Estimation of pKa shifts in weak polyacids using a simple molecular model: effects of strong polybases, hydrogen bonding and divalent counterion binding

Abstract

The pKa values of ionizable groups in macromolecules can be significantly different than those of the isolated groups in solution. We have estimated theoretically the changes in the dissociation constant of a weak acid (a) in the vicinity of another ionizable group (b) on the basis of the theoretical approach by Hill (J. Am. Chem. Soc. 78 (1956) 3330) for matching pairs of interacting sites on two large molecules. Three cases are considered for group b: the strong base, the same weak acid as group a with hydrogen bonding between them, and the same weak acid as group a with divalent counterion binding. The pKa shifts are evaluated in each case as a function of the interaction energy between the two ionizable groups and the external salt concentration. The theoretical results provide qualitative explanations for the pKa shifts observed in many experimental systems with weak polyacids (polyampholyte systems like gels and ion exchange membranes, polyelectrolyte multilayers and biological membranes).