TY - JOUR

T1 - Copper(ii) complexes with a hybrid phosphinyl-phenanthroline ligand: synthesis, crystal structures and effect of phosphinyl functionalization on the cytotoxicity

AU - Savinykh, P. E.

AU - Golubeva, Yu A.

AU - Smirnova, K. S.

AU - Klyushova, L. S.

AU - Sadykov, E. H.

AU - Artem’ev, A. V.

AU - Lider, E. V.

PY - 2026

Y1 - 2026

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105024207214

UR - https://www.mendeley.com/catalogue/980ddae4-6522-3bb9-a565-057454badeef/

U2 - 10.1039/d5nj03235k

DO - 10.1039/d5nj03235k

M3 - Article

JO - New Journal of Chemistry

JF - New Journal of Chemistry

SN - 1144-0546

ER -