Reactivity differences between haemoglobins. Part VIII. The thermodynamics of the reaction of human methaemoglobins A and C with fluoride, thiocyanate, and cyanide ions. An interpretation of enthalpy changes in terms of hydration

Abstract

The formation constants of the fluoride, thiocyanate, and cyanide complexes of methaemoglobins A and C have been measured as a function of pH and temperature. The variation with pH of the standard free energy of formation of the complexes is similar in form and comparable in magnitude for all the ligands and for both methaemoglobins. The variation with pH of the enthalpy change is similar in form for all ligands and for both methaemoglobins, ΔH° showing a maximum, but the maximum ΔH° occurs at a higher pH for methaemoglobin C than for methaemoglobin A. The magnitude of the variation of ΔH° with pH is dependent on the nature of the ligand. It is least for fluoride, greater for thiocyanate, and greatest for azide and cyanide ions. The variation with pH of the standard free-energy changes is consistent with a dielectric cavity model for the protein, but the enthalpy changes are not. In order to account for the different enthalpy behaviour for each ligand a mechanism involving hydration changes specific to the iron atoms is proposed. This mechanism is based on the known structure of the haemoglobin molecule in the vicinity of the iron atom and the small changes in structure of sperm whale metmyoglobin in the crystalline state that occur upon complex formation with azide ion. A correlation between the variation with pH of ΔH° of complex formation for a ligand and the magnetic susceptibility of the complex formed by the ligand is discussed.