Probing the nature of the Co(III) ion in cobalamins: The reactions of aquacobalamin (vitamin B12a), aqua-10-chlorocobalamin and aqua-10-bromocobalamin with anionic and neutral ligands

•Synthesis and characterisation of aqua-10-bromocobalamin is described.•Substitution of H by Br at C10 favours the binding of anionic ligands.•This substitution retards displacement of axial H2O by azide and imidazole.•Differences in log K and k values are rationalised using DFT calculations.•This demonstrates the importance of cis effects in Co(III) macrocylic chemistry.

The preparation of aqua-(10-bromo)cobalamin, [H2O-(10-Br)Cbl]+, in which the C-10 H of aquacobalamin is substituted by Br, and its characterisation by spectroscopic and by single crystal XRD is described. Equilibrium constants for substitution of H2O by anionic (SO32−, NO2−, SCN−, N3−) and neutral N-donor (imidazole, 4-N,N-dimethylaminopyridine) ligands in [H2OCbl]+, [H2O-(10-Cl)Cbl]+ and [H2O-(10-Br)Cbl]+ are reported. Rate constants and ΔH‡ and ΔS‡ values for the substitution of H2O in [H2O-(10-Br)Cbl]+ by N3− and imidazole are reported, and are compared with values available for [H2OCbl]+ and [H2O-(10-Cl)Cbl]+. Br at C-10 is resonance donating to the corrin. Substitution of the C-10 H by Cl or Br favours the coordination of anionic ligands, but discriminates against the binding of neutral N-donor ligands. DFT (BP86/TZVP) calculations are used to rationalise these observations. When H is changed to Cl or Br, the metal ion becomes less positive and the corrin nucleus becomes more positive, so favouring the coordination of anionic ligands. The kinetics of the substitution of H2O by N3− and imidazole show that both react more slowly with [H2O-(10-Br)Cbl]+ than with [H2OCbl]+. Although ΔH‡ values are smaller, they do not compensate for significantly more negative values of ΔS‡, indicative of a transition state that occurs earlier along the reaction coordinate. Thus perturbation of the electronic structure of a corrin can markedly affect the chemistry of the axial coordination site of Co(III), providing evidence of the importance of cis effects in the chemistry of Co(III) macrocycles.

Graphical abstractThis cis effect of the electronic structure of the corrin on the chemistry of the axial ligand in vitamin B12a derivatives is demonstrated.Figure optionsDownload full-size imageDownload as PowerPoint slide