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 solution by pH-metric methods and the crystal structure of the dimeric copper(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 acidic solution is M(HA)(+), the formation constants of which suggest that 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) oxygens, and an amino group nitrogen (Cu-N 1.989 Angstrom) from one ligand as well as the prolyl carboxylate of another ligand (Cu-O 1.909 Angstrom). An aqua ligand Cu-O (2.355 Angstrom) is axially bonded to each copper.