Ligand substitution reactions of aquacobalamin: further evidence for a dissociative interchange mechanism, and factors controlling reaction rates

Abstract

The kinetics of the substitution of H₂O in aquacobalamin (vitamin B_12a) by the anionic ligands I^–, S₂O₃^2–, NO₂^–, SCN^– and N₃^– have been determined as a function of ligand concentration and temperature by stopped-flow spectrophotometry at constant ionic strength (2.20 mol dm^–3) and pH (6–7). The observed pseudo-first-order rate constants saturate to a limiting value, K_sat, at high ligand concentrations which is consistent with the reactions proceeding through a dissociative activation pathway. The value of K_sat depends on the entering ligand and the activation parameters for k_sat, ΔH^‡ and ΔS^‡, are directly correlated [ΔH^‡ varies from 26 ± 1 (l^–) to 83 ± 4 (N₃^–) kJ mol^–1 while ΔS^‡ varies from –92 ± 4 (I) to 94 ± 13 (N₃^–) J K^–1 mol^–1]. This is inconsistent with a limiting dissociative (D) mechanism which requires K_sat, and hence ΔH^‡ and ΔS^‡, to be independent of the identity of the entering ligand. The mechanism is therefore best described as a dissociative interchange (I_d) mechanism. There is a direct correlation between ΔH^‡(and hence ΔS^‡) and the total Mulliken population (as determined by semi-empirical molecular orbital methods) of the donor atom of the entering ligand, but no correlation between these activation parameters and the cone angle subtended by the ligand at the metal atom. This suggests that for anionic ligands, in contrast with neutral N-donor ligands, electronic rather than steric effects are primarily responsible for controlling reaction rates. It has been further concluded that for anionic ligands capable of bonding through two different donor atom types the reaction occurs primarily through the donor atom with the higher electron density.