Photoinduction of Ferroptosis and cGAS-STING Activation by a H₂S-Responsive Iridium(III) Complex for Cancer-Specific Therapy

## Introduction Breast cancer remains a leading cause of cancer-related mortality worldwide, Among nonplatinum metallodrugs, The therapeutic relevance of gallium was first demonstrated with gallium­(III) nitrate, the earliest Ga-based compound evaluated clinically as an antineoplastic agent. Despite this progress, the biological performance of Ga­(III) complexes remains highly dependent on ligand architecture. The coordination sphere governs hydrolytic stability, solubility, redox behavior, and cellular uptake, Scorpionate and heteroscorpionate ligands offer a rigid κ Herein, we report the synthesis, structural characterization, and biological evaluation of a series of alkoxide-functionalized heteroscorpionate Ga­(III) complexes ( ## Conclusions This study describes the design, synthesis, and biological evaluation of a new family of alkoxide-functionalized heteroscorpionate Ga­(III) complexes, introducing a structurally defined κ Systematic modulation of ligand substituents enabled controlled variation of lipophilicity, solubility, and aqueous stability, which translated into distinct cytotoxic profiles across multiple breast cancer subtypes. Within this series, The lead compound Collectively, this work expands the coordination chemistry toolbox available for gallium-based drug design and provides a foundation for the continued development of structurally defined Ga­(III) metallodrugs with improved physicochemical control and preclinical potential.