Synthesis, crystal structure, theoretical calculation and cytotoxic effect of new Pt(ii), Pd(ii) and Cu(ii) complexes with pyridine-pyrazoles derivatives

Abstract

The synthesis, structure and cytotoxic activity of Pt(II), Pd(II) and Cu(II) complexes of the general formula MLCl2 (M = Pt, Pd, Cu) 2–4 and (CuLCl2)25 where L is pyrazole-based chelate ligand 3-methyl-1-(2-pyridinyl)-1H-chromene[4,3-c]pyrazol-4-one 1 are described. The complexes were characterized by elemental analysis, infrared and 1H NMR spectroscopy, as well as electrospray mass spectrometry. Compounds 3 and 5 were also studied using X-ray diffraction. In addition, geometries, partial atomic charges, and lipophilicity, which determines their ability to penetrate through cells membranes, were obtained computationally. Complexes 2–4 exhibit square-planar geometries around the metal(II) centers and adopt cis configuration. Complex 5 is a dimer with distorted tetragonal pyramidal configuration at both Cu(II) centers, which are connected by two μ2-chloro bridges in axial positions. The cytotoxic effect of these complexes was examined on HL-60 and NALM-6 human leukemia cells and melanoma WM-115 cells. The Pt-complex cis-2 exhibited moderate cytotoxic activity against leukemic cells, but relatively high activity toward melanoma cells with cytotoxicity of IC50 = 16.6 μM at a level comparable to that of cisplatin (18.2 μM).