane (14), without the concomitant formation of involatile silicon-containing by-products. The silyl-cuprate reagent (15), prepared from trimethylsilyl-lithium and copper(I) cyanide, reacts with similar substrates, in the same way, even though hexamethylphosphoric triamide (HMPA) is present in the reaction medium.

A model for the cyanide form of oxidized cytochrome oxidase: an iron(III)/copper(II) porphyrin complex displaying ferromagnetic coupling

Abstract: Preparation et proprietes (susceptibilite magnetique, spectres RPE, Mossbauer) d'un compose modele pour l'enzyme citee dans le titre. Etude comparative avec les cytochromes oxydases bovines et bacteriennes

The cyanide content of laetrile preparations, apricot, peach and apple seeds.

Abstract: Laetrile preparations obtained from a cyanide intoxicated patient were analyzed for their cyanide content by a microdiffusion colorimetric procedure. Cyanide was also determined in apricot, peach and apple seeds. The results were compared to those reported in the literature for cyanogenic glycoside containing seeds.

Cyanide removal from aqueous streams

Abstract: The cyanide content of waste waters containing the same is removed by treatment with sulfur dioxide or an alkali or alkaline earth metal sulfite or bisulfite in the presence of excess oxygen and a metal catalyst which is perferably copper.

Acetate synthesis from 2 CO2 in acetogenic bacteria: is carbon monoxide an intermediate?

Abstract: Cultures of Acetobacterium woodii and Clostridium thermoaceticum growing on fructose or glucose, respectively, were found to produce small, but significant amounts of carbon monoxide. In the gas phase of the cultures up to 53 ppm CO were determined. The carbon monoxide production was completely inhibited by 1 mM cyanide. Cultures and cell suspensions of both acetogens incorporated 14CO specifically into the carboxyl group of acetate. This CO fixation into C1 of acetate was unaffected by cyanide (1 mM). The findings are taken to indicate that CO (in a bound form) is the physiological precursor of the C1 of acetate in acetate synthesis from CO2. The cyanide inhibition experiments support the hypothesis that the cyanide-sensitive carbon monoxide dehydrogenase may serve to reduce CO2 to CO rather than to incorporate the carbonyl into C1 of acetate.

Structure and reactivity of multiple forms of cytochrome oxidase as evaluated by X-ray absorption spectroscopy and kinetics of cyanide binding

Abstract: The extended X-ray absorption fine structure (EXAFS) data show differences between the active site structures of different cytochrome oxidase preparations. In the resting (as isolated) state of the Yonetani preparation, the bridging atom between Fe3+a3 and Cu2+a3 is present [Powers, L., Chance, B., Ching, Y., & Angiolillo, P. (1981) Biophys. J. 34, 465], whereas in another preparation (e.g., Hartzell-Beinert), this atom seems to be bound only to Fe3+a3 in a significant fraction of the molecules. Both preparations bind cyanide in a multiphasic fashion, suggesting that the resting cytochrome oxidase is not homogeneous but rather is a mixture of several forms. The proportion of these forms as detected by cyanide binding kinetics differs for different preparations. However, upon reduction and reoxidation (conversion to the "oxygenated" form) the cyanide binding kinetics become monophasic and all preparations of the oxygenated form bind cyanide at the same rate. Thus, a combination of structural and kinetic approaches seems necessary for evaluation of the nature of the active site of cytochrome oxidase in its various forms.

An automated enzymic assay for determining the cyanide content of cassava (Manihot esculenta crantz) and cassava products

Abstract: An automated enzymic method for the analysis of cyanide in cassava and cassava products is described. A total of 300 analyses a day can be handled easily. A wide range of free (nonglycosidic) or bound (cyano-substituted glycosides) cyanides (0.4–40 μg HCN ml−1) can be assayed in the extracted solutions. The upper limit of detection for the bound cyanide can easily be increased by another three-fold by assaying it under partial hydrolysis conditions. The two enzymic methods, manual and automated on Technicon's AutoAnalyzer, agreed well for the free and the bound cyanide in the leaf and the peeled storage root samples.

Inhibition and stimulation of root respiration in pisum and plantago by hydroxamate : its consequences for the assessment of alternative path activity.

Abstract: The contribution of the alternative pathway in root respiration of Pisum sativum L. cv Rondo, Plantago lanceolata L., and Plantago major L. ssp major was determined by titration with salicylhydroxamate (SHAM) in the absence and presence of cyanide. SHAM completely inhibited the cyanide-resistant component of root respiration at 5 to 10 millimolar with an apparent Ki of 600 micromolar. In contrast, SHAM enhanced pea root respiration by 30% at most, at concentrations below 15 millimolar. An unknown oxidase appeared to be responsible for this stimulation. Its maximum activity in the presence of low SHAM concentrations (1-5 millimolar) was 40% of control respiration rate in pea roots, since 25 millimolar SHAM resulted in 10% inhibition. In plantain roots, the maximum activity was found to be 15%. This hydroxamate-activated oxidase was distinct from the cytochrome path by its resistance to antimycin. The results of titrations with cyanide and antimycin indicated that high SHAM concentrations (up to 25 millimolar) block the hydroxamate-activated oxidase, but do not affect the cytochrome path and, therefore, are a reliable tool for estimating the activity of the alternative path in vivo. A considerable fraction of root respiration was mediated by the alternative path in plantain (45%) and pea (15%), in the latter because of the saturation of the cytochrome path.

The absorption of gold cyanide onto activated carbon. II. Application of the kinetic model to multistage absorption circuits

Abstract: A relatively simple rate equation for the kinetics of the absorption of gold from cyanide solutions onto activated carbon was used as the basis in the development of a model for multistage carbon-in-pulp and carbon-in-leach absorption circuits. The model was used in the prediction of both the steady-state and the transient behaviour of the absorption process, and the results were found to be in reasonable agreement with those observed in an extended pilot-plant campaign. A number of practical implications of the model are discussed, and an assessment is made of the economic consequences of the various process options available for the design of a carbon-in-pulp plant.