Synthesis, crystal structure, nuclease and in vitro antitumor activities of a new mononuclear copper(II) complex containing a tripodal N3O ligand

We present here the synthesis, crystal structure, electrochemical behavior, spectroscopic properties (FT-IR, UV–Vis and EPR), nuclease and in vitro antitumor activities against human myeloid leukemia cell line of the mononuclear copper complex [Cu(HPClNOL)(Cl)]Cl · MeOH (1). The reaction of the tetradentate ligand HPClNOL [1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol] and 1 equiv. of [Cu(OH2)6](Cl)2, in methanol, resulted in 1, which crystallizes as blue monoclinic crystals. The complex is pentacoordinated with a distorted square-pyramidal geometry. The activity of complex 1 toward plasmid DNA and THP-1 carcinogenic cells was investigated. Complex 1 promotes the cleavage of supercoiled DNA (pBlueScript KS+ DNA) to nicked circular and linear DNA forms. In addition to the three typical KS+ DNA forms, the cleavage resulted in a fourth band, which was visualized above of the nicked circular form. The results reveal that the cleavage mechanism is radical-independent. Furthermore, complex 1 is able to promote cell death of THP-1 cells by apoptosis, as confirmed by fluorescent microscopy, cell morphology and DNA degradation.

Graphical abstractA new mononuclear copper(II) complex [Cu(HPClNOL)Cl]Cl · MeOH (1) was synthesized and completely characterized (IR, UV–Vis, EPR, electrochemical and X-ray diffraction). Complex 1 has promoted the cleavage of plasmid DNA by a hydrolytic pathway. Biological studies carried out in vitro against human myeloid leukemia cells (TPH-1) have shown that complex 1 is active, inhibiting cell proliferation by apoptosis induction.Figure optionsDownload full-size imageDownload as PowerPoint slide