Tridentate acylhydrazone copper(II) complexes with heterocyclic bases as coligands. Synthesis, spectroscopic studies, crystal structure and cytotoxicity assays

Abstract

Two new penta-coordinated copper(II) hydrazone coordination compounds with 2,2́ bipyridine (I) or 1,10 phenanthroline (II) as coligands are synthesized and characterized in the solid state and in solution by spectroscopic methods (FTIR, Raman, UV–vis, EPR). Single crystal X-ray studies show that they have closely related molecular structures with the copper center in a distorted square pyramidal O2N3 environment. The N-acylhydrazone, 4-hydroxy-NŃ-(E)2-hydroxy-3-methoxybenzylidene]benzohydrazide, H2L, coordinates tridentate through its ONO donor atoms as monoanion (HL-) in the cationic complex (I), [Cu(HL)(bipy)](NO3). During the period that takes the synthesis reaction of compound (II), [Cu(L)(o-phen)] to complete, keto-amine to enol-imine tautomerization of H2L occurs and the hydrazone coordinates tridentate as dianionic ligand (L2-). The fivefold coordination sphere of the complexes is completed with the nitrogen atoms of the respective coligands. Cytotoxicity studies against bone (MG-63, IC50(I) = 5.6 ± 1.0 , IC50(II) = 3.5 ± 0.3), breast (MCF7, IC50(I) = 10.8 ± 1.9, IC50(II) = 4.0 ± 1.3), (MDA-MB-231, IC50(I) = 11.4 ± 0.6, IC50(II) = 5.3 ± 0.2) and lung cancer cells (A549, IC50(I) = 7.7 ± 0.7, IC50(II) = 7.0 ± 0.4) reveals increased effectiveness of both complexes compared with the free ligand, the copper nitrate salt and the reference metallodrug cisplatin (CDDP).