Cyanide

The cyanide ion, CN⁻.
From the top:
1. Valence-bond structure
2. Space-filling model
3. Electrostatic potential surface
4. 'Carbon lone pair' HOMO

A cyanide is any chemical compound that contains the cyano group (C≡N), which consists of a carbon atom triple-bonded to a nitrogen atom. ^[1] Inorganic cyanides are generally salts of the anion CN⁻.^[2][3] Of the many kinds of cyanide compounds, some are gases; others are solids or liquids. Those that can release the cyanide ion CN⁻ are highly toxic.^[4]

In IUPAC nomenclature, organic compounds that have a –C≡N functional group are called nitriles. Nitriles, on the contrary, are never inorganic compounds. ^{[5] [6]} An example of a nitrile is CH₃CN, acetonitrile, also known as methyl cyanide. Nitriles usually do not release cyanide ions.

A functional group with a hydroxyl and cyanide bonded to the same carbon is called cyanohydrin, and cyanohydridins are hydrolyzed into hydrogen cyanide and a carbonyl compound (ketone or aldehyde).

Etymology

The word "cyanide" was derived from "ferrocyanide", a cyanide derivative of iron. Iron cyanides were first discovered as components of the intensely colored dye Prussian blue. Kyaneos is Greek for "(dark) blue".^[7]

Occurrence

Cyanides are produced by certain bacteria, fungi, and algae and are found in a number of foods and plants. Cyanides are found, although in small amounts, in certain seeds and stones, e.g. those of apple, mango, peach, and bitter almonds.^[8] In plants, cyanides are usually bound to sugar molecules in the form of cyanogenic glycosides and defend the plant against herbivores. Cassava roots (also called manioc), an important potato-like food grown in tropical countries (and the base from which tapioca is made), also contain cyanogenic glycosides.^[9][10]

The cyanide radical CN· has been identified in interstellar space.^[11]

Hydrogen cyanide is produced by the combustion or pyrolysis of certain materials under oxygen-deficient conditions. For example it can be detected in the exhaust of internal combustion engines and tobacco smoke. Certain plastics, especially those derived from acrylonitrile, release hydrogen cyanide when heated or burnt.^[12]

Coordination chemistry

The cyanide anion is a potent ligand for many transition metals.^[13] The very high affinities of metals for this anion can be attributed to its negative charge, compactness, and ability to engage in π-bonding. Well known complexes include:

• hexacyanides [M(CN)₆]³⁻ (M = Ti, V, Cr, Mn, Fe, Co), which are octahedral in shape;
• the tetracyanides, [M(CN)₄]²⁻ (M = Ni, Pd, Pt), which are square planar in their geometry;
• the dicyanides [M(CN)₂]⁻ (M = Cu, Ag, Au), which are linear in geometry.

The deep blue pigment Prussian blue, used in the making of blueprints, is derived from iron cyanide complexes (hence the name cyanide, from cyan, a shade of blue). Prussian blue can produce hydrogen cyanide when exposed to strong acids.

Certain enzymes, the hydrogenase, contain cyanide ligands attached to iron in their active sites. The biosynthesis of cyanide in the [NiFe]-hydrogenases proceeds from carbamoylphosphate, which converts to cysteinyl thiocyanate, the CN⁻ donor.^[14]

Organic derivatives

Because of the cyanide anion's high nucleophilicity, a cyano group is readily introduced into organic molecules by displacement of a halide group (e.g. the chloride on methyl chloride). Organic cyanides are generally called nitriles. Thus, CH₃CN can be methyl cyanide but more commonly is referred to as acetonitrile. In organic synthesis, cyanide is used as a C-1 synthon. I.e., it can be used to lengthen a carbon chain by one, while retaining the ability to be functionalized.

RX + CN⁻ → RCN + X⁻ (Nucleophilic Substitution) followed by

1. RCN + 2 H₂O → RCOOH + NH₃ (Hydrolysis under reflux with mineral acid catalyst), or
2. RCN + 0.5 LiAlH₄ + (second step) 2 H₂O → RCH₂NH₂ + 0.5 LiAl(OH)₄ (under reflux in dry ether, followed by addition of H₂O)

Applications

Mining

Cyanide is mainly produced for the mining of gold and silver: it helps dissolve these metals and their ores. In the cyanide process, finely ground high-grade ore is mixed with the cyanide (concentration of about two kilogram NaCN per tonne); low-grade ores are stacked into heaps and sprayed with a cyanide solution (concentration of about one kilogram NaCN per ton). The precious metals are complexed by the cyanide anions to form soluble derivatives, e.g. [Au(CN)₂]⁻ and [Ag(CN)₂]⁻.^[15]

