Direct calculation of interconversion barriers in dynamic chromatography and electrophoresis: Isomerization of captopril.
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 mM 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 DeltaG( not equal), DeltaH( not equal), and DeltaS( not equal) of the cis-trans isomerization of captopril were obtained. From the activation parameters the isomerization barriers of captopril at 37 degrees C under basic conditions were calculated to be DeltaG( not equal) (cis-->trans) = 90.3 kJ.mol(-1)and DeltaG( not equal) (trans-->cis) = 90.0 kJ.mol(-1*).
Trapp
Oliver
O
Stanford University, Department of Chemistry, Roth Way, Stanford, CA 94305, USA. trapp@mpi-muelheim.mpg.de
D002216:Captopril / Q000737:chemistry / Q000302:isolation & purification*; D002845:Chromatography; D003198:Computer Simulation; D019075:Electrophoresis, Capillary; D008962:Models, Theoretical; D013237:Stereoisomerism; D013816:Thermodynamics
D002216:Captopril