Herein, we describe a modular, stereodivergent chemoenzymatic strategy for the enantioselective total synthesis of the natural products (+)- and (-)-glabridin. A lipase-catalyzed dynamic kinetic resolution establishes the key benzylic stereocenter, while a carefully engineered protecting-group manifold preserves stereochemical integrity during fragment coupling and cyclization. From inexpensive, commercially available resorcinol-derived building blocks, the sequences deliver (-)-glabridin in 10 steps with 14% overall yield and (+)-glabridin in 12 steps with 7% overall yield. This convergent platform provides practical access to both enantiomers of glabridin and offers a general blueprint for the stereocontrolled synthesis of structurally related polyphenolic natural products.

High refractive index polymers (HRIPs) have emerged as a research focus in the development of advanced optical materials and devices. This work develops a series of thiadiazole-based polymers that exhibit high refractive indices (n D = 1.61 similar to 1.68) and satisfactory Abbe numbers (nu D = 24 similar to 46), with favorable mechanical and thermal properties. These polymers are constructed from mercaptans and biobased monomers having a thiadiazole group through a photoclick thiol-ene reaction. The optical properties of the polymers can be effectively changed by regulating the chemical structures of the monomers. For example, monomers with methoxy substituents give polymers possessing a high Abbe number but slightly low n D. On the other hand, curing groups with shorter chain lengths such as vinyl groups exhibit higher n D than those of allyl and propenyl groups with longer chain lengths. Such variations of optical properties, depending on the substituents and curing groups of the monomers, are attributed to the density of chain packing in the polymers. Density functional theory (DFT) calculations and molecular dynamics (MD) simulations are also employed for the investigation of the polarizability and molecular packing type of the polymers.

Dearomatization reactions stand as a cornerstone strategy for constructing pharmacologically pivotal saturated rings. Photoexcitation reshapes the electron distribution within the frontier molecular orbitals of aromatics, thereby unlocking dearomatization pathways inaccessible in the ground state and furnishing structurally distinct molecular motifs. Contemporary synthetic methodologies leverage three discrete mechanistic paradigms to achieve this electronic activation: direct excitation, energy-transfer photocatalysis, and exciplex formation. These precisely tuned energy-delivery modes enable the dearomatization of a diverse array of (hetero)arenes, including highly robust substrates such as naphthalenes and benzenes, under mild reaction conditions. This review spotlights recent representative advances in these excited-state transformations. We envision that this synopsis will fuel ongoing innovation in the burgeoning field of photochemical dearomatization.

Differentiating structural isomers in mass spectrometry (MS) poses significant challenges due to the difficulties in generating fragment ions by atmospheric pressure ionization and the spectral similarities encountered in tandem MS/MS analysis. The continuous arc plasma enables in-source dissociation fingerprinting analysis of isomers but presents a risk of solvent ignition during sample introduction because of high temperatures, posing safety concerns. To address these challenges, the tunable pulsed arc plasma (TPAP) ionization and dissociation device has been developed. The TPAP device converts continuous arc plasma into a pulsed mode, reduces plasma temperatures, enhances discharge stability and safety, and enables adjustable plasma energy for in-source compound dissociation. Programmable control over the pulsed arc plasma voltage allows the scanning of compounds under varying dissociation energies, facilitates the construction of compound-specific energy-resolved spectra. Validation experiments with disubstituted benzene species, chlorogenic acid derivatives, disaccharide and diacylglycerol have demonstrated the capability of TPAP-MS to effectively differentiate isomers through distinct energy-resolved spectra. The TPAP-MS requires minimal instrumental modifications and provides rapid and precise structural annotations directly from the ion source, offering broad potential applications in the analysis of structural isomers. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Core fucosylation, catalyzed by fucosyltransferase 8 (FUT8), plays critical roles in cancer progression, immune evasion, and drug resistance, making it a compelling therapeutic target. However, development of selective FUT8 inhibitors has been hindered by shared substrate specificity of fucosyltransferases. Here, we report the discovery of a previously unrecognized allosteric site on FUT8 and the development of a low-toxicity covalent inhibitor, CAIF (stearic acid-N-hydroxysuccinimide ester-dimethylimidazolium bromide), through structure-based drug design. High-throughput screening and crystallographic studies reveal that small molecules such as NH125 bind to a channel-like allosteric pocket, inducing conformational changes that disrupt FUT8 activity. Leveraging these insights, we design CAIF to covalently target lysine K216 within the allosteric site. CAIF exhibits minimal cytotoxicity and significantly inhibits core fucosylation and cancer cell invasion in cellular assays. This work establishes CAIF as a lead compound for further optimization and development, offering a framework for targeting glycosyltransferases through allosteric and covalent inhibition strategies.

