Metal-dependent Structure, Solution Properties, and Redox-Mediated Anticancer Activity of Rhodium(III) and Iridium(III) Half-Sandwich Phenanthroline-Sulfonamide Complexes.
- 1Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308Gdańsk, Poland.
- 2Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233Gdańsk, Poland.
Abstract
A phenanthroline-bearing sulfonamide ligand (L) and its half-sandwich rhodium(III) and iridium(III) complexes, [(η5-Cp*)RhCl(L)]PF6 (1) and [(η5-Cp*)IrCl(L)]PF6 (2), were synthesized to determine how metal coordination and metal identity influence structure, solution properties, and anticancer responses. Single-crystal X-ray diffraction established closely related piano-stool geometries with bidentate N,N-coordination of L, while spectroscopic analyses confirmed the complexes in solution. All compounds were spectroscopically stable for 72 h under the tested conditions. Coordination shifted the lipophilicity of L (log P = 0.78) to hydrophilic values for 1 and 2 (-0.65 and -0.91, respectively). The complexes weakly inhibited carbonic anhydrase II and displayed low-affinity binding to human serum albumin; the CT-DNA UV-vis experiment was inconclusive because of substantial spectral overlap and was not used to assign a DNA-binding mode. L showed submicromolar-to-low-micromolar cytotoxicity across four cancer cell lines and pronounced time-dependent mitochondrial depolarization in NALM-6 cells. Complex 2 retained micromolar potency but showed weak overall cancer/nonmalignant discrimination, whereas 1 showed a marked preference for NALM-6 cells (IC50 = 4.41 μM; HEK-293 IC50 > 100 μM). In NALM-6 cells, 1 produced a pronounced ROS increase at 6 h that preceded prominent γH2AX signaling, caspase-3/7 activation, and apoptosis at 24-48 h, while mitochondrial depolarization remained comparatively limited. This temporal ordering is consistent with a redox-associated cellular response but does not by itself establish ROS causality or exclude mitochondrial involvement. These matched analogs demonstrate that Rh(III) versus Ir(III) coordination can reprogram physicochemical and cellular response profiles within the same ligand scaffold and identify 1 as a candidate for further mechanism-guided optimization.
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BibTeX
@article{zukowska2026metaldependent,
title = {{Metal-dependent Structure, Solution Properties, and Redox-Mediated Anticancer Activity of Rhodium(III) and Iridium(III) Half-Sandwich Phenanthroline-Sulfonamide Complexes.}},
author = {Natalia Żukowska and Mateusz Kowalik and Natalia Maciejewska and Jan Alfuth and Dawid Dębowski and Katarzyna Kazimierczuk and Mariusz Makowski},
journal = {Inorganic chemistry},
year = {2026},
month = oct,
doi = {10.1021/acs.inorgchem.6c04078},
url = {https://europepmc.org/article/MED/42895382},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metal-dependent Structure, Solution Properties, and Redox-Mediated Anticancer Activity of Rhodium(III) and Iridium(III) Half-Sandwich Phenanthroline-Sulfonamide Complexes.
AU - Natalia Żukowska
AU - Mateusz Kowalik
AU - Natalia Maciejewska
AU - Jan Alfuth
AU - Dawid Dębowski
AU - Katarzyna Kazimierczuk
AU - Mariusz Makowski
PY - 2026
DA - 2026/10/01
JO - Inorganic chemistry
DO - 10.1021/acs.inorgchem.6c04078
UR - https://europepmc.org/article/MED/42895382
AB - A phenanthroline-bearing sulfonamide ligand (L) and its half-sandwich rhodium(III) and iridium(III) complexes, [(η5-Cp*)RhCl(L)]PF6 (1) and [(η5-Cp*)IrCl(L)]PF6 (2), were synthesized to determine how metal coordination and metal identity influence structure, solution properties, and anticancer responses. Single-crystal X-ray diffraction established closely related piano-stool geometries with bidentate N,N-coordination of L, while spectroscopic analyses confirmed the complexes in solution. All compounds were spectroscopically stable for 72 h under the tested conditions. Coordination shifted the lipophilicity of L (log P = 0.78) to hydrophilic values for 1 and 2 (-0.65 and -0.91, respectively). The complexes weakly inhibited carbonic anhydrase II and displayed low-affinity binding to human serum albumin; the CT-DNA UV-vis experiment was inconclusive because of substantial spectral overlap and was not used to assign a DNA-binding mode. L showed submicromolar-to-low-micromolar cytotoxicity across four cancer cell lines and pronounced time-dependent mitochondrial depolarization in NALM-6 cells. Complex 2 retained micromolar potency but showed weak overall cancer/nonmalignant discrimination, whereas 1 showed a marked preference for NALM-6 cells (IC50 = 4.41 μM; HEK-293 IC50 > 100 μM). In NALM-6 cells, 1 produced a pronounced ROS increase at 6 h that preceded prominent γH2AX signaling, caspase-3/7 activation, and apoptosis at 24-48 h, while mitochondrial depolarization remained comparatively limited. This temporal ordering is consistent with a redox-associated cellular response but does not by itself establish ROS causality or exclude mitochondrial involvement. These matched analogs demonstrate that Rh(III) versus Ir(III) coordination can reprogram physicochemical and cellular response profiles within the same ligand scaffold and identify 1 as a candidate for further mechanism-guided optimization.
SN - 0020-1669
SN - 1520-510X
ER -