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An incident of hydrogen cyanide poisoning.

Seven cases of hydrogen cyanide gas poisoning which occurred in an industrial building in Hong Kong are presented here. Two of them were more severely injured and required specific antidotal treatment. The other five were mild and responded to supportive treatment alone. All except one patient recovered completely. Cyanide poisoning is relatively uncommon in urbanized area, so high index of suspicion is important for early diagnosis and treatment. We believe that prevention of cyanide poisoning can be achieved by proper storage of chemicals, and by enforcing rescuers to wear special chemical protective clothing to avoid systemic poisoning because of dermal absorption of hydrogen cyanide gas. As there are newer and safer cyanide antidotes available, each emergency department should have a stock of updated products such as hydroxocobalamin.

Adult↗

Disruption of cochlear potentials by chemical asphyxiants. Cyanide and carbon monoxide.

While ischemia, hypoxic hypoxia, and carbon monoxide (CO) have received extensive study designed to characterize mechanisms by which they disrupt cochlear function, little data are available concerning cyanide's potential to disrupt auditory function. In this study, disruption of the compound action potential (CAP) and endocochlear potential (EP) by cyanide and CO was compared in rats treated with potassium cyanide (KCN) (7 mg/kg ip), saline, CO (35 ml/kg ip), and air. Acute KCN administration significantly suppressed CAP and EP transiently. The effect was seen initially on EP with CAP impairment occurring a few minutes later. Acute CO injection also suppressed the CAP significantly, but the effect was far smaller, occurred later in time, and lasted longer than the effect of KCN. The effect of CO on EP was equivocal. There was a good correspondence between blood cyanide levels and impairment of cochlear function; carboxyhemoglobin (HbCO) levels were elevated during the period when cochlear function was impaired, but recovery of cochlear function preceded the return of normal oxyhemoglobin. Both KCN and CO had somewhat preferential effects on high-frequency tones. Repeated cyanide administration caused a persistent CAP threshold elevation despite the rapid recovery of EP and CAP observed following acute KCN administration. The data suggest that acute KCN administration has a prominent disruptive effect at the stria vascularis presumably by disrupting the electron transport chain in this metabolically active structure. The principal target for acute CO ototoxicity in the cochlea is probably not the stria vascularis.

Action Potentials↗

Cyanide determination by an ISFET-based peroxidase biosensor.

Horseradish peroxidase immobilized on the surface of an Ion Sensitive Field Effect Transistor (ISFET) can be used for the determination of cyanide ions in aquatic media. When the enzyme is immobilized in BSA gel, the resulting sensor can determine 10(-5)-10(-3) M cyanide. Enzyme immobilization into a positively charged polymer, poly(4-vinylpyridine-co-styrene) (PVPy), seems to cause an increase in cyanide inhibition effects because of anion accumulation in the polymeric matrix, and the resulting sensor can measure cyanide concentration in the range 10(-7)-10(-5) M. Fifty percent peroxidase inactivation was observed with 80 microM KCN in the case of BSA-entrapped enzyme, and with only 0.6 microM KCN when the enzyme was covered by PVPy film. Because of the reversible nature of peroxidase inhibition with cyanide ions, restoration of the enzyme activity after inhibition can be obtained by sensor rewashing in fresh buffer.

Biosensing Techniques↗

The reaction of cyanide with peroxidatic forms of cytochrome oxidase.

The interaction of peroxidatic derivatives of cytochrome c oxidase with cyanide has been investigated by optical spectroscopy and the stopped-flow method. Two reactions were found in the conversion of peroxy cytochrome oxidase to its cyanide complex. The first reaction is characterized by the loss of the 607 nm band, an increase in absorbance at 655 nm, and a decrease in absorbance at 432 nm resulting from a blue-shift of the Soret band; this reaction occurred with a bimolecular rate constant of about 90 M-1 s-1. The second reaction is observed as an absorbance increase at 585 and 432 nm; the latter was due to a red-shift of the Soret band. This second process proceeded with a rate constant of about 22 M-1 s-1. Both reaction rates are linearly dependent on the concentration of cyanide between 5 and 100 mM. The reappearance of the 655 nm band at the completion of the first reaction suggests that cytochrome a3 becomes transiently high-spin, a finding which implies that cyanide is not initially bound to this heme center. It appears that preparations of oxidized CcO contain small but variable amounts of the peroxy form. The variable content of this form is probably responsible for the different response of oxidized oxidase to low concentrations of cyanide [Berka, V., Vygodina, T., Musatov, A., Nicholls, P., & Konstantinov, A. A. (1993) FEBS Lett. 315, 237-241] and may explain the biphasic reduction of the binuclear center with dithionite [Cooper, C. E., Junemann, S., Ioannidis, N., & Wrigglesworth, J. M. (1993) Biochim. Biophys. Acta 1144, 149-160].

