222
M. J. Toda et al.
2 Electronic and Structural Properties of Cobalamins
As has been briefly outlined in the Introduction, cobalamins typically exist as lowspin octahedral Co(III) complexes with d
6 electronic configuration of Co. The splitting of Co d orbitals is more in line with axially perturbed square planar geometry, with local D 4h symmetry. The equatorial corrin ligand resembles the porphyrin
macrocycle, while the upper and lower positions can be occupied by a variety of
different ligands. Although cobalamins tend to exist in the Co(III) form, other coordination environments are important to consider. These other low oxidation states
include the Co(II) and Co(I) species, which have roles in the context of enzymatic
catalysis and in various photochemical reactions. The Co(II) form, where paramagnetic Co center has d
7 electronic configuration, is produced by one-electron
reduction of Co(III)-based cobalamins and is a five-coordinate species. It can be also
generated upon homolytic cleavage of the Co–C bond, thus forming cob(II)alamin.
Cob(II)alamin is a common intermediate formed in enzymatic reactions catalyzed
by coenzyme B 12 (aka AdoCbl). In all (AdoCbl)-dependent enzymes, the presence
of Co(II) can be detected via electron paramagnetic resonance (EPR) spectroscopy.
Alternatively, Co(II)-based species can also be generated photochemically when
the Co–C bond is cleaved with light. Regardless of environment, solution versus
enzyme, homolytic cleavage of the Co–C bond will lead to a radical pair (RP) formation. One-electron reduction of a Co(II)-based cobalamin leads to a low-spin Co(I)
compound, which has complex electronic structure involving mixture of Co(d
8 ) and
Co(d
7 )/corrin(π
∗ )
1 configurations. The four-coordinate Co(I) form is known as the
super-reduced form of vitamin B 12 and has also been deemed a super-nucleophile
due to its high reactivity. Heterolytic cleavage of the Co–C bond in methylcobalamin
(MeCbl)-dependent enzymes leads to a Co(I) species. The resulting cob(I)alamin
plays key mechanistic roles in B 12 -dependent methyltransferases such as methionine synthase (MetH).
It is worthy to further discuss the importance of the axial base, namely DBI.
Co(III)-based cobalamins can either exist in the base-on or base-off forms. In solution, the attachment of the axial base can be modulated by pH. So, in highly acidic
environments such as pH 2, the axial base will be detached when the DBI is protonated. The Co will remain Co(III) by becoming weakly coordinated to a water
molecule, thus adopting the base-off form. Alternatively, the lower ligand may be
water or can be a histidine (His) residue in certain enzymatic environments. In cases
where the axial base becomes detached in an enzyme, a His residue will coordinate
to the Co. This is known as the base-off/His-on form, and the Co will coordinate
to the nitrogen of the histidine. In the base-on form, whether in solution or in an
enzyme, the Co will coordinate to the nitrogen of the benzimidazole ring.
M. J. Toda et al.
2 Electronic and Structural Properties of Cobalamins
As has been briefly outlined in the Introduction, cobalamins typically exist as lowspin octahedral Co(III) complexes with d
6 electronic configuration of Co. The splitting of Co d orbitals is more in line with axially perturbed square planar geometry, with local D 4h symmetry. The equatorial corrin ligand resembles the porphyrin
macrocycle, while the upper and lower positions can be occupied by a variety of
different ligands. Although cobalamins tend to exist in the Co(III) form, other coordination environments are important to consider. These other low oxidation states
include the Co(II) and Co(I) species, which have roles in the context of enzymatic
catalysis and in various photochemical reactions. The Co(II) form, where paramagnetic Co center has d
7 electronic configuration, is produced by one-electron
reduction of Co(III)-based cobalamins and is a five-coordinate species. It can be also
generated upon homolytic cleavage of the Co–C bond, thus forming cob(II)alamin.
Cob(II)alamin is a common intermediate formed in enzymatic reactions catalyzed
by coenzyme B 12 (aka AdoCbl). In all (AdoCbl)-dependent enzymes, the presence
of Co(II) can be detected via electron paramagnetic resonance (EPR) spectroscopy.
Alternatively, Co(II)-based species can also be generated photochemically when
the Co–C bond is cleaved with light. Regardless of environment, solution versus
enzyme, homolytic cleavage of the Co–C bond will lead to a radical pair (RP) formation. One-electron reduction of a Co(II)-based cobalamin leads to a low-spin Co(I)
compound, which has complex electronic structure involving mixture of Co(d
8 ) and
Co(d
7 )/corrin(π
∗ )
1 configurations. The four-coordinate Co(I) form is known as the
super-reduced form of vitamin B 12 and has also been deemed a super-nucleophile
due to its high reactivity. Heterolytic cleavage of the Co–C bond in methylcobalamin
(MeCbl)-dependent enzymes leads to a Co(I) species. The resulting cob(I)alamin
plays key mechanistic roles in B 12 -dependent methyltransferases such as methionine synthase (MetH).
It is worthy to further discuss the importance of the axial base, namely DBI.
Co(III)-based cobalamins can either exist in the base-on or base-off forms. In solution, the attachment of the axial base can be modulated by pH. So, in highly acidic
environments such as pH 2, the axial base will be detached when the DBI is protonated. The Co will remain Co(III) by becoming weakly coordinated to a water
molecule, thus adopting the base-off form. Alternatively, the lower ligand may be
water or can be a histidine (His) residue in certain enzymatic environments. In cases
where the axial base becomes detached in an enzyme, a His residue will coordinate
to the Co. This is known as the base-off/His-on form, and the Co will coordinate
to the nitrogen of the histidine. In the base-on form, whether in solution or in an
enzyme, the Co will coordinate to the nitrogen of the benzimidazole ring.