Synthesis and structural characterization of a zinc(II) complex of the mycobactericidal drug isoniazid – Toxicity against Artemia salina

A new zinc(II) complex of the mycobactericidal drug isoniazid (complex 1) was synthesized and characterized by XRD, vibrational spectroscopy (IR, Raman) and thermogravimetric analysis. The complex is constituted by two isoniazid (INH) molecules, six hydration water molecules and two perchlorate counter-ions for each metal center (C12H26N6Cl2O16Zn). Zinc(II) adopts a distorted octahedral geometry, where two INH molecules coordinate in a bidentate manner through the hydrazide group (N, O) and the other two isoniazid residues complete the coordination sphere of zinc(II) through their aromatic nitrogen atoms. This coordination pattern gives rise to a 2-D coordination polymer. Complex 1 belongs to the monoclinic system [a = 8.1190(2) Å, b = 17.977(4) Å, c = 9.1051(2) Å and β = 100.87(3)°], space group P21. A biological assay with Artemia salina was also performed. Complex 1 is almost 8.5 times more active than the free ligand. Its toxicity against A. salina correlates well with the cytotoxic activity for some human solid tumors. Therefore, antitumoral properties could be expected from complex 1.

A zinc(II) complex of isoniazid (INH) is formed. Zinc(II) adopts a distorted octahedral geometry, where INH molecules coordinate to metal site by hydrazide group and pyridine ring. This coordination gives rise a (4,4) coordination polymer. This complex is almost 8.5 times more active than free ligand against Artemia salina.Figure optionsDownload as PowerPoint slideHighlights
► Tuberculosis is a serious infectious disease and one drug used in its prophylaxis and treatment is isoniazid (INH).
► Interaction of an antibiotic with metals can modulate the biological activity of the drug.
► INH act as bridges between the Zn(II) giving rise to a 2D coordination polymer with (4,4) topology.
► The complex is water soluble and is almost 8.5 times more active than free isoniazid against Artemia salina.