Cyanides↗

Laser photolysis behavior of ferrous horseradish peroxidase with carbon monoxide and cyanide: effects of mutations in the distal heme pocket.

Native horseradish peroxidase and several forms with mutations in the distal heme pocket (His42Leu, His42Arg, and Arg38Leu) have been expressed in Escherichia coli. These enzymes have been purified and analyzed in terms of the room temperature recombination rate of carbon monoxide and cyanide after photolysis of the reduced forms. The recombinant wild-type ferrous form exhibited monophasic recombination of carbon monoxide with an observed bimolecular rate constant at pH 8.5 of 4.4 x 10(3) M-1 s-1 which is essentially the same as the natural glycosylated form. This recombination rate constant increases in the mutants in the order WT < H42R < H42L << R38L. The value for R38L (5 x 10(6) M-1 s-1) is increased by 3 orders of magnitude relative to the wild-type and is similar to that for human hemoglobin [Mims et al. (1983) J. Biol. Chem. 258, 14219-14232]. Cyanide recombination with the wild-type ferrous form at room temperature is biphasic at pH 6.5 but becomes more monophasic at pH 8.5, again similar to the behavior of the natural glycosylated form, although the Fe(2+)-cyano form of the recombinant enzyme appears to be more unstable at high pH. None of the mutant forms were able to bind cyanide in the ferrous state to any significant extent (Kdiss > 250 mM) when cyanide was added at a concentration (10-20 mM) sufficient to almost saturate the wild-type form (Kdiss approximately equal to 1 mM at pH 7). This behavior contrasts with that of the oxidized forms of the mutants where increases in cyanide dissociation constants are smaller ( < 25 times).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗

Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 A resolution.

The 1.9 A X-ray crystal structure of human myeloperoxidase complexed with cyanide (R = 0.175, R(free) = 0.215) indicates that cyanide binds to the heme iron with a bent Fe-C-N angle of approximately 157 degrees, and binding is accompanied by movement of the iron atom by 0.2 A into the porphyrin plane. The bent orientation of the cyanide allows the formation of three hydrogen bonds between its nitrogen atom and the distal histidine as well as two water molecules in the distal cavity. The 1.85 A X-ray crystal structure of an inhibitory complex with thiocyanate (R = 0.178, R(free) = 0.210) indicates replacement of chloride at a proximal helix halide binding site in addition to binding in the distal cavity in an orientation parallel with the heme. The thiocyanate replaces two water molecules in the distal cavity and is hydrogen bonded to Gln 91. The 1.9 A structures of the complexes formed by bromide (R = 0.215, R(free) = 0.270) and thiocyanate (R = 0.198, R(free) = 0.224) with the cyanide complex of myeloperoxidase show how the presence of bound cyanide alters the binding site for bromide in the distal heme cavity, while having little effect on thiocyanate binding. These results support a model for a single common binding site for halides and thiocyanate as substrates or as inhibitors near the delta-meso carbon of the porphyrin ring in myeloperoxidase.

Binding, Competitive↗

Geometries and electronic structures of cyanide adducts of the non-heme iron active site of superoxide reductases: vibrational and ENDOR studies.

