Ligand substitution reactions of aquocobalamin. Reactions with primary amines

Abstract

Enthalpies and entropies of activation were determined from the temperature variation of the spectrophotometrically determined pH-independent rate constants for the reaction of nine neutral primary amines with aquocobalamin (vitamin B_12a) in aqueous solution (ionic strength, I= 1.00 mol dm^–3). There are compensating changes in ΔH^‡ and ΔS^‡ for this series of ligands, with ΔH^‡ decreasing from ca. 81 to 58 kJ mol^–1 as ΔS^‡ decreases in parallel from ca. 46 to –46 J K^–1 mol^–1. There is, however, no apparent isokinetic relationship for the series. Plots of ΔH^‡ and ΔS^‡ against the ligand pK_a reveal that the ligands fall into two distinct classes; for a given pK_a value, ligands in the first class [NH₃, NH₂(CH₂)₃OH, NH₂Me and NH₂Pr] have significantly larger ΔH^‡ and ΔS^‡ values than those in the second class [NH₂OMe, NH₂OH, NH₂CH₂CO₂Me, NH₂CH₂CH(OH)CH₂OH and NH₂(CH₂)₂OH]. This is ascribed to ligands in the second class interacting by hydrogen bonding with the acetamide side-chains of the corrin ring and so having their amino groups favourably oriented for interactions with the metal ion.