Quantifying Acidity in Heterogeneous Systems: Biphasic pK_a Values

Abstract

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.