Electron densities of three B12 vitamins

Area of Science:

• Biochemistry
• Crystallography
• Computational Chemistry

Background:

• Vitamin B12 (cobalamin) comprises three natural forms: adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), and cyanocobalamin (CNCbl).
• AdoCbl and MeCbl are essential cofactors in animal life, participating in distinct metabolic pathways.
• Understanding the electronic structure of these vitamins is crucial for elucidating their biological roles.

Purpose of the Study:

• To determine and compare the electron densities of AdoCbl, MeCbl, and CNCbl.
• To investigate the electronic differences and bonding characteristics of the axial ligands in these B12 vitamers.
• To correlate electronic properties with the known biochemical functions of AdoCbl and MeCbl.

Main Methods:

• High-order X-ray diffraction data collection at low temperatures (25 K and 100 K).
• High-level density functional theory (DFT) calculations (BP86/TZVP) for geometry optimization and single-point energy calculations.
• Topological analysis using energy densities, source function, and electron localizability indicator (ELI-D).

Main Results:

• Accurate experimental geometries were obtained for AdoCbl, MeCbl, and CNCbl.
• The source function revealed delocalized interactions between the corrin ring and axial ligands.
• ELI-D analysis indicated unsaturated Co-C(ax) bonding in AdoCbl and MeCbl, but not in CNCbl, suggesting significant pi-backbonding in the latter.
• Inherent electronic differences between AdoCbl and MeCbl were found to be minimal.

Conclusions:

• The electronic structures of AdoCbl and MeCbl are very similar, suggesting that protein-ligand interactions are key to their distinct biochemical reactivities.
• CNCbl exhibits different electronic properties, particularly concerning pi-backbonding, compared to the biologically active forms.
• This study provides a detailed electronic characterization of B12 vitamers, aiding in understanding their function and reactivity.