N-methyl-D-aspartate-type glutamate receptors (NMDARs) initiate the synaptic plasticity underlying learning and memory. In forebrain excitatory neurons, NMDARs are heteromeric tetramers composed of two GluN1 subunits and two glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) or GluN2B subunits. At birth, NMDARs contain primarily GluN2B, but within weeks, GluN2A-containing receptors predominate the forebrain, comprising over 65% of total NMDARs in adulthood. This rapid subunit switch is essential for neonatal cognitive development, yet mechanisms driving it remain unclear. Particularly, while GluN2B levels remain relatively constant, GluN2A increases several 100-fold, despite its mRNA rising by only similar to 10-fold, strongly suggesting involvement of unknown posttranslational regulation. Here, we show that in the neonatal mouse forebrain, the linear ubiquitination axis, composed of the E3 ligase complex LUBAC and the deubiquitinase OTULIN, shifts transiently toward higher activity, with HOIP upregulated and OTULIN downregulated. In neonatal mice, experimentally reducing the axis activity by OTULIN overexpression causes persistent synaptic immaturity and adult cognitive deficits. Using proteomic and biochemical assays, we identified GluN2A as a key substrate: Linear ubiquitination at six lysines in the GluN2A C-terminus stabilizes the subunit and promotes its synaptic expression, whereas disrupting this modification destabilizes GluN2A by promoting lysosomal degradation. Consistently, overexpression of wild-type GluN2A rescues OTULIN-induced synaptic immaturity, whereas the ubiquitination-deficient GluN2A-6KR mutant fails to rescue and further exacerbates this defect. OTULIN overexpression selectively promotes GluN2A degradation, thereby delaying the GluN2B-to-GluN2A switch and synaptic maturation. These findings reveal a role for the linear ubiquitination axis in selectively stabilizing GluN2A, supporting rapid synaptic and cognitive development.

Iron(-I) remains among the least understood oxidation states of iron due to the scarcity of structurally well-defined iron(-I) complexes. Herein, we demonstrate that a combined ligand set of N-heterocyclic carbene (NHC) with divinyltetramethyldisiloxane (dvtms) can effectively stabilize iron(-I) complexes [K(18-C-6)(THF)n][(NHC)Fe(N2)(eta:2 eta 2-dvtms)] behaving like masked low-coordinate iron(-I) species in reactions. The series of iron(-I) complexes [K(18-C-6)(THF)n][(NHC)Fe(N2)(eta:2 eta 2-dvtms)] bearing different NHC ligands (NHC = I i Pr, 1a; ICy, 1b; IMesCy, 1c; IMes, 1d; IDep, 1e; IPr, 1f; Me2-cAAC, 1g) were prepared from the reactions of the iron(0) complexes [(NHC)Fe(eta:2 eta 2-dvtms)] with KC8 and 18-C-6 in THF under a dinitrogen atmosphere. These iron(-I) complexes have been characterized by 1H NMR, solution magnetic susceptibility measurement, electron paramagnetic resonance spectroscopy, elemental analysis, and single-crystal X-ray diffraction study. Reactivity studies established their conversions to the iron(I) complexes [(NHC)Fe(NNSi i Pr3)(eta:2 eta 2-dvtms)] (2), [(18-C-6)K(mu-sigma:sigma-dIDep)Fe(sigma:eta 2-MeCHSiMe2OSiMe2CH = CH2)] (3), and [K(18-C-6)(THF)2][Fe(sigma:sigma:eta:2 eta 2-CH2=CHSiMe2OSiMe2CHCH2CH2CHMe2SiOMe2SiCH = CH2)] (4) under corresponding reaction conditions, showing the capability of low-coordinate iron(-I) species in mediating two-electron reductive transformations of dinitrogen and alkenes. Furthermore, these iron(-I) complexes facilitate the hydrodehalogenation of nonactivated organic halides upon one-electron redox reactions, yielding iron(0) complexes and hydrodehalogenated organic products. The straightforward synthesis and rich reactivity of these iron(-I) complexes highlight their potential utility as reagents and catalysts for challenging chemical transformations.

