TY - JOUR

T1 - Copper( ii ) complexes based on 2-ferrocenyl-1,10-phenanthroline: structure, redox properties, cytotoxicity and apoptosis

AU - Ermakova, E. A.

AU - Golubeva, Yu. A.

AU - Klyushova, L. S.

AU - Smirnova, K. S.

AU - Savinykh, P. E.

AU - Romashev, N. F.

AU - Gushchin, A. L.

AU - Zaitsev, K. V.

AU - Osik, N. A.

AU - Fedin, M. V.

AU - Zyryanova, E. Yu.

AU - Utepova, I. A.

AU - Lider, E. V.

N1 - Copper( ii ) complexes based on 2-ferrocenyl-1,10-phenanthroline: structure, redox properties, cytotoxicity and apoptosis / E. A. Ermakova, Y. A. Golubeva, L. S. Klyushova, K. S. Smirnova, P. E. Savinykh, N. F. Romashev, A. L. Gushchin, K. V. Zaitsev, N. A. Osik, M. V. Fedin, E. Y. Zyryanova, I. A. Utepova, E. V. Lider // New Journal of Chemistry. - 2025. DOI 10.1039/d5nj03227j

PY - 2025/9/26

Y1 - 2025/9/26

N2 - Two new copper( ii ) coordination compounds, [CuL(NO 3 ) 2 ] (1) and [CuLCl 2 ]·0.7H 2 O (2), were synthesized and demonstrated high cytotoxicity against tumor cell lines, likely inducing cell death via apoptosis. Two new copper( ii ) coordination compounds, [CuL(NO 3 ) 2 ] (1) and [CuLCl 2 ]·0.7H 2 O (2), were synthesized by the reaction of CuX 2 salts (X = NO 3 − or Cl − ) with 2-ferrocenyl-1,10-phenanthroline (L). The complexes were characterized by elemental, thermogravimetric and high-resolution electrospray mass spectrometric analysis; IR and EPR spectroscopy; cyclic voltammetry; and powder and single-crystal X-ray diffraction analysis. The coordination environment of copper( ii ) in complex 1 is 4 + 2 according to single-crystal X-ray diffraction analysis. The stability of the ligand and complexes in different solvent mixtures (water, phosphate-buffered saline, and cell medium DMEM/F12) was studied using UV-vis spectroscopy and conductometry. Complex 1 was shown to dissociate into [CuL(solvent) n ] 2+ in DMSO and ethanol solutions, while complex 2 was partially dissociated. The observed time-dependent changes in UV-vis spectra likely reflected the oxidation of Fe 2+ to Fe 3+ . The cyclic voltammogram (CV) of L and 1 in DMSO revealed reversible oxidation peaks at 0.61 V and 0.64 V, respectively ( vs. Ag/AgCl), assigned to the Fe( ii )/Fe( iii ) couple whereas the CV of the solution of 2 showed two oxidation peaks. In vitro cytotoxic activity was evaluated against three tumor cell lines (A549, Hep2, and HepG2) and non-tumor lung fibroblasts (MRC5) using 2D and 3D cell models. Compared to the ligand L, both complexes exhibited more pronounced dose-dependent cytotoxicity against all tested cell lines, with LC 50 values in the low micromolar concentration range. Despite containing the redox-active ligand L, neither complex induced significant reactive oxygen species (ROS) production after 1-h incubation with Hep2 cells at concentrations of 1.2–10 μM. However, apoptosis was detected in this cell line, suggesting a possible mechanism of action for the complexes. The effect of complexes on the mitochondrial potential of A549 cells was studied using TMRM.

AB - Two new copper( ii ) coordination compounds, [CuL(NO 3 ) 2 ] (1) and [CuLCl 2 ]·0.7H 2 O (2), were synthesized and demonstrated high cytotoxicity against tumor cell lines, likely inducing cell death via apoptosis. Two new copper( ii ) coordination compounds, [CuL(NO 3 ) 2 ] (1) and [CuLCl 2 ]·0.7H 2 O (2), were synthesized by the reaction of CuX 2 salts (X = NO 3 − or Cl − ) with 2-ferrocenyl-1,10-phenanthroline (L). The complexes were characterized by elemental, thermogravimetric and high-resolution electrospray mass spectrometric analysis; IR and EPR spectroscopy; cyclic voltammetry; and powder and single-crystal X-ray diffraction analysis. The coordination environment of copper( ii ) in complex 1 is 4 + 2 according to single-crystal X-ray diffraction analysis. The stability of the ligand and complexes in different solvent mixtures (water, phosphate-buffered saline, and cell medium DMEM/F12) was studied using UV-vis spectroscopy and conductometry. Complex 1 was shown to dissociate into [CuL(solvent) n ] 2+ in DMSO and ethanol solutions, while complex 2 was partially dissociated. The observed time-dependent changes in UV-vis spectra likely reflected the oxidation of Fe 2+ to Fe 3+ . The cyclic voltammogram (CV) of L and 1 in DMSO revealed reversible oxidation peaks at 0.61 V and 0.64 V, respectively ( vs. Ag/AgCl), assigned to the Fe( ii )/Fe( iii ) couple whereas the CV of the solution of 2 showed two oxidation peaks. In vitro cytotoxic activity was evaluated against three tumor cell lines (A549, Hep2, and HepG2) and non-tumor lung fibroblasts (MRC5) using 2D and 3D cell models. Compared to the ligand L, both complexes exhibited more pronounced dose-dependent cytotoxicity against all tested cell lines, with LC 50 values in the low micromolar concentration range. Despite containing the redox-active ligand L, neither complex induced significant reactive oxygen species (ROS) production after 1-h incubation with Hep2 cells at concentrations of 1.2–10 μM. However, apoptosis was detected in this cell line, suggesting a possible mechanism of action for the complexes. The effect of complexes on the mitochondrial potential of A549 cells was studied using TMRM.

UR - https://www.mendeley.com/catalogue/0d2ae6c6-e6a5-3ec9-82a4-d8953882b63d/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105018693098&origin=inward

U2 - 10.1039/d5nj03227j

DO - 10.1039/d5nj03227j

M3 - Article

JO - New Journal of Chemistry

JF - New Journal of Chemistry

SN - 1144-0546

ER -