2 Au + 4 KCN + ½ O₂ + H₂O → 2 K[Au(CN)₂] + 2 KOH

Silver is less "noble" than gold and often occurs as the sulfide, in which case redox is not invoked (no O₂ is required). Instead, a displacement reaction occurs:

Ag₂S + 4 KCN → 2 K[Ag(CN)₂] + K₂S

The "pregnant liquor" containing these ions is separated from the solids, which are discarded to a tailing pond or spent heap, the recoverable gold having been removed. The metal is recovered from the "pregnant solution" by reduction with zinc dust or by adsorption onto activated carbon. This process can result in environmental and health problems. Aqueous cyanide is hydrolyzed rapidly, especially in sunlight. It can mobilize some heavy metals such as mercury if present. Gold can also be associated with arsenopyrite (FeAsS), which is similar to iron pyrite (fool's gold), wherein half of the sulfur atoms are replaced by arsenic. Gold-containing arsenopyrite ores are similarly reactive toward inorganic cyanide.

Cyanide is also used in electroplating.

Industrial organic chemistry

Some nitriles are produced on a large scale, e.g. adiponitrile is a precursor to nylon. Such compounds are often generated by combining hydrogen cyanide and alkenes, i.e., hydrocyanation: RCH=CH₂ + HCN → RCH(CN)CH₃. Metal catalysts are required for such reactions.

Medical uses

The cyanide compound sodium nitroprusside is occasionally used in emergency medical situations to produce a rapid decrease in blood pressure in humans; it is also used as a vasodilator in vascular research. The cobalt in artificial vitamin B₁₂ contains a cyanide ligand as an artifact of the purification process. During World War I, a copper cyanide compound was briefly used by Japanese physicians for the treatment of tuberculosis and leprosy.^[16]

Fishing

Cyanides are illegally used to capture live fish near coral reefs for the aquarium and seafood markets. The practice is controversial, dangerous, and damaging but is driven by the lucrative western market for tropical fish.

Niche uses

Potassium ferrocyanide is used to achieve a blue color on cast bronze sculptures during the final finishing stage of the sculpture. On its own, it will produce a very dark shade of blue and is often mixed with other chemicals to achieve the desired tint and hue. It is applied using a torch and paint brush while wearing the standard safety equipment used for any patina application: rubber gloves, safety glasses, and a respirator. The actual amount of cyanide in the mixture varies according to the recipes used by each foundry.

Cyanide is also used in jewelry-making and certain kinds of photography.

Cyanides are used as insecticides for fumigating ships. Cyanide salts are used for killing ants, and have in some places been used as rat poison (the less toxic poison arsenic is more common).

Although generally thought to be toxic, cyanide and cyanohydrins have been demonstrated to increase germination in various plant species. ^{[17] [18]}

Chemical tests for cyanide

Prussian blue

Iron(II) sulfate is added to a solution suspected of containing cyanide, such as the filtrate from the sodium fusion test. The resulting mixture is acidified with mineral acid. The formation of Prussian blue is a positive result for cyanide.

para-Benzoquinone in DMSO

A solution of para-benzoquinone in DMSO reacts with inorganic cyanide to form a cyanophenol, which is fluorescent. Illumination with a UV light gives a green/blue glow if the test is positive.^[19]

Copper and an aromatic amine

As used by fumigators to detect hydrogen cyanide, copper(II) salt and an aromatic amine such as benzidine is added to the sample; as an alternative to benzidine an alternative amine di-(4,4-bis-dimethylaminophenyl) methane can be used. A positive test gives a blue color. Copper(I) cyanide is poorly soluble. By sequestering the copper(I) the copper(II) is rendered a stronger oxidant. The copper, in a cyanide facilitated oxidation, converts the amine into a colored compound. The Nernst equation explains this process. Another good example of such chemistry is the way in which the saturated calomel reference electrode (SCE) works. The copper, in a cyanide facilitated oxidation converts the amine into a colored compound.

Pyridine-barbituric acid colorimetry

A sample containing inorganic cyanide is purged with air from a boiling acid solution into a basic absorber solution. The cyanide salt absorbed in the basic solution is buffered at pH 4.5 and then reacted with chlorine to form cyanogen chloride. The cyanogen chloride formed couples pyridine with barbituric acid to form a strongly colored red dye that is proportional to the cyanide concentration. This colorimetric method following distillation is the basis for most regulatory methods (for instance EPA 335.4) used to analyze cyanide in water, wastewater, and contaminated soils. Distillation followed by colorimetric methods, however, have been found to be prone to interferences from thiocyanate, nitrate, thiosulfate, sulfite, and sulfide that can result in both positive and negative bias. It has been recommended by the USEPA (MUR March 12, 2007) that samples containing these compounds be analyzed by Gas-Diffusion Flow Injection Analysis — Amperometry.

