A modular family of gold(I) complexes containing the thiopurine bases 6‐mercaptopurine (6‐MP) or 6‐thioguanine (6‐TG), phosphine or N‐heterocyclic carbene ligands, and appended chromophores (dansyl or nitrobenzoxadiazole, NBD) has been synthesized to develop multimodal chemotherapeutic and photodynamic agents. Whereas gold–thiopurine complexes have been previously explored for dark cytotoxicity, their photodynamic activity and chromophore‐engineered photoresponse remain unreported. The dansyl derivatives display dual emission arising from intramolecular ligand‐to‐ligand energy transfer, while the NBD conjugate exhibits a single band with enhanced photoresponsiveness. All complexes show good stability and moderate lipophilicity, supporting efficient uptake. Cytotoxicity studies in A549 cells reveal clear trends: 6‐TG increases intrinsic cytotoxicity, whereas 6‐MP provides lower dark toxicity and superior performance upon irradiation. The PPh 3 ligand affords the highest phototoxicity indices, and NBD incorporation delivers the strongest photoenhancement, improving IC 50 values by up to an order of magnitude. Mechanistic analyses demonstrate a unified, redox‐mediated apoptotic pathway involving thioredoxin reductase inhibition, reactive oxygen species overproduction, mitochondrial depolarization, partial DNA intercalation, and S‐phase arrest. The photoresponse exhibits clear chromophore dependence, with the NBD–functionalized complex producing singlet oxygen, while the dansyl‐based derivatives favor enhanced hydrogen peroxide generation. These findings establish chromophore‐functionalized gold–thiopurine complexes as a novel and tunable platform for next‐generation multimodal gold‐based anticancer agents.
Agulló et al. (Sun,) studied this question.