Chemical and physical properties of cyanocobalamin

1. Chemical and physical
properties of cyanocobalamin
Domina Petric, MD

2. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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3. Chemical structures of vitamin B12
Cyanocobalamin
Methylcobalamin
5´-Deoxyadenosylcobalamin
Hydroxocobalamin
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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4. April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
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5. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5

6. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6

7. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7

8. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8

9. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9

10. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10

11. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11

12. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12

13. 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.
April 23, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
13

14. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 23, 2018 14