Chemical and physical properties of cyanocobalamin Domina Petric

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. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 2

Chemical structures of vitamin B 12 Cyanocobalamin Methylcobalamin 5´-Deoxyadenosylcobalamin Hydroxocobalamin January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 3

January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 4

Vitamin B 12 nomenclature • Vitamin B 12 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 B 12 -active corrinoid (also called cobalamin) with a cyano ligand (CN-) at the β position of the cobalt atom. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 5

Vitamin B 12 nomenclature The analogs containing methyl-, 5′-deoxyadenosyl-, hydroxo- (OH) groups at that position are called methylcobalamin, adenosylcobalamin, and hydroxocobalamin (formerly vitamin B 12 b). Those, as well as a form with an unliganded, reduced cobalt center, cob(I)alamin, are found intracellularly. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 6

Vitamin B 12 nomenclature • Other analogs with vitamin B 12 activity include aquacobalamin (formerly vitamin B 12 a) and nitritocobalamin (formerly vitamin B 12 c), which contain aqua- (H 2 O) and nitrite groups. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 7

Physical and chemical properties • Vitamin B 12 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 (CH 3, H 2 O, CN-). • The corrin nucleus consists of four reduced pyrrole nuclei linked by three methylene bridges and one direct bond. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 8

Physical and chemical properties • The triply ionized cobalt atom (Co 3+) 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. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 9

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. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 10

Physical and chemical properties • Vitamin B 12 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. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 11

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 the reduction of the corrin cobalt. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 12

Physical and chemical properties • The vitamin can bind to proteins in the vitamin B 12 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. January 25, 2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 13

Literature • Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. January 25, 2022 14