HPLC Profile of Captopril Disulfide That Undergoes Reversible cis-trans Conversion among Three Isomers

Abstract

Peculiarly shaped chromatograms of some compounds that consist of two reversible isomers have been reported. Those of a compound that consists of three reversible isomers are described here. Because disulfide of captopril has two cistrans convertible bonds, it exists in three forms of cis-cis, cis-trans and trans-trans isomers. The disulfide has produced various HPLC-UV profiles under various conditions, such as three split peaks, three peaks with bridging plateaus and one broad peak. The effect of the column temperature and the eluent flow rate on the profile was investigated and explained by interconversion among three isomers. A profile analysis could provide some kinetic constants of this reaction.

Interaction of serum amyloid P component with hexanoyl bis(D-proline) (CPHPC)

“…6), all of which can regenerate the original chromatogram if collected and reapplied onto the column. These observations provide a close parallel to those reported for the antihypertensive drug captopril (Nishikawa et al, 2004). This Cys-l-Pro inhibitor of angiotensin-converting enzyme oxidizes in the circulation, is excreted as a disulfidelinked palindrome analogous to CPHPC and is subject to cis/ trans isomerization of the peptide bond preceding the proline.…”

“…We also report a highresolution analysis of the interaction of N-acetyl-d-proline, a substructure of CPHPC, with SAP in comparison with the l-isomer. These crystallographic investigations are complemented by calorimetric studies of ligand affinity and measurements of the conformational flexibility of CPHPC in solution, providing a number of parallels with earlier investigations of the angiotensin-converting enzyme inhibitor captopril (Nishikawa et al, 2004).…”

Synthesis, Synchrotron X-ray Diffraction, and Kinetic Studies on the Formation of a Novel Thiolatocobalamin of Captopril: Evidence for cis-trans Isomerization in the β-Axial Ligand.

“…The captopril ligand itself exists as cis and trans isomers in solution with respect to the peptide bond involving the proline amide group ( cis- captopril: trans -captopril ∼60:40, 25 °C, pH 7.4, Scheme ). − Captopril also exists as cis and trans isomers in the solid state, and ACE is inhibited by the trans isomer only. ,, To provide further evidence for the cis - trans isomerization of the captopril ligand in CapSCbl, the effect of temperature and pD on the 1 H NMR spectrum of CapSCbl was investigated. However, unlike captopril, , the relative amounts of the two species remained unchanged with pD (pD 3.4, 7.4, and 9.4), and raising the temperature to 75 °C simply resulted in broadening of all resonances.…”

Chromatographic behavior of the biologically active proline derivative captopril on particulate, monolithic and core–shell narrow bore columns

“…captopril, enalapril, etc.). [2][3][4] Specifically, captopril is an antihypertensive drug that belongs to the angiotensin-converting enzyme (ACE) inhibitor group. It has been used to treat arterial hypertension, some types of congestive heart failure, and post-myocardial infarction.…”