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

Abstract

A strategic modification of acidity (pK a 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 a 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 a shift identification and estimation, (iv) interpret thermal effects related to two overlapped dynamic equilibria, and (v) determine pK a shifts by an alternative spectrophotometric method (CE-DAD). The proposed solutions were implemented to examine the supramolecular pK a 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 a 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 a 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-017-0305-y) contains supplementary material, which is available to authorized users.

The Acid-Base/Deprotonation Equilibrium Can Be Studied with a MicroScale Thermophoresis (MST)

“…To fit the MST data in order to determine p K a a sigmoidal Boltzmann curve was used [ 11 ] to describe the change in ionization degree of the molecule in aqueous solutions as a function of pH: where A is the MST response (‰) standing for the non-ionized state asymptote, B is the MST response (‰) standing for the totally ionized state asymptote, x 0 is the inflection point standing for the p K a (50% ionization), and dx is a constant of 0.434 determining the pH range in which the ionization degree increases. This model worked well at finding p K a values based on the electrophoretic data obtained by us in the past [ 12 , 13 ].…”

Derivatization‐free determination of aminoglycosides by CZE–UV in pharmaceutical formulations

“…Capillary temperature can affect the separation efficiency, migration times, detector response, viscosity and, for some molecules, the degree of ionization (p K a changes with temperature) [67,68]. The temperature was evaluated in the range from 25 to 31°C.…”