Determination of the cis-trans isomerization barrier of enalaprilat by dynamic capillary electrophoresis and computer simulation.
Dynamic capillary electrophoresis (DCE) and computer simulation of the elution profiles with the stochastic model has been applied to determine the isomerization barriers of the angiotensin converting enzyme inhibitor enalaprilat. The separation of the rotational cis-trans isomeric drug has been performed in an aqueous 20 mM borate buffer at pH 9.3. Interconversion profiles featuring plateau formation and peak broadening were observed. To evaluate the rate constants k(cis-->trans) and k(trans-->cis) of the cis-trans isomerization from the experimental electropherograms obtained by dynamic capillary electrophoresis, elution profiles were analyzed by a simulation with iterative convergence to the experimental data using the ChromWin software which requires the total migration times of the individual isomers t(R), the electroosmotic break-through time t(0), the plateau height h(plateau), the peak widths at half height of the individual isomers w(h), as well as the peak ratio of the isomers as experimental data input. From temperature-dependent measurements between 0 degrees and 15 degrees C the thermodynamic parameters Delta G, Delta H and Delta S, the rate constants k(cis-->trans) and k(trans-->cis) and the kinetic activation parameters Delta G*, Delta H*, and Delta S* of the cis-trans isomerization of enalaprilat were obtained. From the activation parameters the isomerization barriers at 37 degrees C were calculated to be Delta G* (trans-->cis) = 87.2 kJ.mol(-1) and Delta G*(cis-->trans) = 91.9 kJ.mol(-1).
Trapp
Oliver
O
Universität Tübingen, Institut für Organische Chemie, Tübingen, Germany. trapp@stanford.edu
Trapp
Gabriele
G
Schurig
Volker
V
D003198:Computer Simulation; D019075:Electrophoresis, Capillary / Q000379:methods*; D015773:Enalaprilat / Q000302:isolation & purification*; D019277:Entropy; D006358:Hot Temperature; D013237:Stereoisomerism; D013816:Thermodynamics
D015773:Enalaprilat