|Molar mass||1355.38 g/mol|
|Appearance||Dark red solid|
|Melting point||> 300 °C|
|Boiling point||> 300 °C|
|Solubility in water||Soluble|
|MSDS||External MSDS from Fisher Scientific|
|EU classification||Not available|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
Cyanocobalamin is the most common and widely produced of the chemical compounds that have vitamin activity as vitamin B12. Vitamin B12 is the "generic descriptor" name for any of such vitamers of vitamin B12. Because the body can convert cyanocobalamin to any one of the active vitamin B12 compounds, by definition this makes cyanocobalamin itself a form (or vitamer) of B12, albeit a largely artificial one.
Cyanocobalamin usually does not occur in living organisms, but animals can convert commercially produced cyanocobalamin into active (cofactor) forms of the vitamin, such as methylcobalamin. The amount of cyanide liberated in this process is so small that its toxicity is negligible.
Cyanocobalamin is the most famous and widely produced vitamer in the vitamin B12 family (the family of chemicals that function as B12 when put into the body), because cyanocobalamin is the most air-stable of the B12 forms. It is the easiest to crystallize and, therefore, easiest to purify after it is produced by bacterial fermentation, or synthesized in vitro. It can be obtained as dark red crystals or as an amorphous red powder. Cyanocobalamin is very hygroscopic in the anhydrous form, and sparingly soluble in water (1:80). It is stable to autoclaving for short periods at 121 °C. The vitamin B12 coenzymes are very unstable in light.
In animals the cyanide ligand is replaced by other groups (adenosyl, methyl), which are the biologically active forms. The remaining portion of the cyanocobalamin remains unchanged.
The central cobalt atom normally exists in the trivalent state, Co(III). However, when cyanocobalamin is subjected to various reducing conditions, the central cobalt atom can be reduced to Co(II) or even Co(I), which are usually denoted as B12r and B12s respectively.
B12r and B12s can be prepared from cyanocobalamin by controlled potential reduction, or chemical reduction using sodium borohydride in alkaline solution, zinc in acetic acid, or by the action of thiols. Both B12r and B12s are stable indefinitely under oxygen-free conditions. B12r appears orange-brown in solution, while B12s appears bluish-green under natural daylight, and purple under artificial light.
B12s is the most nucleophilic species known to exist in aqueous solution and is often called a "supernucleophile". This property allows the convenient preparation of cobalamin analogs with different substituents, via nucleophilic attack on the halogenated substituent or unsaturated substituent desired.
For example, cyanocobalamin can be converted to its analog cobalamins via reduction to B12s, followed by the addition of the corresponding alkyl halides, acyl halides, alkene or alkyne. steric hindrance is the major limiting factor in the synthesis of the B12 coenzyme analogs. For example, there is no reaction between neopentyl chloride and B12s, while the secondary alkyl halide analogs are too unstable to be isolated. Research suggest that this is due to the strong coordination between benzimidazole and the central cobalt atom, pulling it down into the plane of corrin ring. The trans effect also determines the polarizability of the Co-C bond so formed. However, once the benzimidazole is detached from cobalt by quaternization with methyl iodide, it is replaced by H2O or hydroxyl ions. Various secondary alkyl halides are then readily attacked by the modified B12s to give the corresponding stable cobalamin analogs. The products are usually extracted and purified by phenol-methylene chloride extraction or by column chromatography.
Cobalamin analogs prepared by this method include the naturally occurring coenzymes methylcobalamin and cobamamide, and also other cobalamins which do not occur naturally, such as vinylcobalamin, carboxymethylcobalamin and cyclohexylcobalamin. This reaction is currently being experimented with for use as a catalyst for chemical dehalogenation, organic reagent and photosensitized catalyst system.
Cyanocobalamin is commercially prepared by bacterial fermentation. Fermentation by a variety of microorganisms yields a mixture of methyl-, hydroxo-, and adenosylcobalamin. These compounds are converted to cyanocobalamin by addition of potassium cyanide in the presence of sodium nitrite and heat. Since a number of species of Propionibacterium produce no exotoxins or endotoxins and have been granted GRAS status (generally regarded as safe) by the Food and Drug Administration of the United States, they are currently the preferred bacterial fermentation organisms for vitamin B12 production.
Historically, a form of vitamin B12 called hydroxocobalamin is often produced by bacteria, and was then changed to cyanocobalamin in the process of being purified in activated charcoal columns after being separated from the bacterial cultures. This change was not immediately realized when vitamin B12 was first being extracted for characterization. Cyanide is naturally present in activated charcoal, and hydroxocobalamin, which has great affinity for cyanide, picks it up, and is changed to cyanocobalamin. Cyanocobalamin is the form in most pharmaceutical preparations because adding cyanide stabilizes the molecule.
France accounts for 80% of world production, and more than 10 tonnes/year of this compound is sold; 55% of sales is destined for animal feed, while the remaining 45% is for human consumption.
Cyanocobalamin is usually prescribed for the following reasons: after surgical removal of part or all of the stomach or intestine to ensure there are adequate levels of vitamin B12 in the bloodstream; to treat pernicious anemia; vitamin B12 deficiency due to low intake from food; thyrotoxicosis; hemorrhage; malignancy; liver or kidney disease. Cyanocobalamin injections are often prescribed to gastric bypass patients having had part of their small intestine bypassed, making it difficult for B12 to be absorbed via food or vitamins. Cyanocobamide is also used to perform the Schilling test to check a person's ability to absorb vitamin B12.
End product of cyanide poisoning treatment
In cases of cyanide poisoning the patient is given hydroxocobalamin, which is a precursor to cyanocobalamin. The hydroxocobalamin binds with the cyanide ion and forms cyanocobalamin which can then be secreted by the kidneys. This has been used for many years in France and was approved by the FDA in Dec 2006, marked under the name Cyanokit.
Possible side effects
The oral use of cyanocobalamin may lead to several allergic reactions such as hives; difficult breathing; swelling of the face, lips, tongue, or throat. Less-serious side effects may include headache, nausea, stomach upset, diarrhea, joint pain, itching, or rash.
In the treatment of some forms of anemia (e.g., megaloblastic anemia), the use of cyanocobalamin can lead to severe hypokalemia, sometimes fatal, due to intracellular potassium shift upon anemia resolution (but this same effect should be observed with any B12 vitamer, not just cyanocobalamin). When treated with vitamin B12, patients with Leber's disease may suffer rapid optic atrophy.
Forms of vitamin B12 for injection (such as hydroxocobalamin itself) are commonly available as pharmaceuticals, and are actually the most commonly used injectable forms of vitamin B12 in many countries. Injectable cyanocobalamin remains the most commonly injectable vitamin B12 in the United States.
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- David Dophin. Preparation of the Reduced Forms of Vitamin B12 and of Some Analogs of the Vitamin B12 Coenzyme Containing a Cobalt-Carbon Bond. D.B. McCormick and L.D. Wright, Eds. 1971;Vol. XVIII:34-54.
- , On the Mechanism of catalysis by Vitamin B12, by Jonothan D. Brodie.
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