The pursuit of higher energy density is central to advancing supercapacitor technology. While most existing reviews concentrate discretely on novel electrode materials or electrolytes, this work establishes a distinctive framework by linking the core device components directly to the energy density equation (E = 1/2 CV 2). We systematically dissect how the electrode, electrolyte, separator, and current collector individually and collectively influence the specific capacitance (C) and operating voltage (V). The discussion is extended to the device level, examining how symmetric and asymmetric architectures can be strategically designed to further push the energy density limits. Key topics include the engineering of high-capacitance materials such as MXenes and metal-organic frameworks, the development of wide-voltage-window electrolytes such as water-in-salt systems, and optimization of auxiliary components. This component-to-device analysis offers a holistic guide for performance enhancement, critically addresses existing limitations, and proposes informed perspectives for future research towards high-energy-density supercapacitors.

Visible-light irradiation with potassium tert-butoxide in dimethylformamide enables complete defluorination of sulfur hexafluoride under ambient conditions. Electron injection weakens the S-F bonds, producing intermediates that undergo stepwise cleavage. The process ultimately mineralizes SF6 to sulfite and fluoride salts, demonstrating a low-energy strategy for activating extremely inert fluorinated molecules.

Chiral sulfilimines are valuable sulfur-stereogenic motifs in medicinal chemistry and serve as versatile precursors to sulfoximines and sulfondiimines. Despite their importance, enantioselective S-alkylation of sulfenamides accessing to sulfilimines from abundant alkyl feedstocks remains largely unexplored, particularly via radical pathways. Herein, we report the enantioselective copper-photoredox-catalyzed S-alkylation of sulfenamides enabled by a family of amino-acid-derived N,N,N-tridentate ligands. This strategy allows the use of alkyl carboxylic acids via decarboxylative radical sulfilimination to afford enantioenriched sulfilimines in high yields and enantioselectivities. Importantly, the platform is further extended to alkyl iodides through an XAT-induced radical pathway, demonstrating the generality of this enantioselective S-alkylation manifold. A broad range of primary, secondary, and tertiary alkyl radicals, diverse sulfenamides, and complex bioactive substrates are well tolerated. Mechanistic studies support a radical process involving a stereoinvertive SH2-type substitution at a copper-sulfenamide intermediate. Gram-scale synthesis and downstream oxidation to pharmaceutically relevant sulfoximines underscore the synthetic utility of this method.

Covalent Organic Frameworks (COFs) are distinguished by their crystalline porosity and tunable optoelectronics, making them promising candidates for photocatalytic CO2 reduction. Despite this potential, optimizing the intrinsic electronic structure to facilitate efficient charge separation and substrate activation remains a critical bottleneck. Here, we report a precise strategy to modulate the electronic environment of metal centers within a porphyrin-based COF. Through an in situ linker exchange strategy on an imine-linked precursor (Im-COF-366), we successfully constructed a highly stable azo-linked framework, Azo-COF-366. The integration of azo (& horbar;N & boxH;N & horbar;) linkages serves to electronically regulate the cobalt center, effectively downshifting the conduction band and significantly enhancing charge carrier separation. Mechanistic interrogation via Density Functional Theory (DFT) and in situ DRIFTS reveals that the azo moiety enhances Co 3d-orbital splitting to lower thermodynamic barriers, a finding corroborated by the dynamic evolution of key intermediates like *HCO3 - and *COOH. Consequently, Azo-COF-366 delivers superior photocatalytic performance, achieving a CO production rate of 13.4 mmol & centerdot;g- 1 & centerdot;h- 1, which represents a dramatic improvement over the imine precursor, alongside 30% higher selectivity and exceptional chemical stability. This study establishes linker-based charge modulation as a vital tool for tailoring COF electronic states, offering new design principles for advanced solar-to-fuel technologies.

