H-1 AND C-13 NMR-STUDIES OF THE COMPLEXATION OF ZN2- (A HIGH BLOOD-PRESSURE DRUG)( TO THE TRANS ISOMER OF CAPTOPRIL )

Complexation of Zn2+ by captopril, 1-[(2S)-3-mercapto-2-methylpropiony l]-L-proline, has been studied by H-1- and C-13-NMR spectroscopy. The equilibrium constants for the trans to cis isomers bound to Zn2+ were measured for captopril by H-1-NMR spectroscopy. It is observed that th e trans isomer of the drug binds more strongly to Zn2+ between pH 5 to 8. The C-13-NMR spectra show broadening of the trans isomer's resonan ces between pH 5 to 8, and less broadening is observed for the cis iso mer's resonances in the same pH range. At higher pH, hydroxyl ions com pete with the ligand, and the resonances become sharper. At lower pH ( below pH 5), the captopril-Zn2+ complex gave precipitates. Mono and bi dentate mixed complexation of captopril to Zn2+ is proposed.