We have added cyanide to oxidized 1Fe and 2Fe superoxide reductase (SOR) as a surrogate for the putative ferric-(hydro)peroxo intermediate in the reaction of the enzymes with superoxide and have used vibrational and ENDOR spectroscopies to study the properties of the active site paramagnetic iron center. Addition of cyanide changes the active site iron center in oxidized SOR from rhombic high-spin ferric (S = 5/2) to axial-like low-spin ferric (S = 1/2). Low-temperature resonance Raman and ENDOR data show that the bound cyanide adopts three distinct conformations in Fe(III)-CN SOR. On the basis of 13CN, C15N, and 13C15N isotope shifts of the Fe-CN stretching/Fe-C-N bending modes, resonance Raman studies of 1Fe-SOR indicate one near-linear conformation (Fe-C-N angle approximately 175 degrees) and two distinct bent conformations (Fe-C-N angles <140 degrees). FTIR studies of 1Fe-SOR at ambient temperatures reveals three bound C-N stretching frequencies in the oxidized (ferric) state and one in the reduced (ferrous) state, indicating that the conformational heterogeneity in cyanide binding is a characteristic of the ferric state and is not caused by freezing-in of conformational substates at low temperature. 13C-ENDOR spectra for the 13CN-bound ferric active sites in both 1Fe- and 2Fe-SORs also show three well-resolved Fe-C-N conformations. Analysis of the 13C hyperfine tensors for the three substates of the 2Fe-SOR within a simple heuristic model for the Fe-C bonding gives values for the Fe-C-N angles in the three substates of ca. 123 degrees (C3) and 133 degrees (C2), taking a reference value from vibrational studies of 175 degrees (C1 species). Resonance Raman and ENDOR studies of SOR variants, in which the conserved glutamate and lysine residues in a flexible loop above the substrate binding pocket have been individually replaced by alanine, indicate that the side chains of these two residues are not involved in direct interaction with bound cyanide. The implications of these results for understanding the mechanism of SOR are discussed.

Binding Sites↗

Luminescence lifetime-based sensor for cyanide and related anions.

A new Ru(II) complex is described which serves as a luminescence lifetime-based sensor for fluoride and cyanide anions (KF = 640 000 mol-1, KCN = 430 000 mol-1). This chromophore displays observable changes in its UV-vis and steady-state luminescence spectra upon cyanide binding. Prior to cyanide addition, this complex exhibits a single-exponential lifetime (tau = 377 +/- 20 ns). With increasing cyanide concentrations, the intensity decays are composed of two exponentials: long tau (320-370 ns) and short tau (13-17 ns). The average lifetimes shorten as a function of cyanide concentration since the fractional intensity shifts from an initial dominant long lifetime component to the short lifetime component. This work represents the first example of a direct method for the luminescence lifetime-based sensing of anions.

Anions↗

Diferrous cyanides as models for the Fe-only hydrogenases.

The first systematic study of diferrous dicyano dithiolates is described. Oxidation of [Fe2(S2C2H4)(CN)2(CO)4](2-) in the presence of cyanide and tertiary phosphines and of Fe2(S2C2H4)(CO)4(PMe3)2 in the presence of cyanide affords a series of diferrous cyanide derivatives that bear a stoichiometric, structural, and electronic relationship to the H(ox)(air) state of the Fe-only hydrogenases. With PPh3 as the trapping ligand, we obtained an unsymmetrical isomer of Fe2(S2C2H4)(mu-CO)(CN)2(PPh3)2(CO)2, as confirmed crystallographically. This diferrous cyanide features the semibridging CO-ligand, with Fe-muC bond lengths of 2.15 and 1.85 A. Four isomers of Fe2(S2C2H4)(mu-CO)(CN)2(PMe3)2(CO)2 were observed, the initial product again being unsymmetrical but more stable isomers being symmetrical. DFT calculations confirm that the most stable isomers of Fe2(S2C2H4)(mu-CO)(CN)2(PMe3)2(CO)2 have cyanide trans to mu-CO. Oxidative decarbonylation also afforded the new tetracyanide [Fe2(S2C2H4)(mu-CO)(CN)4(CO)2]2-. Insights into the oxidative decarbonylation mechanism of these syntheses come from the spectroscopic characterization of the tetracarbonyl [Fe2(S2C2H4)(mu-CO)(CN)3(CO)3](-). This species reacts with PEt3 to produce the stable adduct [Fe2(S2C2H4)(mu-CO)(CN)3(CO)2(PEt3)](-).

