Exploring Gallium(III) Complexes as Emerging Therapeutic Candidates for Breast Cancer.

Despite the clinical success of platinum chemotherapeutics, severe side effects and resistance drive the search for alternative metallodrugs. Gallium compounds are promising due to their ability to mimic iron(III) and disrupt essential cellular processes; however, poor aqueous stability and moderate cytotoxicity have limited their development. Herein, we report a new family of heteroscorpionate gallium(III) salts, [Ga(κ3-NNO)2][GaCl4] (Ga1-Ga6). NMR spectroscopy and single-crystal X-ray diffraction confirmed their molecular structures. The complexes exhibit remarkable air and moisture stability, with tunable lipophilicity and solubility governed by ligand electronics. Ga3 and Ga6, bearing dimethylamino substituents, showed nanomolar cytotoxicity across breast cancer cell lines, outperforming classical platinum drugs. The lead compound Ga6 displayed high hydrolytic stability, selective tumor-cell uptake, cytoplasmic localization, and significant tumor growth inhibition in zebrafish xenografts without observable systemic toxicity in mice, underscoring the potential of the heteroscorpionate platform.