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Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well‐defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox‐based approaches to cancer therapy. [ABSTRACT FROM AUTHOR]

Synthesis and purification of metal clusters without strong binding agents by wet chemical methods are very attractive for their potential applications in many research areas. However, especially challenging is the separation of uncharged clusters with only a few number of atoms, which renders the usual techniques very difficult to apply. Herein, we report the first efficient separation of Ag2 and Ag3 clusters using the different entropic driving forces when such clusters interact with DNA, into which Ag3 selectively intercalates. After sequential dialysis of the samples and denaturalizing the DNA‐Ag3 complex, pure Ag2 can be found in the dialysate after extensive dialysis. Free Ag3 is recovered after DNA denaturation. [ABSTRACT FROM AUTHOR]