Cyanides↗

Copper(II) catalysis in cyanide conversion into ethyl carbamate in spirits and relevant reactions.

The role of copper(II) species in the oxidation of inorganic cyanide to cyanate and in the conversion of cyanate or urea into ethyl carbamate was investigated. The oxidation process has been shown to be independent from the dissolved oxygen. Elemental analysis and infrared spectroscopy have shown the formation of a mixed copper carbonate/hydroxide in the process of oxidation of cyanide to cyanate in water/ethanol. The complexation to Cu(II) of cyanate formed upon cyanide oxidation makes the former more susceptible to nucleophilic attack from ethanol, with conversion into ethyl carbamate. Comparatively, urea has a minor role with respect to cyanide in the formation of ethyl carbamate. Therefore, the urea present in some samples of Brazilian sugar cane spirit (cachaça) has been shown to have almost no influence on the ethyl carbamate content of cachaças, which comes essentially from cyanide. Fe(II,III) affords results similar to those found with Cu(II). Some suggestions are presented to avoid ethyl carbamate formation in spirits during distillation.

Alcoholic Beverages↗

Microbial destruction of cyanide wastes in gold mining: process review.

Microbial destruction of cyanide and its related compounds is one of the most important biotechnologies to emerge in the last two decades for treating process and tailings solutions at precious metals mining operations. Hundreds of plant and microbial species (bacteria, fungi and algae) can detoxify cyanide quickly to environmentally acceptable levels and into less harmful by-products. Full-scale bacterial processes have been used effectively for many years in commercial applications in North America. Several species of bacteria can convert cyanide under both aerobic and anaerobic conditions using it as a primary source of nitrogen and carbon. Other organisms are capable of oxidizing the cyanide related compounds of thiocyanate and ammonia under varying conditions of pH, temperature, nutrient levels, oxygen, and metal concentrations. This paper presents an overview of the destruction of cyanide in mining related solutions by microbial processes.

Bacteria↗

Creatine kinase-catalyzed reaction rate in the cyanide-poisoned mouse brain.

Brain creatine kinase (CK)-catalyzed phosphorus flux from phosphocreatine (PC) to ATP was measured in vivo in young adult mice made reversibly hypoxic by injection of cyanide. Phosphorus spectra and saturation transfer measurements of CK-catalyzed flux were acquired using a high-field (8.45 T) nuclear magnetic resonance (NMR) spectrometer. After low cyanide doses (1-3 mg/kg of body weight), there were no measurable changes in brain pH or in concentrations of PC, the nucleoside triphosphates (including ATP), and Pi. The CK-catalyzed phosphorus flux increased about 75% after the low cyanide dose. Higher doses (4-6 mg/kg) produced a transient 30-40% decrease in PC concentration, doubling of Pi, and a 0.2 unit decrease in pH. The CK-catalyzed phosphorus flux decreased 50-80% after the higher cyanide doses. This decrease in phosphorus flux was present long after reactant concentrations returned to precyanide values. It is proposed that the increase in brain CK-catalyzed phosphorus flux with the lower cyanide doses is due to an increase in ADP concentration. The large, prolonged decrease in CK-catalyzed reaction rate in the moderately poisoned brain may be due to loss of activity of the mitochondrial CK isoform.

Adenosine Triphosphate↗

Cyanide determination in biological fluids using a microdiffusion method with a flow system and polarographic detection.

The report describes a method for the automated polarographic determination of cyanide as tetracyanonickelate (II) anion complex in a gas-diffusion flow system. The volatile cyanide, existing in whole blood, plasma and urine samples, was measured after gas-diffusion using 8 x 10-5 mol l-1 hexaaminenickel solution as acceptor. The linear range of calibration, for measurements at the hanging mercury-drop electrode (HMDE), was from 0.1 to 2.0 micrograms cyanide with r = 0.998. The RSD was, respectively, 3.4 and 1.2% (n = 5) for 0.4 microgram cyanide measured with and without the flow-system configuration. Detection limits of 7.4 microgram l-1 were calculated using the flow system and the method was compared with the classical method using Cavet flasks. Parameters that affect the cyanide determination in the proposed method, such as acceptor solution, pH, flow rate and temperature, were investigated.

