Capillary electrophoresis in mixed aqueous-organic solvents: effect of aprotic dipolar N,N-dimethylformamide and N,N-dimethylacetamide on acidity constants of substituted aromatic acids

The change in the pKa values of substituted benzoic acids in binary mixtures of water with N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA), respectively, was determined up to a concentration of 80% (vol/vol) organic cosolvent. Such solvents are applied as media of the background electrolyte in capillary electrophoresis, with the intention of increasing the analyte solubility and the separation selectivity. The pKa values increase nonlinearly with increasing DMF and DMA concentration, and reach values between 2.5 and 3.7 pK units higher than in water at 80% organic solvent content. This change is discussed based on the concept of the medium effect, taking into account the particular stabilization of the species involved in the protolysis equilibria of the acids: HA, A-, and H+, in the different solvents. The contribution of the medium effect of the individual neutral acid HA on the delta pKa values is determined by solubility measurements. The increase in the delta pKa values, averaged for all five acids investigated, is compared in different mixed aqueous-organic media, consisting of methanol, ethanol, 1-propanol, acetonitrile, DMF, and DMA, respectively. The comparison is based on the third-order polynomial fit of the delta pKa versus organic solvent concentration data. It is found that, in this respect, acetonitrile resembles the lower alcohols, and is dissimilar to the other dipolar, aprotic solvents, DMF and DMA. The similarity of the solvent systems is depicted by cluster analysis.