Science China Chemistry最新文献

Proteolysis targeting chimeras (PROTACs) have been considered a promising therapeutic strategy, but their application is restricted by the limited number of available E3 ligases. Here, we expanded Parkin, an autoinhibitory E3 whose activity can be triggered by binding to its activating ligand, phosphorylated ubiquitin (Ub^P), into the repertoire of E3 ligases for targeted protein degradation (TPD). Specifically, we rationally designed a Parkin-activating ligand Ub^P-M based on Ub^P and conjugated it with small-molecule binders against target proteins such as Brd4 and SF3B1 using total chemical synthesis. These degraders successfully induced ubiquitination and degradation of target proteins. Notably, conjugating small-molecule binders of Brd4 and SF3B1 together to Ub^P-M simultaneously targets both proteins for degradation. As a proof-of-concept, our studies demonstrate the potential of Parkin as a potential E3 ligase for PROTACs, providing a new framework for developing targeted degraders via dynamic activation mechanisms.

Boron, positioned to the left of carbon in the periodic table with one fewer electron, exhibits unique chemical properties. Tricoordinate boron compounds are typically electron-deficient, acting as strong Lewis acids in general with electrophilic behavior. In contrast, tetracoordinate boron compounds, featuring a tetrahedral geometry, display nucleophilicity and enable transformations such as migration, transmetallation, and oxidation. Boron compounds serve as versatile synthons, reagents, and catalysts in organic reactions. Incorporating boron into conjugated systems enhances chemical diversity and modulates optoelectronic properties, while the vacant p orbital of boron imparts high electron affinity and unique stimulus-responsive characteristics. Additionally, boron forms deltahedral clusters in polyhedral (car)boranes, which are air-and moisture-stable and distinct from traditional hydrocarbon structures. This review provides an overview of the fundamental properties and diverse applications of boron compounds across various fields.

Cyclic peptides, with their unique structures and versatile biological activities, hold great potential for combating skin aging issues such as wrinkles, laxity, and pigmentation. However, traditional discovery methods relying on iterative synthesis and screening are labor-intensive and resource-intensive. Here, we present an integrated platform combining automated rapid cyclopeptide synthesis, virtual screening, and biological activity assessment, enabling the transformation of designed cyclic peptide sequences into chemical entities within minutes with high crude purity. Using ADCP docking with the ADFR suite, we identified a series of novel cyclic peptides targeting JAK1, Keap1, and TGF-β proteins. Among these, MKC1 demonstrated optimal anti-aging efficacy, as evidenced by its reactive oxygen species (ROS) scavenging activity (20%) and significant upregulation of type I collagen genes (Col1a1a: 156%, Col1a1b: 87%, Col1a2: 103%) and elastin (Elna: 132%) at a concentration of 0.001%. This study establishes a robust foundation for the discovery and development of cyclic peptides as antiaging active compounds.

Suppressing the dark current density in organic diodes is essential for developing practical consumer electronics such as in-door photovoltaics and photodetectors. While extensive research has explored dark current from thermodynamics and kinetics (of free and trapped charges) perspectives, a clear relationship between nanostructure and dark current remains elusive. In this contribution, the relationship between the structural/morphological order of non-fullerene acceptors (NFAs) with the dark current and shunts in their organic photodetectors (OPDs) is investigated. Starting with the state-of-the-art NFA C9-12 (BTP-eC9), we systematically tune the molecular structural symmetry and alkyl chain length. We find that unsymmetrizing the end groups and/or extending the alkyl chains of NFAs leads to swollen intermolecular packing in solid state, effectively suppressing microscopic shunting paths. Additionally, increasing alkyl chain length promotes more oriented intermolecular packing in the out-of-plane direction, reducing energetic disorder and consequently suppressing the thermal generation of dark charges. These combined benefits lead to a simultaneous suppression of both thermally activated diode current and shunt current in OPDs based on unsymmetrical non-fullerene acceptors with long alkyl chains.

Cost-effective metal-based electrocatalysts are desirable for industrial water and seawater electrolysis, triggering the hydrogen evolution reaction (HER) with high efficiency. Here, we report the loading of ultralow-content Ru-Os dual-atom onto NiCoP nanoneedles significantly enhancing HER in seawater splitting. The localization of 0.16% Ru and 0.58% Os atoms within NiCoP induces changes in the electronic structure and coordination environment of the Ni active sites. This catalyst achieves low overpotentials (29 and 303 mV in alkaline solution, 68 and 331 mV in alkaline seawater) at 10 and 800 mA/cm², respectively, demonstrating remarkable stability by maintaining performance at 500 mA/cm² for 24 h in alkaline and simulated seawater. Experimental and theoretical studies indicate that ultralow content Ru and Os dual atoms are immobilized on the surface of NiCoP/NF through Ru-P and Os-P bonds, leading to electron transfer and changes in the coordination environment. These results enhance the activity of Ni active sits on support, demonstrating superior HER performance in alkaline solution and seawater. Ultralow content Ru and Os dual atoms in NiCoP@Ru-Os/NF play a crucial role in reducing the Gibbs free energy of hydrogen adsorption and lowering the d-band position of the catalyst, thereby accelerating the HER kinetic.