Cyanides↗

Hydrogen cyanide polymers, comets and the origin of life.

Hydrogen cyanide polymers--heterogeneous solids ranging in colour from yellow to orange to brown to black--could be major components of the dark matter observed on many bodies of the outer solar system including asteroids, moons, planets and, especially, comets. The presence on cometary nuclei of frozen volatiles such as methane, ammonia and water subjected to high energy sources makes them attractive sites for the ready formation and condensed-phase polymerization of hydrogen cyanide. This could account for the dark crust observed on Comet Halley in 1986 by the Vega and Giotto missions. Dust emanating from its nucleus would arise partly from HCN polymers as suggested by the Giotto detection of free hydrogen cyanide, CN radicals, solid particles consisting only of H, C and N, or only of H, C, N, O, and nitrogen-containing organic compounds. Further evidence for cometary HCN polymers could be expected from in situ analysis of the ejected material from Comet Tempel 1 after collision with the impactor probe from the two-stage Deep Impact mission on July 4, 2005. Even more revealing will be actual samples of dust collected from the coma of Comet Wild 2 by the Stardust mission, due to return to Earth in January 2006 for analyses which we have predicted will detect these polymers and related compounds. In situ results have already shown that nitriles and polymers of hydrogen cyanide are probable components of the cometary dust that struck the Cometary and Interstellar Dust Analyzer of the Stardust spacecraft as it approached Comet Wild 2 on January 2, 2004. Preliminary evidence (January 2005) obtained by the Huygens probe of the ongoing Cassini-Huygens mission to Saturn and its satellites indicates the presence of nitrogen-containing organic compounds in the refractory organic cores of the aerosols that give rise to the orange haze high in the atmosphere of Titan, Saturn's largest moon. Our continuing investigations suggest that HCN polymers are basically of two types: ladder structures with conjugated -C=N- bonds and polyamidines readily converted by water to polypeptides. Thermochemolysis GC-MS studies show that cleavage products of the polymer include alpha-amino acids, nitrogen heterocycles such as purines and pyrimidines, and provide evidence for peptide linkages. Hydrogen cyanide polymers are a plausible link between cosmochemistry and the origin of informational macromolecules. Implications for prebiotic chemistry are profound. Following persistent bolide bombardment, primitive Earth may have been covered by water and carbonaceous compounds, particularly HCN polymers which would have supplied essential components for establishing protein/nucleic acid life.

Cosmic Dust↗

AMP-dependence of the cyanide-insensitive pathway in the respiratory chain of Paramecium tetraurelia.

The AMP-dependent stimulation of the cyanide-insensitive respiration of Paramecium mitochondria was investigated. The nucleotides exhibiting a stimulatory effect on the cyanide-insensitive oxidation of pyruvate (+ malate) in a medium supplemented with EDTA or carboxyatractyloside were, in decreasing order of efficiency, AMP, GMP, IMP, UMP and TMP. On the other hand, ADP, ATP and cyclic AMP were ineffective. In the presence of carboxyatractyloside, addition of AMP to Paramecium mitochondria incubated with pyruvate (+malate) led to an increase in membrane potential. In the absence of light, the photoactivable derivative of AMP, 3'-[4-[N-(4-azido-2-nitrophenyl)amino]butyryl]-AMP (NAP4-AMP) added to Paramecium mitochondria opposed the stimulatory effect of AMP on the cyanide-insensitive respiration; the Ki for NAP4-AMP was much lower than the Km for AMP, 0.2 microM compared with 120 microM. The ADP-stimulated respiration was not affected. Photoirradiation of Paramecium mitochondria in the presence of NAP4-AMP resulted in irreversible inhibition of the AMP-stimulated cyanide-insensitive respiration. No effect on the ADP-stimulated respiration was observed. A heatlabile cyanide-insensitive ubiquinol oxidase was extracted from Paramecium mitochondria with the detergent NN-dimethyl-N-(3-laurylamidopropyl)amine oxide. The quinol oxidase activity was slightly stimulated by AMP.

