Quantifying Acidity in Heterogeneous Systems: Biphasic pKa Values

• Published in: Analytical chemistry (Washington) Vol. 94; no. 9; pp. 4059 - 4064
• Main Authors: Leesment, Andre, Selberg, Sigrid, Tammiste, Merili, Vu, Anh Hai, Nguyen, Thuong Hoai, Taylor-King, Luke, Leito, Ivo
• Format: Journal Article
• Language: English
• Published: Washington American Chemical Society 08.03.2022
• Subjects: 1-Octanol; Acidity; Catalysis; Catalysts; Chemical properties; Chemistry; Lipid bilayers; Lipids; Lipophilic; Lipophilicity; Measurement methods; NMR; Nuclear magnetic resonance; Octanol
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.1c05510

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 pKa 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 pKa 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 pKa concept. Biphasic pKa values (pKaow 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) pKaow values depend on concentration. Concentration-independent values were obtained by extrapolating the apparent values to zero concentration using a Debye–Hückel model.