Chemical and physical properties of cyanocobalamin Domina Petric, MD

Essential features of the chemical structure: Cobalt (Co)-centered corrin nucleus. Cobalt α position (below the plane of the corrin ring) may be open or occupied by a side-chain heterocyclic nitrogen, or solvent. Cobalt β position (above the plane of the corrin ring) may be occupied by a hydroxo, aqua, methyl, 5-deoxyadenosyl, CN-, Cl-, Br-, nitro, sulfito or sulfato group. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chemical structures of vitamin B12 Cyanocobalamin Methylcobalamin 5´-Deoxyadenosylcobalamin Hydroxocobalamin November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin B12 nomenclature Vitamin B12 is the generic descriptor for all corrinoids (compounds containing the corrin nucleus) exhibiting the qualitative biological activity of cyanocobalamin. Cyanocobalamin is the trivial designation of the vitamin B12-active corrinoid (also called cobalamin) with a cyano ligand (CN-) at the β position of the cobalt atom. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin B12 nomenclature The analogs containing methyl-, 5′-deoxyadenosyl-, hydroxo- (OH) groups at that position are called methylcobalamin, adenosylcobalamin, and hydroxocobalamin (formerly vitamin B12b). Those, as well as a form with an unliganded, reduced cobalt center, cob(I)alamin, are found intracellularly. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin B12 nomenclature Other analogs with vitamin B12 activity include aquacobalamin (formerly vitamin B12a) and nitritocobalamin (formerly vitamin B12c), which contain aqua- (H2O) and nitrite groups. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Physical and chemical properties Vitamin B12 is an octahedral cobalt complex consisting of a porphyrin-like, cobalt-centered macro-ring (corrin ring or nucleus), a nucleotide, and a second cobalt-bound group (CH3, H2O, CN-). The corrin nucleus consists of four reduced pyrrole nuclei linked by three methylene bridges and one direct bond. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Physical and chemical properties The triply ionized cobalt atom (Co3+) can form up to six coordinate bonds. It is tightly bound to the four pyrrole nitrogen atoms. It can also bond a nucleotide and a small ligand below and above the plane of the ring system. The cobalt atom is removed in vitro only with difficulty, resulting in loss of biological activity. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Physical and chemical properties The corrinoids are red, red-orange or yellow crystalline substances that show intense absorption spectra above 300 nm owing to the π-π transitions of the corrin nucleus. They are soluble in water and are fairly stable to heat, but decompose at temperatures above ∼210°C without melting. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Physical and chemical properties Vitamin B12 reacts with ascorbic acid, resulting in the reduction and subsequent degradation of the former, which releases its cobalt atom as the free ion. Cobalamins with relatively strongly bound ligands (cyano-, methyl- and adenosylcobalamin) are less reactive and more stable in the presence of ascorbic acid. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Physical and chemical properties The cobalamins are unstable to light. Cyanocobalamin undergoes a photoreplacement of the CN- ligand with water. The organocobalamins (methyl- and adenosylcobalamin) undergo photoreduction of the cobalt-carbon bond, resulting in the loss of the ligand and the reduction of the corrin cobalt. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Physical and chemical properties The vitamin can bind to proteins in the vitamin B12 enzymes through an imidazole nitrogen of an histidyl residue on the protein, which serves as the ligand to the lower axial position of the cobalt atom instead of the dimethylbenzimidazole grouping. November 7, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. November 7, 2018