Quantifying Acidity in Heterogeneous Systems: Biphasic pK_a Values

Acidities of lipophilic compounds, such as various ligands or catalysts, in systems consisting of an aqueous phase at equilibrium with a water-immiscible phase (lipid bilayers, phase transfer catalysis, sensor membranes, to name just few) are typically approximated by the aqueous pK_a values. Our research shows that such approximations can lead to seriously biased estimations of the acidities as the bulk of solvated H⁺ ions reside in the aqueous phase, while the lipophilic species─both neutral acid and anion─predominantly reside in the organic phase. Therefore, the use of aqueous pK_a in such situations is not justified. In this work, we provide a more accurate description of the acidities of acids in such systems by applying the biphasic pK_a concept. Biphasic pK_a values (pK_a^ow values) of 35 acids of various structures and chemical properties were determined in a 1-octanol:water system. We provide detailed descriptions of the UV-vis and NMR measurement methods. The directly obtained (apparent) pK_a^ow values depend on concentration. Concentration-independent values were obtained by extrapolating the apparent values to zero concentration using a Debye-Hückel model.