Pavel Dubský

Enhanced selectivity in CZE multi-chiral selector enantioseparation systems: proposed separation mechanism.

It has been reported many times that the commercial mixtures of chiral selectors (CS), namely highly sulfated β‐CDs (HS‐β‐CDs), provide remarkable enantioselectivity in CZE when compared with single‐isomer CDs, even single‐isomer HS‐β‐CDs. This enhanced enantioselectivity of multi‐CS enantioseparative CZE is discussed in the light of multi‐CS model that we have introduced earlier. It is proposed on a theoretical basis and verified experimentally that the two enantiomers of a chiral analyte under interaction with a mixture of CSs are very likely to differ in their limit mobilities, which is opposite to single‐CS systems where the two limit mobilities are likely to be the same. Thus while the enantioseparation is usually controlled by different distribution constants between the two enantiomers and CS used in single‐CS systems, an additional, electrophoretic, enantioselective mechanism resulting from different limit mobilities may play a significant role in multi‐CS systems. This additional mechanism generally makes the multi‐CS systems more selective than the single‐CS systems. The possible inequality of limit mobilities is also significant for optimization of separation conditions using mixtures of CSs. A practical example supporting our considerations is shown on enantioseparation of lorazepam in the presence of a commercial mixture of HS‐β‐CDs and a single‐isomer HS‐β‐CD, heptakis(6‐O‐sulfo)‐β‐CD.

Model of CE enantioseparation systems with a mixture of chiral selectors: Part I. Theory of migration and interconversion☆

Theory of equilibria, migration and dynamics of interconversion of a chiral analyte in electromigration enantioseparation systems involving a mixture of chiral selectors for the chiral recognition (separation) are proposed. The model assumes that each individual analyte-CS interaction is fast, fully independent on other interactions and the analyte can interact with CS in 1:1 ratio and that the analyte is present in the concentration small enough not to considerably change the concentration of free CSs. Under these presumptions, the system behaves as there was only one chiral selector with a certain overall equilibrium constant, overall mobility of analyte-selector complex (associate) and overall rate constant of interconversion in a chiral environment. We give the mathematical equations of the overall parameters. A special interest is devoted to the dynamics of interconversion. Interconversion in systems with mixture of chiral selectors is governed by two apparent rate constants of interconversion in the same way as in case of singe-selector systems. We propose the experimental design that allows to determine rates of interconversion in both chiral and achiral parts of the enantioseparation system separately. The approach is verified experimentally in the second part of the article.

Twenty years of development of dual and multi-selector models in capillary electrophoresis: a review.

It has been 20 years since Lurie et al. first published their model of electromigration of an analyte under simultaneous interaction with two cyclodextrins as chiral selectors. Since then, the theory of (enantio)separation in dual and complex mixtures of (chiral) selectors is well understood. In spite of this, a trial‐and‐error approach still prevails in analytical practice. Such a situation is likely caused by the fact that the entire theory is spread over numerous papers and the relations between various models are not always clear. The present review condenses the theory for the first time. Available mathematical models and feasible practical approaches are summarized and their advantages and limitations discussed.

Simulation of the effects of complex‐formation equilibria in electrophoresis: III. Simultaneous effects of chiral selector concentration and background electrolyte pH

This paper describes the results of the second‐level testing of the simulation program Simul 5 Complex. We compare the published experimental results with the simulated migration behavior of the enantiomers at different pH and chiral selector concentration values and use the same optimization object function, separation selectivity, as the original papers. Simul 5 Complex proved to be a suitable tool for the prediction of the effective mobilities, separation selectivities, and migration order reversals in these pH‐dependent and CD concentration dependent enantiomer separations. In addition, by performing simulations of four different separations systems (both real and model systems), Simul 5 Complex revealed the existence of unexpected and hitherto unexplained electromigration dispersion effects that were caused by the complexation process itself and could significantly impair the quality of the separations.

Affinity capillary electrophoresis: the theory of electromigration

AbstractWe focus on the state-of-the-art theory of electromigration under single and multiple complexation equilibrium. Only 1:1 complexation stoichiometry is discussed because of its unique status in the field of affinity capillary electrophoresis (ACE). First, we summarize the formulas for the effective mobility in various ACE systems as they appeared since the pioneering days in 1992 up to the most recent theories till 2015. Disturbing phenomena that do not alter the mobility of the analyte directly but cause an unexpected peak broadening have been studied only recently and are also discussed in this paper. Second, we turn our attention to the viscosity effects in ACE. Change in the background electrolyte viscosity is unavoidable in ACE but numerous observations scattered throughout the literature have not been reviewed previously. This leads to an uncritical employment of correction factors that may or may not be appropriate in practice. Finally, we consider the ionic strength effects in ACE, too. Limitations of the current theories are also discussed and the tasks identified where open problems still prevail. Graphical AbstractA weak base (A) undergoes an acidic-basic equilibria (in blue) and migrates with an electrophoretic mobility of μA0

Generalized model of electromigration with 1:1 (analyte:selector) complexation stoichiometry: Part I. Theory

{\mu}_A^0

Generalized model of electromigration with 1:1 (analyte:selector) complexation stoichiometry: part II. Application to dual systems and experimental verification.

. Simultaneously, it interacts with a selector (sel) while the analyte-selector complex migrates with an electrophoretic mobility of μAsel