Adenosine Diphosphate↗

Cyanide-binding site of bd-type ubiquinol oxidase from Escherichia coli.

We extended our investigation on the structure of the redox centers of bd-type ubiquinol oxidase from Escherichia coli using cyanide as a monitoring probe. We found that addition of cyanide to the air-oxidized O2-bound enzyme caused appearance of an infrared C-N stretching band at 2161 cm-1 and concomitant disappearance of the 647 nm absorption band of the cytochrome d (Fe2+)-O2 species. Addition of cyanide to the air-oxidized CO-bound enzyme also resulted in disappearance of the 635 nm absorption band and the 1983.4 cm-1 C-O infrared band of the cytochrome d (Fe2+)-CO species. The resulting species had a derivative-shaped electron paramagnetic resonance signal at g = 3.15. Upon partial reduction with sodium dithionite, this species was converted partly to a transient heme d (Fe3+)-C = N species having an electron paramagnetic resonance signal at gz = 2.96 and a C-N infrared band at 2138 cm-1. These observations suggest that the active site of the enzyme has a heme-heme binuclear metal center distinct from that of the heme-copper terminal oxidase and that the treatment of the air-oxidized enzyme with cyanide resulted in a cyanide-bridging species with "heme d(Fe3+)-C = N-heme b595(Fe3+)" structure.

Binding Sites↗

High cassava production and low dietary cyanide exposure in mid-west Nigeria.

OBJECTIVE: To investigate if high cassava production levels indicate high consumption and high dietary cyanide exposure in three villages situated within the area of Nigeria with higher cassava production than predicted by a geographic model for cassava production in Africa. DESIGN: Exploratory assessment of: cassava production and processing by qualitative research methods and quantification of residual cyanogens in products; cassava consumption by food frequency and weighed food records and dietary cyanide exposure by urinary thiocyanate and linamarin. SETTING: Rural communities of Afuze, Ebue and Ofabo in mid-west Nigeria. SUBJECTS: 110 subjects from 42 households in three villages for food frequency interviews; 118 subjects in nine Ofabo households for weighed food records. RESULTS: Cassava cultivation was reported to have increased in the preceding 20 years. It was consumed daily by 37 (88%) households, but its mean contribution to daily energy intake was only 13% The range of residual cyanogens in cassava foods was 0 to 62 mg HCN equivalent/kg dry weight (dw). Ten samples (19%) had levels above the 10 mg HCN equivalent/kg dw FAO/WHO safety limit. Mean urinary thiocyanate and linamarin were 51 and 20 micromol/L, indicating low cyanogen intake and dietary cyanide exposure. CONCLUSION: High cassava production levels did not result in high consumption and high dietary cyanide exposure levels, therefore cassava production levels cannot be used to predict consumption or cyanide exposure levels in the study area. A large part of the production is explained by intensive sales.

Adult↗

Application of advanced oxidation processes for the treatment of cyanide containing effluent.

Batch experiments were carried out for the removal of cyanide in the effluent of plating industry by the application of advanced oxidation processes. Four systems with different modes of oxidation in combination of ultra violet (UV) light with hydrogen peroxide and/or ozone were investigated. Of all the applied systems, UV-light with two oxidants, i.e. O3 (32 mg min(-1)), and H2O2 (1.36 g l(-1)) was found successful in bringing down the amount of cyanide from 157.32 mg l(-1) to 1.0 mg l(-1), which is the limit set by the Ministry of Environment of Korea for cyanide-containing discharges. Other systems, however, could not bring the cyanide abatement to the targeted value even with higher dosage of oxidants and an extended period of reaction time. Regardless of the oxidation modes applied, all the heavy metal ions in the treated effluent were reduced to 90%. Ultra violet light with the combination of two oxidants had the economic preference over the other systems since a relatively lower dosage of UV-light (2484 W-S cm(-2)) was found effective at achieving the targeted level of cyanide removal.

Cyanides↗