Silver Clusters of Five Atoms as Highly Selective Antitumoral Agents Through Irreversible Oxidation of Thiols

Abstract

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.

Synthesis of photocatalytic cysteine-capped Cu≈10 clusters using Cu5 clusters as catalysts

“…This equation describes accurately the size-dependent electronic structure and electronic transitions of small clusters, as was firstly demonstrated by R. M. Dickson 29,31 for Au clusters in dendrimers. Many other experimental 21,22,29,34,35 and theoretical calculations 18,31 show that this relationship between the emission and the number of atoms can be extended to Ag and Cu clusters ( i.e. clusters of highly polarizable metals) protected by weak ligands.…”

Probing the Site-Specific Reactivity and Catalytic Activity of Agn (n = 15–20) Silver Clusters

“…Furthermore, O 2 adsorption was investigated for both the singlet and triplet multiplicities for even electron clusters and doublet and quartet multiplicities for odd electron clusters. O 2 preferentially adsorbs in doublet multiplicity on the odd electron clusters and triplet multiplicity on even electron clusters expect for Ag 16 where singlet multiplicity is the favored spin state. The LANL2DZ basis set and the corresponding Los Alamos relativistic effective core potential were used for the silver atoms, and the TZVP basis set was used for carbon and oxygen atoms.…”

“…Silver in the nano and sub-nano size regime has attracted a great deal of attention due to its wide range of catalytic and optical properties. This has led to many interesting experimental studies involving the synthesis and application of silver nanoclusters for catalyzing a wide range of reactions which include NO reduction, reactions involving hydrocarbons, − and CO oxidation. − Despite the progress during the past decade to synthesize silver clusters supported on variable supports and their subsequent applications, an exact understanding of the reaction mechanism and underlying factors which govern the silver cluster reactivity is still lacking due to the complexity of heterogeneous catalysis.…”

“…NBO charge transfer to O 2 and significant spatial overlap between frontier molecular orbitals, eventually leading to their stabilization. Thus, Ag16 and Ag 18 clusters act as efficient catalysts for the environmentally important CO oxidation reaction. sı Supporting Information The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.2c01437.…”

Vibrational wave-packet dynamics of the silver pentamer probed by femtosecond NeNePo spectroscopy

“…Supported small silver clusters are at the center of current research for their remarkable photoelectric properties, high reactivity and even potential antitumoral activity. [1][2][3][4] They are also well known for their structural variability and susceptibility to slight perturbations in their environment. This variability manifests itself, for example in a competition between nearly isoenergetic three-dimensional and (quasi-)two-dimensional structures in a characteristic size range.…”