Copper(ii) complexes with benzhydrazone-related ligands: synthesis, structural studies and cytotoxicity assay

Abstract

The dinuclear copper(II) complexes [Cu₂(L^H)₂] (1), [Cu₂(L^3OMe)₂] (2), [Cu₂(L^4OMe)₂] (3) as well as the tetranuclear complex [Cu₄(L^3OMe)₄]·4MeOH·2H₂O (2a·4MeOH·2H₂O), (where L^H = 2-oxybenzaldehyde benzhydrazonato, L^3OMe = 3-methoxy-2-oxybenzaldehyde benzhydrazonato or L^4OMe = 4-methoxy-2-oxybenzaldehyde benzhydrazonato) were synthesized by reacting copper(II) acetate with the corresponding aroylhydrazone. Reactions in the presence of N-donor ligands D (pyridine, 4,4′-bipyridine or 1,10-phenanthroline) afforded complexes with different nuclearities and Cu : L : D ratios. They can be classified as dinuclear, [Cu₂(L^H)₂(py)₂] (1py), [Cu₂(L^3OMe)₂(py)₂]·3H₂O (2py·3H₂O), [Cu₂(L^4OMe)₂(py)₂] (3py), [{Cu(L^H)}₂(bpy)] (1bpy), [{Cu(L^3OMe)}₂(bpy)] (2bpy), and [{Cu(L^4OMe)}₂(bpy)] (3bpy), mononuclear [Cu(L^H)(phen)] (1phen), [Cu(L^3OMe)(phen)] (2phen) and [Cu(L^4OMe)(phen)] (3phen), and polynuclear [{Cu(L^H)}₂(bpy)]_n·2nMeOH (1bpy*·2MeOH) complexes. Conversion of complexes 1py–3py to complexes 1–3 proceeded via solid state reactions. The crystal and molecular structures of 2a·4MeOH·2H₂O, 2py·3H₂O, 3py, 1bpy*·2MeOH, 2bpy, 1phen and 3phen were determined by the single crystal X-ray diffraction method. All complexes were characterized by means of elemental and thermogravimetric analysis, FT-IR spectroscopy and the powder X-ray diffraction method. In vitro cytotoxicity of benzhydrazone-related ligands and their copper(II) complexes against THP-1 and HepG2 cells demonstrated that the complexes are significantly more cytotoxic than the corresponding ligands.