Abstract
A strategic modification of acidity (pKa 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 pKa 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 pKa shift identification and estimation, (iv) interpret thermal effects related to two overlapped dynamic equilibria, and (v) determine pKa shifts by an alternative spectrophotometric method (CE-DAD). The proposed solutions were implemented to examine the supramolecular pKa 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 pKa 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 pKa 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.
Highlights
Acidity, usually expressed by a logarithmic equivalent of acid dissociation constant—pKa, is one of the basic physicochemical properties of the ionizable molecules [1]
We show that minimization of the aforementioned problems is possible via (i) utilization of a proper correction strategy basing on the estimation of an actual temperature inside capillary, (ii) concurrent correction of the ramping effect by a simple recalculation, (iii) utilization of a two-values method (TVM) restricted only to two electrophoretic mobility values needed to detect and estimate pKa shift, (iv) specific data handling/analysis that provides an independent insight into two equilibria, and (v) measurement of absorption spectra instead of mobilities in the case of ionizable hosts
We showed how to enhance the analytical potential of capillary electrophoresis (CE) as a tool for the cost- and time-effective screening/identification and accurate determination of the supramolecular pKa shifts
Summary
Usually expressed by a logarithmic equivalent of acid dissociation constant—pKa, is one of the basic physicochemical properties of the ionizable molecules [1]. It determines their solubility in aqueous environment, lipophilicity and membrane permeability, ability to ionic and hydrophobic interactions, activity and functionality in biological systems (including endo- and exo-genic compounds), and particular behaviors in analytical systems, e.g., retention on column in chromatography or migration time in electrophoresis. The recent studies showed that the supramolecular host-guest interactions involving the macrocyclic hosts, like cyclodextrins (CDs), calixarenes, and cucurbiturils, may induce pKa shifts in both directions and of a diverse magnitude, reaching +1.5 pH unit for CDs, +2.4 for calixarenes, and even above +5 units for cucurbiturils [1, 7, 8]. One of the most promising directions of research in this field is the analysis of novel pKa modification systems and thermodynamic investigations focusing on the basic molecular forces governing pKa shifts, expressed quantitatively by the enthalpic and entropic factors [8,9,10]
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