METAL-COMPLEXES OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, LISINOPRIL - SOLUTION STUDIES AND THE CRYSTAL AND MOLECULAR-STRUCTURE OF A DIMERIC COPPER(II)-LISINOPRIL COMPLEX

The binding of the angiotensin-converting enzyme inhibitor lisinopril to zinc(II), copper(II) and nickel(II) has been investigated in soluti on by pH-metric methods and the crystal structure of the dimeric coppe r(II)-lisinopril complex, [Cu-2(HA)(2)(H2O)(2)][ClO4](2) (H(4)A(2+) = fully protonated lisinopril), has been determined. In the case of the metal ions investigated a major species present in neutral or weakly a cidic solution is M(HA)(+), the formation constants of which suggest t hat co-ordination to the metal ions occurs through the amino nitrogen, carboxylate oxygen and the amide oxygen atoms. The crystal structure of the dimeric copper complex shows that each copper is in a distorted square-pyramidal environment in which the basal plane is occupied by carboxylate (Cu-O 1.944 Angstrom) and carbonyl (Cu-O 1.996 Angstrom) o xygens, and an amino group nitrogen (Cu-N 1.989 Angstrom) from one lig and as well as the prolyl carboxylate of another ligand (Cu-O 1.909 An gstrom). An aqua ligand Cu-O (2.355 Angstrom) is axially bonded to eac h copper.