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New half-sandwich iridium(III) compounds [Ir(η⁵-Cp^x)Cl(L1−3)]PF₆ (1–6), combining Cp* or Cp^ph with N,P-coordinated phosphinoalkylamines L1−L3, were tested in different cancer cells (2D and 3D cultures), including MOR/CPR cisplatin-resistant lung carcinoma. Best-performing compound 3 outperformed its Cp^ph analogue 6 and cisplatin in MOR/CPR cells while sparing noncancerous cells. Multiomics profiling shows a non-DNA-targeted mechanism: rapid integrated stress response with ER stress (DDIT3/CHOP) and oxidative stress (HMOX1, ATF3), nucleolar stress, and primary inhibition of ribosome biogenesis and mitochondrial translation. These changes drive translational shutdown, suppression of oxidative phosphorylation with a glycolytic shift, and G1 arrest, alongside endolysosomal remodeling (enhanced vesicular uptake, reduced degradative capacity) that favors intracellular retention. The phenotype is predominantly cytostatic with apoptotic priming. In vivo, 3 suppressed tumor growth and activated apoptosis with low systemic toxicity. Compound 3 thus emerges as a promising prototype Ir(III) metallodrug that disrupts nucleolar, mitochondrial, and lysosomal homeostasis to overcome resistance.

The study reports the synthesis and characterization of five new hexanuclear Gd(III) coordination compounds with the general formula [Gd(H₃bt)(carboxylate)]₆ (carboxylate = 4-formylbenzoate, 4-bromobenzoate, pivalate, 4-(methylthio)benzoate, where the 4-bromobenzoate derivative was isolated in two distinct polymorphic modifications). This work demonstrates that systematic variation of the carboxylate coligand allows tuning of the magnetic properties while preserving the wheel-shaped structural motif. SQUID magnetometry revealed weak antiferromagnetic (AFM) exchange interactions between neighbouring Gd(III) ions, complemented by a benchmark study of BS-DFT functionals carried out in ORCA. Magneto-structural correlations indicate that AFM coupling strengthens with decreasing Gd···Gd distance and with increasing Hammett substituent constant σ of the aromatic carboxylate substituents. The highest magnetocaloric performance was observed for the pivalate-derived complex, with the MCE correlating primarily with the Gd(III) content per formula unit. The complex bearing a thioether group shows potential for surface deposition onto Au substrates and integration into hybrid materials. Finally, the series serves as a structural model for the preparation of isostructural analogues based on highly anisotropic lanthanide ions (Tb(III), Dy(III), Ho(III)), which may behave as single molecule toroics.

The study describes the design and properties of the half-sandwich Ir(III) complex [Ir(η⁵-Cp)Cl(L1)]PF₆ (1). This complex incorporates a metal-activated Schiff base ligand (L1) featuring a DNA-targeting anthracene substituent. The core of the design is the reactive Schiff base linker, hypothesized to facilitate interactions with small intracellular biomolecules. Research revealed that 1 undergoes a specific cleavage pathway of the Schiff base linker upon interaction with NADH and ascorbate, whereas it remains stable in the presence of glutathione. Compared to its analogue lacking the anthracene moiety (2), compound 1 is more cytotoxic, exhibits stronger DNA binding, and induces higher levels of reactive oxygen species (ROS). DFT calculations confirmed that the coordination of ligand L1 to the iridium centre significantly enhances the reactivity of the Schiff base linker compared to the free ligand. This study provides new insights into the fate of coordinated ligands under simulated intracellular conditions and offers a strategy for developing multicomponent, biomolecule-activated metallodrugs.