Copper(II) complexes with tridentate pyrazole-based ligands: synthesis, characterization, DNA cleavage activity and cytotoxicity

Tridentate pyrazole-containing ligands of the Schiff base type, SalPz — HL1, Cl2SalPz — HL2 and I2SalPz — HL3, were used to prepare a series of new Cu(II) complexes (CuSalPz — 1, CuCl2SalPz — 2 and CuI2SalPz — 3). These new complexes have been studied by different analytical techniques (electrospray ionization mass spectrometry (ESI-MS), elemental analysis, FT-IR and EPR). The spectroscopic properties of 1–3 are consistent with the formation of Cu(II) complexes coordinated by monoanionic and tridentate (N,N,O)-chelators, behaving as monomeric species in aqueous solution, as shown by EPR studies. Crystals of 2 and 3, obtained by slow concentration of methanolic solutions of the compounds, were also analyzed by X-ray diffraction analysis. The X-ray structural study has shown that 2 crystallized as a dinuclear compound, [Cu2(μ-Cl)2(Cl2SalPz)2], while the solid state structure determined for 3 is best described by monomeric units of [CuCl(I2SalPz)] displaying short Cu···Cl intermolecular contacts. The in vitro evaluation of 1–3 comprised the study of their DNA-cleaving ability using plasmid DNA and the assessment of their cytotoxic activity against several human cancer cell lines (PC-3 prostate, MCF-7 breast and A2780 and A2780cisR-ovary). The studies with plasmid DNA have shown that 2 and 3 induce extensive DNA cleavage in the presence of different additives. The cytotoxic activity of 2 and 3 is comparable to the one presented by cisplatin, with the exception of the A2780 cell line where cisplatin is more active. It has been found that the introduction of halogen substituents in the phenolate rings of the chelators enhanced the cytotoxicity of the respective Cu(II) complexes.

Graphical abstractNew Cu(II) complexes (1–3) anchored by pyrazolyl-containing (N2O)-chelators (HL1–HL3) were successfully synthesized, and characterized in the solid state and in solution. The synthesized Cu(II) complexes have shown an enhanced nuclease activity in the presence of additives. The measured cytotoxicity and DNA cleavage ability trend may reflect the enhanced stabilization of Cu(I) species.Figure optionsDownload full-size imageDownload as PowerPoint slide