Two unsymmetrical dinucleating naphthyridine-based ligands with di(pyridyl) and phosphino side arms were employed in the synthesis of dicopper(I) chloride cores that activate NaBPh 4 to afford bridging phenyl organocopper complexes. In these compounds, the bridging ligand binds symmetrically, as observed in previously described symmetrical dicopper(I) complexes supported by naphthyridine-based ligands with two di(pyridyl) side arms. Unlike the symmetrical systems, however, these complexes undergo quasireversible electrochemical reductions, and chemical reduction yields a diamagnetic product resulting from the coupling of naphthyridine-based radicals of two complexes. The μ-Ph complexes activate the C−H bonds of terminal alkynes and the electron-poor arene C 6 F 5 H. By DFT calculations, the mechanism of terminal alkyne activation involves H-atom transfer at the cationic dicopper center and is sensitive to subtle changes in copper-ligand interactions as well as the position of the anion.

As shown by IncuCyte Zoom imaging proliferation assays, invasive triple‐negative human breast MDA‐MB‐231 cancer cells treated with sub‐toxic doses (5.0‐20 μM, 72 h) of [GaQ3] (Q = 8‐hydroxyquinolinato) caused profound morphological changes and inhibition of cell migration, which were likely due to terminal cell differentiation or similar phenotypical change. This is the first demonstration of potential use of a metal complex in differentiation anti‐cancer therapy. Additionally, a trace amount of Cu(II) (0.20 μM) added to the medium dramatically increased [GaQ3] cytotoxicity (IC50 ~ 2 μM, 72 h) due to its partial dissociation and the action of the HQ ligand as a Cu(II) ionophore, as shown with electrospray mass spectrometry and fluorescence spectroscopy assays in the medium. Hence, cytotoxicity of [GaQ3] is strongly linked to ligand binding of essential metal ions in the medium, e.g., Cu(II). Appropriate delivery mechanisms of such complexes and their ligands could enable a powerful new triple therapeutic approach for cancer chemotherapy, including cytotoxicity against primary tumour, arrest of metastases, and activation of innate and adaptive immune responses.