JACS Au最新文献

Supersulfides are rising stars in regulating redox. Their distinctive redox biological functions are becoming increasingly evident with the advancement of supersulfide donors. However, most existing donors are limited to releasing hydropersulfide (RSSH) only, and in addition, there is still a knowledge gap in translating supersulfides into therapeutic molecules. To this end, in this work, we devised and synthesized a supersulfide donor-drug conjugate, RSSS-ASA, containing an azo moiety. This bifunctional prodrug enables the production of hydrotrisulfide (RSSSH) catalyzed by intestinal azoreductase, accompanied by the release of the anti-inflammatory molecule 5-aminosalicylic acid (ASA). Notably, the corelease of the supersulfides with ASA exhibited colonic-targeting attributes, thereby synergistically contributing to the potent anti-inflammatory and antioxidant activities observed in cellular and animal models. This prodrug design is worthy of further development and translation in donor development and disease treatment.

Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses the strength, type, and duration of stress to balance cell survival and death through an unknown mechanism. Recently, changes in the physical property of Hsf1 condensates due to persistent stress have been suggested to trigger apoptosis, highlighting the importance of biological phase separation and transition in cell fate decisions. In this study, the mechanism underlying Hsf1 droplet formation and oxidative response was investigated through 3D refractive index imaging of the internal architecture, corroborated by molecular dynamics simulations and biophysical/biochemical experiments. We found that, in response to oxidative conditions, Hsf1 formed liquid condensates that suppressed its internal mobility. Furthermore, these conditions triggered the hyper-oligomerization of Hsf1, mediated by disulfide bonds and secondary structure stabilization, leading to the formation of dense core particles in the Hsf1 droplet. Collectively, these data demonstrate how the physical property of Hsf1 condensates undergoes an oxidative transition by sensing redox conditions to potentially drive cell fate decisions.

Supersulfides are rising stars in regulating redox. Their distinctive redox biological functions are becoming increasingly evident with the advancement of supersulfide donors. However, most existing donors are limited to releasing hydropersulfide (RSSH) only, and in addition, there is still a knowledge gap in translating supersulfides into therapeutic molecules. To this end, in this work, we devised and synthesized a supersulfide donor–drug conjugate, RSSS–ASA, containing an azo moiety. This bifunctional prodrug enables the production of hydrotrisulfide (RSSSH) catalyzed by intestinal azoreductase, accompanied by the release of the anti-inflammatory molecule 5-aminosalicylic acid (ASA). Notably, the corelease of the supersulfides with ASA exhibited colonic-targeting attributes, thereby synergistically contributing to the potent anti-inflammatory and antioxidant activities observed in cellular and animal models. This prodrug design is worthy of further development and translation in donor development and disease treatment.

Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses the strength, type, and duration of stress to balance cell survival and death through an unknown mechanism. Recently, changes in the physical property of Hsf1 condensates due to persistent stress have been suggested to trigger apoptosis, highlighting the importance of biological phase separation and transition in cell fate decisions. In this study, the mechanism underlying Hsf1 droplet formation and oxidative response was investigated through 3D refractive index imaging of the internal architecture, corroborated by molecular dynamics simulations and biophysical/biochemical experiments. We found that, in response to oxidative conditions, Hsf1 formed liquid condensates that suppressed its internal mobility. Furthermore, these conditions triggered the hyper-oligomerization of Hsf1, mediated by disulfide bonds and secondary structure stabilization, leading to the formation of dense core particles in the Hsf1 droplet. Collectively, these data demonstrate how the physical property of Hsf1 condensates undergoes an oxidative transition by sensing redox conditions to potentially drive cell fate decisions.

Many important synthetic-oriented works have proposed excited organic radicals as photoactive species, yet mechanistic studies raised doubts about whether they can truly function as photocatalysts. This skepticism originates from the formation of (photo)redox-active degradation products and the picosecond decay of electronically excited radicals, which is considered too short for diffusion-based photoinduced electron transfer reactions. From this perspective, we analyze important synthetic transformations where organic radicals have been proposed as photocatalysts, comparing their theoretical maximum excited state potentials with the potentials required for the observed photocatalytic reactivity. We summarize mechanistic studies of structurally similar photocatalysts indicating different reaction pathways for some catalytic systems, addressing cases where the proposed radical photocatalysts exceed their theoretical maximum reactivity. Additionally, we perform a kinetic analysis to explain the photoinduced electron transfer observed in excited radicals on subpicosecond time scales. We further rationalize the potential anti-Kasha reactivity from higher excited states with femtosecond lifetimes, highlighting how future photocatalysis advancements could unlock new photochemical pathways.

