Combined Spectroscopic/Computational Studies of Vitamin B₁₂ Precursors: Geometric and Electronic Structures of Cobinamides

Abstract

Vitamin B12 (cyanocobalamin) and its biologically active derivatives, methylcobalamin and adenosylcobalamin, are members of the family of corrinoids, which also includes cobinamides. As biological precursors to cobalamins, cobinamides possess the same structural core, consisting of a low-spin Co3+ ion that is ligated equatorially by the four nitrogens of a highly substituted tetrapyrrole macrocycle (the corrin ring), but differ with respect to the “lower” axial ligation. Specifically, cobinamides possess a water molecule instead of the nucleotide loop that coordinates axially to Co3+cobalamins via its dimethylbenzimidazole (DMB) base. Compared to the cobalamin species, cobinamides have proven much more difficult to study experimentally, thus far eluding characterization by X-ray crystallography. In this study, we have utilized combined quantum mechanics/molecular mechanics (QM/MM) computations to generate complete structural models of a representative set of cobinamide species with varying upper axial ligands. To validate the use of this approach, analogous QM/MM geometry optimizations were carried out on entire models of the cobalamin counterparts, for which high-resolution X-ray structural data are available. The accuracy of the cobinamide structures was assessed further by comparing electronic absorption spectra computed using time-dependent density functional theory to those obtained experimentally. Collectively, the results obtained in this study indicate that the DMB→H2O lower axial ligand switch primarily affects the energies of the Co 3dz2-based molecular orbital (MO) and, to a lesser extent, the other Co 3d-based MOs as well as the corrin π-based highest energy MO. Thus, while the energies of the lowest-energy electronic transition of cobalamins change considerably as a function of the upper axial ligand, they are nearly invariant for the cobinamides.

Vitamin B12 Catalysis: Probing the Structure/Efficacy Relationship

“…Kozłowski et al. proved that, in the case of 1 , a simplified structure of cobyrinate, bereft of peripheral groups, could be used to compute dissociation energies of the axial ligands (Figure ) . We have additionally incorporated c ‐ and d ‐moieties.…”

“…Kozłowski et al provedt hat, in the case of 1, [33] as implified structureo fc obyrinate, bereft of peripheral groups,c ouldb eu sed to compute dissociation energies of the axial ligands ( Figure 4). [33,34] We have additionally incorporated c-a nd d-moieties. For the initial dataset,t he electron densities of catalysts 2, 10, 13, 15, 18, 20 and 22 were assigned.F irstly, the B3LYP/6-31G(d) level of theory was used, which incorporated the solvent effect (acetonitrile), as implemented in the polarisable continuumm odel (PCM).…”

The Nature of the Co-C Bond Cleavage Processes in Methylcob(II)Alamin and Adenosylcob(III)Alamin

“…Consequently, various properties have been studied, including electron densities and reduction potentials determination [69,76,88,91,96], the comparison of DFT and CASSCF electronic structure data of truncated models of methylcobalamin species [70,71,74,81,85], the infl uence of various factors on the Co-C bond forming and cleavage in methyl-and 5-adenosylcobalamin models [68,[72][73][74][75][76]79,80,83,84,89,90,92,94,97,99,100], and excited states, spectroscopy and photo-dissociation analysis of vitamin B 12 species [78,82,86,87,93,95,98]. We used DFT calculations on Me-Cbl models to calculate total energy as a function of Co-C bond distance as the bond is stretched [39].…”

Stereochemical Properties of Multidentate Nitrogen Donor Ligands and Their Copper Complexes by Electronic CD and DFT

“…These B12 derivatives are extraordinary in the sense that they exhibit unusual reactivity in biological systems and that no other vitamins besides B12 contain a metal ion . Some of the related metal complexes have been investigated using UV–Vis, circular dichroism (CD), magnetic CD (MCD), and ultrafast infrared spectroscopic techniques, as well as using theoretical calculations . Some recent related studies focus on the conformational distributions of multidentate nitrogen donor ligands which have emerged as one of the most versatile synthetic ligands and on their ability to direct helicity of the associated metal complexes .…”

“…1 Some of the related metal complexes have been investigated using UV-Vis, circular dichroism (CD), magnetic CD (MCD), [2][3][4] and ultrafast infrared spectroscopic techniques, 5 as well as using theoretical calculations. [6][7][8] Some recent related studies focus on the conformational distributions of multidentate nitrogen donor ligands which have emerged as one of the most versatile synthetic ligands and on their ability to direct helicity of the associated metal complexes. [9][10][11][12] For example, a recent ECD study examined the relationship between the ECD intensity and the conformational geometries adopted by Jacobsen's ligand, which possesses a trans-cyclohexane-1,2-diamine linkage.…”