Beyond Electrostatic Screening: Effect of Ion Pairing on Acid–Base Equilibria in Complex Electrolyte Solutions

The modulation of acid-base equilibria by salts is fundamental to solution chemistry, yet its molecular origins in multicomponent electrolyte mixtures remain poorly understood. Building on evidence that individual salts induce ion-specific shifts in weak acid p<i>K</i>_a values, we combine experiment and constant pH molecular dynamics to investigate how ion pairing and specific ion effects govern the p<i>K</i>_a of acetic acid in single and mixed sodium salt solutions. Across anions of varying charge density (sulfate, chloride, iodide), we show that cation-anion association (not electrostatic screening alone) controls the observed p<i>K</i>_a shifts. Notably, in mixed sodium chloride-sulfate solutions, the effects on acetic acid p<i>K</i>_a deviate from additivity due to complex ion-ion interactions. We introduce an ion-pairing-augmented Debye-Hückel model that quantitatively captures these behaviors, providing a predictive framework for pH control in multisalt environments. This work establishes a mechanistic basis for interpreting and predicting pH-dependent phenomena in complex, real-world systems relevant to biochemistry and soft matter.