Copper(ii) complexes with a hybrid phosphinyl-phenanthroline ligand: synthesis, crystal structures and effect of phosphinyl functionalization on the cytotoxicity

Abstract

Three new mononuclear copper(II) coordination compounds with 2-(diphenylphosphinyl)-1,10-phenanthroline (L) have been synthesized: [CuLCl₂]·1.2H₂O (1), [Cu(H₂O)LBr₂]·0.14EtOH (2) and [Cu(bipy)(H₂O)L](NO₃)₂·2.8H₂O (3). The complexes have been characterized in the solid state by CHN and thermogravimetric analyses, IR spectroscopy, and powder and single-crystal X-ray diffraction, while conductometry and UV-vis spectroscopy were applied for characterization in solution. In the crystal structures, the ligand L adopts a tridentate coordination mode; the metal centers display distorted square-pyramidal geometries in the case of halide complexes, while an octahedral geometry is observed in the nitrate complex. The cytotoxicity of L and complexes 1–3 was investigated against four tumor cell lines (A549, Hep2, HepG2, and MCF7) and non-tumor lung fibroblasts MRC5. All complexes possess cytotoxic activity in the micromolar concentration range. The modification of 1,10-phenanthroline with a diphenylphosphinyl fragment reduces the cytotoxicity of the complexes by an order of magnitude while providing no selectivity advantage over the reference compound [Cu(phen)Cl₂] in the 2D cell model. Meanwhile, the cytotoxicity of complexes 1 and 3 increases at least twofold in the 3D cell model (Hep2 spheroids). Potential mechanisms of action, including apoptosis induction and ROS generation, have been investigated.