Determination of the <b><i>cis‐trans</i></b> isomerization barrier of enalaprilat by dynamic capillary electrophoresis and computer simulation

Trapp, Oliver; Trapp, Gabriele; Schurig, Volker

doi:10.1002/elps.200305746

Cited by 21 publications

(23 citation statements)

References 44 publications

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“…Therefore, it is statistically not very probable to find compounds that, being different, can have exactly the same molecular mass and electrophoretic mobility (not even positional isomers, as repeatedly demonstrated in the CE literature, see e.g. [33]). Finally, in regard to our comment that future simulations on the steady-state distribution of CAs should include mixtures of good and poor CAs, it has been pointed out that this has been already done [34].…”

Section: Note Addedmentioning

confidence: 87%

Mass distribution and focusing properties of carrier ampholytes for isoelectric focusing: I. Novel and unexpected results

et al. 2006

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In an attempt to prepare quasi-isoelectric buffers as BGEs for CE, carrier ampholytes (CAs) (Ampholine, pH 7-9; Servalyt, pH 7-9; Bio-Lyte, pH 8-10 and Pharmalyte, pH 8-10.5) have been subdivided with the Rotofor into 20 fractions, of ca. 0.1 pH unit span, whose composition has been studied by CZE-MS. The results have allowed identifying the number of different molecular mass compounds present in every commercial brand, as well as the number of isoforms (having identical mass, but representing positional isomers) associated with a given M(r) value. Ampholine is composed of 29 species, for a total of 85 different isoforms; Bio-Lyte is made of 43 compounds, for a total of 136 isoforms; Pharmalyte comprises 58 different M(r) chemicals, for a total of 102 isoforms and Servalyt is constituted by 65 species, for a total of 306 compounds (all of these values to be considered as minimum numbers, as detected by the present methodology). Surprisingly, and contrary to theory, a very large proportion (up to 70%) of these species are 'poor carrier ampholytes', in that they are unable to focus and are evenly distributed along the generated pH gradient in the electric field. Paradoxically, the pH gradient is created and sustained by the minority of species (30% for three brands, up to 50% for Pharmalyte) that appear to focus at their pI position into reasonably sharp zones. Even in the narrowest pI fraction, up to 20 different compounds can be detected. It is concluded that very few amines with different useful pK values are utilized for the synthesis and that a new generation of CAs with a more diversified population of amines with proper pK values within the given pH intervals should be sought. Ampholine, the poorest of the commercial brands, appears to be still made with the original synthesis devised by Vesterberg, i.e. by reacting a concoction of oligoamines with alpha,beta-unsaturated acids.

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Section: Note Addedmentioning

confidence: 87%

Mass distribution and focusing properties of carrier ampholytes for isoelectric focusing: I. Novel and unexpected results

et al. 2006

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“…As the cis-trans interconversion occurs within the time scale of partitioning, a plateau formation between the two separated peaks of the isomers can be observed [95]. The first kinetic investigation was done by Trapp et al [96]. It was found that in the investigated temperature range the peak ratio of the isomers is temperature dependent and the peak area of the first eluted isomer decreases with increasing temperature (cf.…”

Section: Drugsmentioning

confidence: 97%

“…Therefore, the elution order of the isomers should be trans before cis according to IUPAC rules [98]. The kinetic parameters were obtained by computer simulation of the experimental electropherograms and are summarized in Table 4 [96].…”

Section: Drugsmentioning

confidence: 99%

Investigation of the stereodynamics of molecules and catalyzed reactions by CE

Trapp

2010

Electrophoresis

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The investigation of the molecular dynamics of stereoisomers and the study of the kinetics of reactions, in particular of catalyzed reactions, is of fundamental interest in chemistry, biochemistry, and medicine. Understanding how to control the transition state of a reaction allows for a directed design of new catalysts and benign processes. The integration of reactions and capillary or microchip-based electrophoretic separations is highly attractive to perform on-column derivatizations or enzymatic on-column digests of peptides and proteins for further characterization. The present review article focuses on the recent advances to study the stereodynamics of molecules and reaction kinetics of catalyzed processes by means of CE. Models and algorithms to evaluate interconversion profiles obtained by electrophoretic separation techniques are discussed with respect to the challenging demands of high separation efficiencies typical for electrophoretic techniques. Models used for evaluation are based on iterative computer simulation algorithms using the theoretical plate model or stochastic model of chromatography, empirical calculation methods, derived from equations used in chemical engineering, namely Damköhler analysis, and direct access with the approximation function and more recently with the unified equation, which can be applied to all kinds of first-order reactions taking place during a chromatographic or a electrophoretic separation. Furthermore, areas of applications are presented and discussed to give a guideline for using dynamic CE and on-column reaction electrophoresis to study kinetics of reactions and dynamic processes.

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“…4. With this approach, Schurig and coworkers [23,24] were able to estimate the rate constants for isomerization of AlaPro, Leu-Pro, and Phe-Pro between 0 and 207C as well as for the isomerization of the enzyme inhibitor enalaprit between 0 and 157C. The reported values of k f (cis ?…”

Section: Chromwinmentioning

confidence: 96%

Advances in CE for kinetic studies

Newman

Collins

2007

Electrophoresis

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CE is a promising technique for the investigation of molecular interactions because it affords evaluation of multiple interaction modes, does not require immobilization of molecules, and has no dead time. In order to perform these investigations, numerous methods have been developed for determining binding constants and other thermodynamic parameters. These methods have been reviewed extensively in recent years. However, methods for determining the rates of reaction are less prolific. Nonetheless, numerous theoretical and experimental advances have been made in recent years to address this discrepancy. Some of these methods employ computer simulations to determine first-order or second-order rate constants numerically, whereas other methods calculate rate constants directly as solutions to analytical equations. It is the object of this review to provide descriptions of these methods in terms of their underlying assumptions, experimental methodology, calculation of rate constants, and inherent limitations.

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Determination of the cis‐trans isomerization barrier of enalaprilat by dynamic capillary electrophoresis and computer simulation

Cited by 21 publications

References 44 publications

Mass distribution and focusing properties of carrier ampholytes for isoelectric focusing: I. Novel and unexpected results

Mass distribution and focusing properties of carrier ampholytes for isoelectric focusing: I. Novel and unexpected results

Investigation of the stereodynamics of molecules and catalyzed reactions by CE

Advances in CE for kinetic studies

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