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Direct calculation of interconversion barriers in dynamic chromatography and electrophoresis: Isomerization of captopril
Author(s) -
Trapp Oliver
Publication year - 2005
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200410235
Subject(s) - captopril , isomerization , chemistry , chromatography , electrophoresis , computational chemistry , biochemistry , biology , blood pressure , catalysis , endocrinology
Dynamic capillary electrophoresis (DCE) and direct calculation of the rate constants of isomerization has been applied to determine the cis‐trans isomerization barriers of the angiotensin‐converting enzyme inhibitor captopril. The separation of the rotational cis‐trans isomeric drug has been performed in an aqueous 50 m M borate buffer at pH 9.3. Interconversion profiles featuring plateau formation, peak‐broadening, and peak coalescence were observed. To determine the rate constants of the forward and backward reaction ( k cis→trans and k trans→cis ) of the isomerization process in dynamic capillary electrophoresis, a novel straightforward calculation method using the experimental parameters plateau height, h plateau , peak width at half height w h , the total migration times of the cis‐trans isomers t R and the electroosmotic break‐through time t 0 as well as the peak ratio of the cis‐trans isomers is presented for the first time. From temperature dependent measurements the rate constants k cis→trans and k trans→cis and the kinetic activation parameters Δ G ≠ , Δ H ≠ , and Δ S ≠ of the cis‐trans isomerization of captopril were obtained. From the activation parameters the isomerization barriers of captopril at 37°C under basic conditions were calculated to be Δ G ≠ cis→trans = 90.3 kJ·mol −1 and Δ G ≠ trans→cis = 90.0 kJ·mol −1* .