Gas diffusion flow injection analysis — amperometry

Instead of distilling, the sample is injected into an acidic stream where the HCN formed is passed under a hydrophobic gas diffusion membrane that selectively allows only HCN to pass through. The HCN that passes through the membrane is absorbed into a basic carrier solution that transports the CN to an amperometric detector that accurately measures cyanide concentration with high sensitivity. Sample pretreatment determined by acid reagents, ligands, or preliminary UV irradiation allow cyanide speciation of free cyanide, available cyanide, and total cyanide respectively. These relative simplicity of these flow injection analysis methods limit the interference experienced by the high heat of distillation and also prove to be cost effective since time consuming distillations are not required.

Toxicity

Many cyanide-containing compounds are highly toxic, but some are not. Nitriles (which do not release cyanide ions) and hexacyanoferrates (ferrocyanide and ferricyanide, where the cyanide is already tightly bound to an iron ion) have low toxicities, while most other cyanides are deadly poisonous. Prussian blue, with an approximate formula Fe₇(CN)₁₈ is the blue of blue prints and is administered orally as an antidote to poisoning by thallium and radioactive caesium-137; the large ferrocyanide anion is an effective getter for heavy monovalent cations. The most dangerous cyanides are hydrogen cyanide (HCN) and salts derived from it, such as potassium cyanide (KCN) and sodium cyanide (NaCN), among others. Also some compounds readily release HCN or the cyanide ion, such as trimethylsilyl cyanide (CH₃)₃SiCN upon contact with water and cyanoacrylates upon pyrolysis.

The cyanide anion is an inhibitor of the enzyme cytochrome c oxidase (also known as aa₃) in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It attaches to the iron within this protein. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted, meaning that the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected.

Antidote

Hydroxycobalamin reacts with cyanide to form cyanocobalamin. Cyanocobalamin can be eliminated by the kidneys. This method has the advantage of avoiding the formation of methemoglobin (see below). This antidote kit is sold under the brand name Cyanokit and was approved by the FDA in 2006. ^[20]

An older cyanide antidote kit included administration of three substances: amyl nitrite pearls (inhalation) and sodium nitrite and sodium thiosulfate (infusion). The goal of the antidote is to generate a large pool of ferric iron to compete with cytochrome a₃ (part of the electron transport chain necessary for cellular respiration/energy production) for cyanide. The nitrites oxidize hemoglobin to methemoglobin which competes with cytochrome oxidase for the cyanide ion. Cyanmethemoglobin is formed and cytochrome oxidase is restored. The major mechanism to remove the cyanide from the body is by enzymatic conversion by the mitochondrial enzyme rhodanese to convert cyanate to thiocyanate, which is a relatively non-toxic molecule that is excreted in the urine. To accelerate the detoxification sodium thiosulfate is administered to provide a sulfur donor for rhodanese to produce thiocyanate.

Sensitivity

Minimum Risk Levels (MRLs) may not protect for delayed health effects or health effects acquired following repeated sublethal exposure, like hypersensitivity, asthma, or bronchitis. MRLs may be revised after sufficient data accumulates (Toxicological Profile for Cyanide, U.S. Department of Health and Human Services, 2006).

Notable cyanide deaths

Cyanides have been used as poison many times throughout history.^[21] The most infamous application was the use of hydrogen cyanide (in Zyklon B pellets) by the Nazi regime in Germany for mass murder in some gas chambers during the Holocaust. Cyanides have been used (as in the case of Grigori Rasputin) for attempted murder, and for judicial execution in some parts of the United States. Some notable persons who committed suicide by cyanides (either cyanide salt or hydrogen cyanide) are Eva Braun, Wallace Carothers, Odilo Globocnik, Joseph Goebbels, Hermann Göring, Heinrich Himmler, Adolf Hitler (in combination with a gunshot), Günther von Kluge, Erwin Rommel, Alan Turing and the Liberation Tigers of Tamil Eelam. The mass suicide/murder of The People's Temple in Jonestown was done with cyanide poisoning.

External links

• ATSDR medical management guidelines for cyanide poisoning (US)
• HSE recommendations for first aid treatment of cyanide poisoning (UK)
• Hydrogen cyanide and cyanides (CICAD 61)
• IPCS/CEC Evaluation of antidotes for poisoning by cyanides
• National Pollutant Inventory – Cyanide compounds fact sheet
• Eating apple seeds is safe despite the small amount of cyanide
• Toxicological Profile for Cyanide, U.S. Department of Health and Human Services, July 2006

References

Sources

• Institut national de recherche et de sécurité (1997). "Cyanure d'hydrogène et solutions aqueuses". Fiche toxicologique n° 4, Paris:INRS, 5pp. (PDF file, in French)
• Institut national de recherche et de sécurité (1997). "Cyanure de sodium. Cyanure de potassium". Fiche toxicologique n° 111, Paris:INRS, 6pp. (PDF file, in French)