Multifunctional Heterometallic IrIII−AuI Probes as Promising Anticancer and Antiangiogenic Agents

A new class of emissive cyclometallated Ir^III−Au^I complexes with a bis(diphenylphosphino) methanide bridging ligand was successfully synthesised from the diphosphino complex [Ir(N^C)₂(dppm)]⁺ ( 1 ). The different gold ancillary ligand, a triphenylphosphine ( 2 ), a chloride ( 3 ) or a thiocytosine ( 4 ) did not reveal any significant effect on the photophysical properties, which are mainly due to metal-to-ligand charge-transfer (³MLCT) transitions based on Ir^III. However, the Au^I fragment, along with the ancillary ligand, seemed crucial for the bioactivity in A549 lung carcinoma cells versus endothelial cells. Both cell types display variable sensitivities to the complexes (IC₅₀=0.6–3.5 μM). The apoptotic pathway is activated in all cases, and paraptotic cell death seems to take place at initial stages in A549 cells. Species 2 – 4 showed at least dual lysosomal and mitochondrial biodistribution in A549 cells, with an initial lysosomal localisation and a possible trafficking process between both organelles with time. The bimetallic Ir^III−Au^I complexes disrupted the mitochondrial transmembrane potential in A549 cells and increased reactive oxygen species (ROS) generation and thioredoxin reductase (TrxR) inhibition in comparison with that displayed by the monometallic complex 1 . Angiogenic activity assays performed in endothelial cells revealed the promising antimetastatic potential of 1 , 2 and 4 .     

Tunable Anticancer Activity of Furoylthiourea-Based RuII–Arene Complexes and Their Mechanism of Action

Fourteen new Ru^II–arene (p-cymene/benzene) complexes ( C1 – C14 ) have been synthesized by varying the N-terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure–activity relationships of the Ru–p-cymene and Ru–benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR-32 cancer cells, with C5 (Ru–p-cymene complex containing C₆H₂(CH₃)₃ as N-terminal substituent) and C13 (Ru–benzene complex containing C₆H₄(CF₃) as N-terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim-1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells.     

Facile Preparation of WO3−x Dots with Remarkably Low Toxicity and Uncompromised Activity as Co-reactants for Clinical Diagnosis by Electrochemiluminescence

The exceptional nature of WO_3−x dots has inspired widespread interest, but it is still a significant challenge to synthesize high-quality WO_3−x dots without using unstable reactants, expensive equipment, and complex synthetic processes. Herein, the synthesis of ligand-free WO_3−x dots is reported that are highly dispersible and rich in oxygen vacancies by a simple but straightforward exfoliation of bulk WS₂ and a mild follow-up chemical conversion. Surprisingly, the WO_3−x dots emerged as co-reactants for the electrochemiluminescence (ECL) of Ru(bpy)₃²⁺ with a comparable ECL efficiency to the well-known Ru(bpy)₃²⁺/tripropylamine (TPrA) system. Moreover, compared to TPrA, whose toxicity remains a critical issue of concern, the WO_3−x dots were ca. 300-fold less toxic. The potency of WO_3−x dots was further explored in the detection of circulating tumor cells (CTCs) with the most competitive limit of detection so far.     

The First Anticancer Tris(pyrazolyl)borate Molybdenum(IV) Complexes: Tested in Vitro and in Vivo—A Comparison of O,O-, S,O-, and N,N-Chelate Effects

The synthesis, characterization and biological activity of molybdenum(IV) complexes containing Trofimenko's scorpionato ligand, hydrotris(3-isopropylpyrazolyl)borate (Tp^iPr), in addition to varying biologically active as well as other conventional ligands is described. Ligands employed include (O,O-) (S,O-) (N,N-) donors that have been successfully coordinated to the molybdenum center by means of oxygen-atom transfer (OAT) reactions from the known Mo^VI starting material, Tp^iPrMoO₂Cl. The synthesized complexes were characterized by standard analytical methods and where possible by X-ray diffraction analysis. The aqueous stability of the compounds was studied by means of UV/Vis spectroscopy and the impact of the attached ligand scaffolds on the oxidation potentials (Mo^IV to Mo^V) was studied by cyclic voltammetry. Utilizing polyvinylpyrrolidone (PVP) as a solubilizing agent, adequate aqueous solubility for biological tests was obtained. Anticancer activity tests and preliminary mode of action studies have been performed in vitro and in vivo.