Enhancing effectiveness of capillary electrophoresis as an analytical tool in the supramolecular acidity modification.

A strategic modification of acidity (pK values) by the non-covalent host-guest interactions is one of the most promising concepts in current supramolecular chemistry. This work is aimed at enhancing the effectiveness of capillary electrophoresis (CE) in determination of pK shifts caused by such interactions and their thermal dependencies crucial in a deep thermodynamic description. We show how to (i) minimize the systematic errors related to Joule heating, (ii) minimize the influence of a voltage ramp time, (iii) speed up pK shift identification and estimation, (iv) interpret thermal effects related to two overlapped dynamic equilibria, and (v) determine pK shifts by an alternative spectrophotometric method (CE-DAD). The proposed solutions were implemented to examine the supramolecular pK shifts of several coumarin derivatives, caused by a variety of structurally different cyclodextrins. It was revealed that a specific host substitution pattern determines the magnitude of apparent pK shifts. Accordingly, heptakis(2,6-di-O-methyl)-β-cyclodextrin induces the much stronger shifts than both non-methylated-β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin applied at the same concentration. We also show that insofar as the complexation of 4-hydroxycoumarin and its derivative (coumatetralyl) are similarly exothermic, the thermal effects accompanying the deprotonation process are remarkably different for both molecules. The pK shift induced by complexation with calixarene was also for the first time determined by a CE method. These observations throw a new light on the background of acidity modification and confirm the applicability of CE as an analytical tool.