Many important synthetic-oriented works have proposed excited organic radicals as photoactive species, yet mechanistic studies raised doubts about whether they can truly function as photocatalysts. This skepticism originates from the formation of (photo)redox-active degradation products and the picosecond decay of electronically excited radicals, which is considered too short for diffusion-based photoinduced electron transfer reactions. From this perspective, we analyze important synthetic transformations where organic radicals have been proposed as photocatalysts, comparing their theoretical maximum excited state potentials with the potentials required for the observed photocatalytic reactivity. We summarize mechanistic studies of structurally similar photocatalysts indicating different reaction pathways for some catalytic systems, addressing cases where the proposed radical photocatalysts exceed their theoretical maximum reactivity. Additionally, we perform a kinetic analysis to explain the photoinduced electron transfer observed in excited radicals on subpicosecond time scales. We further rationalize the potential anti-Kasha reactivity from higher excited states with femtosecond lifetimes, highlighting how future photocatalysis advancements could unlock new photochemical pathways.

Dynamic DNA nanostructures that reconfigure into different shapes are used in several applications in biosensing, drug delivery, and data storage. One of the ways to produce such structural transformations is by a process called strand displacement. This laboratory experiment demonstrates a strand displacement reaction in a two-stranded DNA nanostructure called switchback DNA by the addition of a third strand. In this process, the difference in the affinity between the component DNA strands is used to convert switchback DNA into conventional duplex DNA. Students are introduced to the concept through gel electrophoresis and quantitative analysis of DNA nanostructure reconfiguration. The experiment presented here is an example of DNA nanotechnology-based exercises in an undergraduate setting and is tailored for adaptation in a chemistry, biology, or biochemistry laboratory with minimal costs.

The replacement of a noble metal catalyst by base metals presents a great challenge for low-temperature CO and volatile organic compounds oxidation. Cu/Ce-based catalysts are expected to achieve this goal with excellent performance, among which the main active sites still need to be further explored. For this reason, CuCe catalysts were further compounded with typical elements (cobalt, Co) to study the main active sites and compositing effect by in-situ enhanced Raman and in-situ ultralow-temperature DRIFTS technologies. The main active site for both CuCe and CuCoCe catalysts was the same Cu-O_V-Ce at the copper-cerium interface, named as asymmetric oxygen vacancy (ASOv). The dispersion of CuO and CeO₂ species was promoted, and the formation energy of ASOv was decreased significantly from 1.502 to 0.854 eV after the addition of Co, which leads to an increase in the ASOv concentration. A small cobalt added can form more Co²⁺ species, improving the activity and stability. The activity of Cu₁Co_0.5Ce₃ catalyst was significantly improved with 100% conversion of CO and toluene at 96 and 227 °C. Here, the ASOv was studied in relative quantification, showing consistency of catalytic activity and ASOv concentration. Meanwhile, the dynamic exchange of ASOv in the reactions was tracked, indicating that the redox equilibrium of ASOv can continuously produce new ASO_V in Cu/Ce-based catalysts that cause long-term catalytic stability. In addition, it is almost difficult for CoCe and CoCu samples to form the ASOv, and the interaction between metals and metals was also weaker than that of CuCe and CuCoCe catalysts.

The N-heterocyclic carbene (NHC)-catalyzed umpolung of aldimines using quinoxalin-2-ones for intermolecular reactions is demonstrated. Specifically, NHC-catalyzed cross-coupling of quinoxalin-2-ones with isatins proceeds via the generation of aza-Breslow intermediates by the addition of carbene to the C=N moiety of quinoxalinones followed by interception with isatins to afford diverse oxindoles in moderate to good yields and good functional group compatibility. Moreover, detailed mechanistic studies involving the isolation and characterization of the imidoyl azoliums (oxidized form of the aza-Breslow intermediates) are provided. Considering the significance of scaffolds bearing both quinoxalin-2-one and oxindole moieties in medicine and natural products, the synthesized molecules employing the NHC-catalyzed imine umpolung strategy are likely to find promising applications.

Dynamic DNA nanostructures that reconfigure into different shapes are used in several applications in biosensing, drug delivery, and data storage. One of the ways to produce such structural transformations is by a process called strand displacement. This laboratory experiment demonstrates a strand displacement reaction in a two-stranded DNA nanostructure called switchback DNA by the addition of a third strand. In this process, the difference in the affinity between the component DNA strands is used to convert switchback DNA into conventional duplex DNA. Students are introduced to the concept through gel electrophoresis and quantitative analysis of DNA nanostructure reconfiguration. The experiment presented here is an example of DNA nanotechnology-based exercises in an undergraduate setting and is tailored for adaptation in a chemistry, biology, or biochemistry laboratory with minimal costs.