Reactivity differences between haemoglobins. II. Electrostatic contribution to the free energy and enthalpy of ionization of methaemoglobins

It was concluded in part I that the differences between the free energies, enthalpies, and entropies of ionization of methaem oglobins A, S, and C are the result of different electrostatic interactions between the protein and the reactive site, and that this arises because of the small differences in their amino acid composition. In this paper the electrostatic contribution to the differences in the free energies of ionizations are calculated, using as a basis for calculation Kirkwood’s model for a protein. These calculations show that the observed differences in free energies may be accounted for quantitatively by the different electrostatic interactions between the protein and reactive site for the three methaemoglobins. The linear relation between ΔH° and TΔS°, reported in part I, is also shown to be the consequence of the electrostatic origin of the differences between these quantities. Other abnormal haemoglobins are considered in the light of the conclusions reached in this paper, and predictions are made concerning the thermodynamics of ionizations of their met forms.