Photo-controlled block copolymer self-assembly to modulate the morphology and dimensions of polymer nanoparticles (PNPs) has attracted growing interest. However, most photo-induced polymer self-assembly approaches are dependent on ultraviolet- or visible-light-based photochemical reactions that lead to structural variations of the PNPs. The limited morphology control of these approaches hinders their broad applications. Here we report a novel near-infrared (NIR) light regulated self-seeding strategy for the controlled preparation of uniform pi-conjugated nanofibers of a 4-BBT-OPE3-P2VP22 block copolymer. This approach combines a NIR light induced photothermal effect with living crystallization-driven self-assembly (CDSA). By taking advantage of excellent photothermal activity and crystallinity of the 4-BBT-OPE3 segment, uniform helical fiber-like micelles could be generated with tunable lengths from similar to 40 nm to 1.1 & micro;m, photothermal activity and NIR-II emission. The lengths of these fiber-like micelles could be regulated by the time and power of NIR irradiation (808 nm laser). Moreover, the NIR light regulated self-seeding strategy could also be extended to core-crystalline block copolymers that lack a NIR-absorbing group if a NIR-absorbing dye like indocyanine green was added to the solution. Given the appealing merits and versatility of NIR light regulated self-seeding, this work paves a new way toward precise preparation of smart functional nanomaterials.

Systemic light chain amyloidosis (AL) is characterized by amyloid fibril deposition in multiple organs, often severely affecting cardiac function. In this study, we extracted amyloid fibrils directly from abdominal fat and cardiac tissue biopsies obtained from three AL patients. Using cryo-electron microscopy, we determined five distinct structures of light chain (LC) amyloid fibrils. Our results demonstrate that LC fibrils from different patients adopt unique structural conformations, highlighting patient-specific fibril variations. Conversely, LC fibrils extracted from different tissues within the same patient share highly similar overall fibril structures, yet exhibit localized conformational variations, potentially shaped by distinct environmental cofactors. This study emphasizes the combined roles of patient-specific protein sequences and tissue-specific microenvironments in defining LC fibril conformation. The determination of LC fibril structures directly from easily accessible abdominal fat biopsy provides critical molecular insights into AL amyloidosis pathology, facilitating the development of therapeutic strategies.

OSCA/TMEM63 mechanosensitive ion channels play critical physiological roles in plants and animals. These channels bear structural homology to the dual functional TMEM16 family, and OSCA1.2 was recently shown to form a lipid-lined ion conduction pathway in the open state. This raised the question of whether members of the OSCA/TMEM63 family may also function as mechanically activated lipid scramblases. Using a combination of in vitro and cellular assays with computational techniques, we show that phospholipids can be translocated through the open pores of OSCA1.1/1.2/2.2 and TMEM63A/B proteins, suggesting a dual ion channel and lipid scramblase function for members of this protein family. We characterize the effects of mutating key groove lining residues demonstrating that different residues form bottlenecks for lipids and ions respectively and show that cholesterol inhibits lipid scrambling by stabilizing the closed state and slowing translocation through the open pore. We show that lipid scrambling in TMEM63 proteins can be activated by mechanical forces in the membrane, making these mechanically activated lipid scramblases. Finally, we demonstrate that this activity is important for the mechanically induced morphological remodeling of biological membranes and the resilience of cells to high mechanical forces.