Disentangling Competitive and Synergistic Chemical Reactivities During the Seeded Growth of High-Entropy Alloys on High-Entropy Metal Sulfide Nanoparticles.

The seeded growth of one type of nanoparticle on the surface of another is foundational to synthesizing many multifunctional nanostructures. High-entropy nanoparticles that randomly incorporate five or more elements offer enhanced properties due to synergistic interactions. Incorporating high-entropy nanoparticles into seeded growth platforms is essential for merging their unique properties with the functional enhancements that arise from particle-particle interactions. However, the complex compositions of high-entropy materials complicate the seeded growth process due to competing particle growth and chemical reactivity pathways. Here, we design and synthesize a 36-member nanoparticle library to identify and disentangle these competitive interactions, ultimately defining chemical characteristics that underpin the seeded growth of high-entropy alloys on high-entropy metal sulfide nanoparticles. As a model system, we focus on (Cu,Zn,Co,In,Ga)S-SnPdPtRhIr, which combines a high-entropy metal sulfide semiconductor with a high-entropy alloy catalyst. We study the seeded growth of all possible pairwise combinations of Sn, Pd, Pt, Rh, Ir, and SnPdPtRhIr on the metal sulfides Cu1.8S, ZnS, Co9S8, CuInS2, CuGaS2, and (Cu,Zn,Co,In,Ga)S, which have comparable morphologies and sizes. Through these studies, we uncover unexpected chemical reactivities, including cation exchange, redox reactions, and diffusion. Reaction temperature, threshold reduction potentials, metal/sulfide chemical reactivity, and the relative strengths of the various bonds that could be formed during particle growth emerge as the primary factors that underpin seeded growth. Finally, we disentangle these competitive and synergistic chemical reactivities to generate a reactivity map that provides practical guidelines for achieving seeded growth in compositionally complex systems.

The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage.

The DNA damage response network stimulates microRNA (miRNA) biogenesis to coordinate repair, cell cycle checkpoints, and apoptosis. The multistep process of miRNA biogenesis involves the cleavage of primary miRNAs by the microprocessor complex composed of the ribonuclease Drosha and the RNA binding protein DGCR8. We found that the tyrosine kinase ABL phosphorylated DGCR8, a modification that was required for the induction of a subset of miRNAs after DNA damage. Focusing on the miR-34 family, ABL stimulated the production of miR-34c, but not miR-34a, through Drosha/DGCR8-dependent processing of primary miR-34c (pri-miR-34c). This miRNA-selective effect of ABL required the sequences flanking the precursor miR-34c (pre-miR-34c) stem-loop. In pri-miRNA processing, DGCR8 binds the pre-miR stem-loop and recruits Drosha to the miRNA. RNA cross-linking assays showed that DGCR8 and Drosha interacted with pri-miR-34c, but we found an inverse correlation between ABL-stimulated processing and DGCR8 association with pri-miR-34c. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267). Ectopic expression of a Y267F-DGCR8 mutant reduced the recruitment of Drosha to pri-miR-34c and prevented ABL or Drosha from stimulating the processing of pri-miR-34c. In mice engineered to express a nuclear import-defective mutant of ABL, miR-34c, but not miR-34a, expression was reduced in the kidney, and apoptosis of the renal epithelial cells was impaired in response to cisplatin. These results reveal a new pathway in the DNA damage response wherein ABL-dependent tyrosine phosphorylation of DGCR8 stimulates the processing of selective primary miRNAs.