¹H and ¹³C NMR studies of the complexation of Zn²⁺ to the trans isomer of captopril: (A high blood pressure drug)

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