Probing the nature of the Co(iii) ion in cobalamins: deactivation of the metal towards ligand substitution in 10-nitrosoaquacobalamin, and the kinetics of the ligand substitution reactions of iodocobalamin

Abstract

Aquacobalamin (vitamin B_12a) formally contains a diamagnetic Co(III) ion encapsulated in the small macrocyclic cavity of the corrin ring. Since the ligand substitution reactions, which proceed through a dissociative interchange mechanism, are fast, the usual inertness of d⁶ Co(III) has been modified; this points to the ability of the corrin ring to perturb the properties of the metal ion. This phenomenon is explored further in the present work by replacing the H atom at C10 by an electron withdrawing NO group in 10-nitrosoaquacobalamin. This compound, 10-nitrosoaquacobalamin, is characterised by NMR and UV–vis spectroscopy, and by FAB-MS. The pK_a of coordinated H₂O is determined to be 10.71 ± 0.04 (25 °C, I = 2.2 mol dm⁻³, NaClO₄), ΔH = 120 ± 11 kJ mol⁻¹ and ΔS = 198 ± 38 J K⁻¹ mol⁻¹ (the pK_a of B_12a itself is 8.09). The strongly electron-withdrawing NO group deactivates the metal ion towards ligand substitution, and neither 1.2 mol dm⁻³ pyridine nor 0.7 mol dm⁻³ N₃⁻ result in displacement of coordinated H₂O; either the reactions are very slow (no observable change in 72 hours) or log K has been decreased by at least 1 and 4 orders of magnitude for coordination of these two ligands, respectively. Hence, the electronic structure of the corrin ring can directly influence the axial ligand binding properties of the metal ion. We demonstrate by studying the temperature-dependence of the kinetics of the substitution of I⁻ in iodocobalamin by imidazole, N₃⁻ and S₂O₃²⁻ that, despite the considerable steric barrier of the corrin's peripheral substituents, the nucleophilic participation of the incoming ligand is retained even when changing H₂O to I⁻, which increases the size of the departing ligand.