Thermodynamics of acid-base dissociation of several cathinones and 1‐phenylethylamine, studied by an accurate capillary electrophoresis method free from the Joule heating impact

Capillary electrophoresis is often used to the determination of the acid-base dissociation/deprotonation constant (pKa), and the more advanced thermodynamic quantities describing this process (ΔH°, -TΔS°). Remarkably, it is commonly overlooked that due to insufficient dissipation of Joule heating the accuracy of parameters determined using a standard approach may be questionable. In this work we show an effective method allowing to enhance reliability of these parameters, and to estimate the magnitude of errors. It relies on finding a relationship between electrophoretic mobility and actual temperature, and performing pKa determination with the corrected mobility values. It has been employed to accurately examine the thermodynamics of acid-base dissociation of several amine compounds − known for their strong dependency of pKa on temperature: six cathinones (2-methylmethcathinone, 3‐methylmethcathinone, 4-methylmethcathinone, α‐pyrrolidinovalerophenone, methylenedioxypyrovalerone, and ephedrone); and structurally similar 1‐phenylethylamine. The average pKa error caused by Joule heating noted at 25 °C was relatively small − 0.04-0.05 pH unit, however, a more significant inaccuracy was observed in the enthalpic and, in particular, entropic terms. An alternative correction method has also been proposed, simpler and faster, but not such effective in correcting ΔH°/-TΔS° terms. The corrected thermodynamic data have been interpreted with the aid of theoretical calculations, on a ground of the enthalpy-entropy relationships and the most probable structural effects accounting for them. Finally, we have demonstrated that the thermal dependencies of electrophoretic mobility, modelled during the correction procedure, may be directly used to find optimal temperature providing a maximal separation efficiency.