DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B₁₂-Cofactors

Abstract

Density functional theory (DFT)-based normal mode calculations have been carried out on models for B 12 -cofactors to assign reported isotope-edited resonance Raman spectra, which isolate vibrations of the organo-Co group. Interpretation is straightforward for alkyl-Co derivatives, which display prominent Co-C stretching vibrational bands. DFT correctly reproduces Co-C distances and frequencies for the methyl and ethyl derivatives. However, spectra are complex for adenosyl derivatives, due to mixing of Co-C stretching with a ribose deformation coordinate and to activation of modes involving Co-C-C bending and Co-adenosyl torsion. Despite this complexity, the computed spectra provide a satisfactory re-assignment of the experimental data. Reported trends in adenosyl-cobalamin spectra upon binding to the methylmalonyl CoA mutase enzyme, as well as on subsequent binding of substrates and inhibitors, provide support for an activation mechanism involving substrate-induced deformation of the adenosyl ligand.

Performance of DFT in modeling electronic and structural properties of cobalamins

“…Although BP86 predicts closer value to the experiment, that is, 505 cm −1 , the overall performance from a statistical point of view is better for B3LYP. Consequently, the latter was used in recent DFT analysis of Co‐alkyl and Co‐adenosyl vibrational modes in B 12 ‐cofactors 55…”

Ultrafast XANES Monitors Femtosecond Sequential Structural Evolution in Photoexcited Coenzyme B12

“…The lower dimethyl­benzimidazole base was replaced with imidazole (Im), while the amide side chains of corrin ring along with the nucleotide loop have been truncated and replaced with hydrogen atoms. Similar simplified structural models of cobalamins have been successfully used in previous vibrational studies. , Because of the incomplete treatment of correlation energy and to take into account approximately the effects of anharmonicity, scaling of frequencies was applied. , To obtain the best agreement with experiment, the DFT-based computed frequencies of Im-[Co­(III)­corrin]-Ado + were uniformly scaled by 0.86. , …”

“…Similar simplified structural models of cobalamins have been successfully used in previous vibrational studies. 49,50 Because of the incomplete treatment of correlation energy and to take into account approximately the effects of anharmonicity, scaling of frequencies was applied. 51,52 To obtain the best agreement with experiment, the DFT-based computed frequencies of Im-[Co(III)corrin]-Ado + were uniformly scaled by 0.86.…”

“…51,52 To obtain the best agreement with experiment, the DFT-based computed frequencies of Im-[Co(III)corrin]-Ado + were uniformly scaled by 0.86. 49,50 The ground-state XANES spectrum was simulated by using the truncated Im-[Co(III)corrin]-Ado + structure and the FDMNES code. 53,54 The molecule was aligned according to the axis system defined in Figure 1 to allow decomposition of axial and equatorial contributions.…”

Measuring and tracking vitamin B12: A review of current methods with a focus on optical spectroscopy

“…Most studies of vitamin B12 using Raman spectroscopy have concentrated on understanding the molecular structure of the vitamin B12 molecule, for example, in identifying the different vibrational modes of cobalamin (118) and its coenzymes (119). This line of research has given considerable insight into the fine details of the molecular structure of vitamin B12, for example, in characterizing and modeling of the different vibrational modes in the cobalamin molecule (111,120,121), and the chemical and conformational changes it undergoes in the body, for example, during its binding process to the coenzymes it helps to metabolize (122)(123)(124).…”