Asymmetric direct hydrogenation (ADH) is a straightforward and atom-economic methodology to achieve optically active compounds. The synthesis of chiral compounds bearing stereogenic centers has been well established. In contrast, the construction of atropisomers, especially atropisomers bearing multiple chiral elements, has sporadically been explored. Herein, we report an innovative atroposelective iridium-catalyzed hydrogenation of N-arylindole ketones and heterobiaryl ketones via dynamic kinetic resolution (DKR) based on a Lewis acid-base interaction between the nitrogen atom and the carbonyl group of ketones, providing C-N and C-C atropisomers bearing multiple chiral elements with excellent enantioselectivities, diastereoselectivities and yields. The lynchpin of the DKR-ADH process stands in the newly developed planar-chiral tridentate PNO ligand, which ensures the excellent control of enantioselectivity and diastereoselectivity simultaneously. The synthetic utilization of this protocol is proved through stereospecific transformation to a tridentate PNN ligand bearing axial and central chirality, which shows promising potential in iridium-catalyzed asymmetric hydrogenation of simple ketones.

Developing chiral thermally activated delayed fluorescence (TADF) materials with excellent photophysical and chiroptical properties is crucial for advancing circularly polarized organic light-emitting diodes (CP-OLED). To overcome the inherent trade-off relationship between photoluminescent quantum yield (PLQY) and dissymmetry factor (g), a fixed degenerate exciton chirality (FD-EC) strategy based on the multiple resonance TADF chromophore is proposed, exhibiting improved deep-blue emission with the peak at 454 nm and a high PLQY of 0.96, and unique exciton chirality with amplified |g_abs| and |g_PL| values of 1.0 × 10^-3 and 1.6 × 10^-3. The CP-OLED, incorporating the chiral blue emitter, exhibits standard blue emission with a narrow full width at half maximum of 30 nm, a superior external quantum efficiency of 27.8%, Commission Internationale de L’Eclairage coordinates of (0.14, 0.08), and distinct circularly polarized electroluminescence.

The functionalization of alkenes is a practical and important approach to access high value-added compounds. We herein realized the combination of energy transfer (EnT) and hydrogen atom transfer (HAT) process for the in situ giving acyl azolium ions from the acyl electrophiles and N-heterocyclic carbenes (NHCs) catalysts under light irradiation, and developed three-component radical relay-type alkylacylation of readily available alkenes promoted by the cooperative NHC-photo cocatalysis to access structurally diversified alkylacylation products. The unique strategy for the NHC catalyst-bound acyl azoliums working as the intermolecular HAT reagent with the EnT process was revealed. This protocol was also utilized to enable the late-stage functionalization of some important drugs and bioactive molecules. It featured readily bifunctionalization of alkenes, a wide range of alkenes and acyl imidazoles, mild reaction conditions, excellent selectivity, as well as broad functional group compatibility. Scale-up synthesis and a list of derivatization reactions displayed the potential synthetic application. Control experimental investigations and computational studies support that it involved the photoexcitation of in situ forming acyl azolium ions via EnT process to access triplet diradical species with facile intersystem crossing, and acted as HAT reagents to undergo intermolecular HAT process, and then engaged in the following radical addition/radical-radical cross-coupling reaction with NHCs-linked radicals, resulting in alkylacylation products promoted by cooperative NHC and photocatalysis.

Chiral phosphorescent manganese (Mn(II)) complexes hold application promise in circularly polarized organic light-emitting diodes (CP-OLEDs) and three-dimensional (3D) display technologies due to their CP luminescence properties, but that simultaneously exhibit both high dissymmetry factors (g_PL) and photoluminescence quantum yields (PLQYs) remain rare. In this study, we report planar chiral Mn(II) enantiomers, R/S-PhCyPO-MnBr₂ and R/S-DPhPO-MnBr₂, based on [2.2]paracyclophane phosphine oxide ligands, which demonstrate green photoluminescence with high PLQYs of 90% and 88%, and high |gPL| values of 4.2 × 10⁻³ and 4.0 × 10⁻³, respectively. Notably, the PhCyPO-MnBr₂-based OLED achieves a record-high maximum external quantum efficiency of 16.0% among those with Mn(II) complexes. Furthermore, CP-OLEDs incorporating these enantiomers exhibit electroluminescence peaking at 518 and 527 nm, with |g_EL| factors of 4.5 × 10⁻³ and 4.3 × 10⁻³, respectively. This study provides a novel approach for the design of chiral Mn(II) complexes for high-performance CP-OLEDs.