A general method for enantioselective silylation of both aromatic and aliphatic alpha,beta-unsaturated phosphine oxide derivatives remains elusive. Herein, we report a versatile enantioselective conjugate silylation protocol enabled by newly developed N -heterocyclic carbenes. Under copper(I)-YC-NHC7 catalysis, a wide range of aromatic and aliphatic alkenylphosphine oxides undergoes efficient conjugate silylation, affording structurally diverse beta-silylated alkylphosphine oxide derivatives with moderate to high yields and enantioselectivities.

Skeleton rearrangement involving carbocation species is an enabling class of organic transformations. It has found great utility in the synthesis of advanced target molecules with complex structures and hindered stereogenic centers. Regulating the pathways for the transformations of highly reactive carbocation intermediates, such that the skeleton rearrangement takes place in a selective manner, is highly desirable but challenging. Herein we report the divergent assembly of a series of chiral polycyclic molecules based on selective transformations of bridged-ring phenonium-like intermediates that are readily generated via asymmetric electrophilic dearomatization of indoles with o-chloranil/o-quinone dibenzimides followed by aza-Prins-type cyclization. The initial step of such cascade reactions is promoted by chiral phosphoric acid catalysts, while the downstream generation and transformation of the phenonium-like intermediates are facilitated by additional acid additives. Target molecules with diverse polycyclic structures are obtained in good yields (up to 97%) with high enantioselectivity (up to >99% ee). The energy profiles and asymmetric induction models of these reactions are revealed by comprehensive DFT calculations.

The difluoromethylene (-CF2-) motif is highly valuable in pharmaceuticals, agrochemicals, and materials science due to its unique physicochemical properties. Herein, we present a broadly applicable strategy for the modular synthesis of CF2-containing compounds by using difluoromethylene to bridge electrophiles and electronically diverse alkenes, with difluoromethyl phenyl sulfone (PhSO2CF2H) as the difluoromethylene source. Central to this approach is the activation of (phenylsulfonyl)difluoromethylated derivatives (PhSO2CF2R) by the excited-state Hantzsch ester anion (HE-), which enables efficient generation of difluoroalkyl radicals under mild conditions. This method exhibits broad substrate scope, accommodating electron-rich, neutral, and deficient alkenes, as well as a wide range of difluoroalkyl sulfones derived from alkyl halides, cyclic sulfates, and carbonyl compounds. Furthermore, we developed a simplified operational protocol that circumvents the need for pre-preparation of PhSO2CF2R. Mechanistic studies support a radical pathway initiated by single-electron transfer between the photoexcited HE- and PhSO2CF2R. Practical applications are demonstrated through gram-scale syntheses and late-stage modification of bioactive molecules and functional materials, establishing a versatile platform for constructing a wide range of difluoromethylene-containing compounds.

A novel class of chiral tert-butylsulfinyl-oxazoline (tBu-SOX) ligands, which feature stereospatial control achieved by directly introducing a bulky group at the sulfur center, was prepared. This series of ligands can be conveniently synthesized via lithiation of chiral ortho-bromooxazoline compounds followed by reaction with chiral tert-butyl tert-butanethiosulfinate. In palladium-catalyzed asymmetric allylic alkylation, these ligands exhibited excellent catalytic performance, delivering up to 99% yield and 99% enantioselectivity. Further X-ray crystallographic analysis confirmed the well-defined chiral spatial configuration of the corresponding Pd(II) complex. The results demonstrate that steric modulation at the sulfur center is an effective strategy for advancing the design of sulfinyl-oxazoline chiral ligands.

Biological ion channels regulate ion flux through gating and blockade, yet translating such precise kinetic control into discrete synthetic containers remains a fundamental challenge in supramolecular chemistry. Here we report a bioinspired calix[4]trap ion container engineered with a crown ether binding site at its aperture to implement ion controlled gating. Specifically, K+ and NH4+ occupy a deeply buried pocket, whereas Cs+ preferentially and exclusively binds at the entrance, acting as a removable gatekeeping ion that restricts access to the cavity. Consequently, Cs+ bound at the entrance hinders both ion encapsulation and release, enabling direct observation of otherwise rapid uptake processes and providing a quantitative handle to decelerate release. Importantly, the release kinetics are strictly decoupled from the thermodynamic driving force. The release rate is governed by the concentration of the gatekeeping Cs+ rather than the stoichiometric amount of the chemical trigger (DBU). This allows for sustained and programmable ion release over hours through a simple stoichiometric input. This minimal noncovalent gatekeeping strategy offers a general blueprint for designing tunable ion carrier containers and programmable biomimetic transport systems.

A ring-opening three-component reaction of carboxylic acid, a cyclic (thio)ether and a difluorocarbene precursor Ylide-CF2H was reported, affording difluoromethyl(thio)ethers in good yields. The reaction proceeds under simple and mild conditions, with good substrate compatibility. Although the mechanism remains speculative, a proposed pathway involves the initial activation of the Ylide-CF2H species through protonation of the malonate moiety, leading to the generation of difluorocarbene. Nucleophilic attack of difluorocarbene by the cyclic (thio) ether forms an oxonium ylide or sulfonium ylide, which undergoes protonation followed by nucleophilic attack of the alpha-carbon of the intermediate to afford the difluoromethyl(thio)ethers. Additionally, by switching the solvent to toluene, a direct difluoromethylation of carboxylic acids was observed, which provides an alternative transformation under modified conditions.

Direct propylene copolymerization with short-chain 2-vinylacetic acid (VA) offers an appealing yet elusive route to carboxylic acid-functionalized propylene copolymers. However, it has been hampered by severe catalyst deactivation arising from the strong sigma-donor/chelating coordination of the acid functionality. Herein we report propylene copolymerization with VA in the presence of Et2AlCl using binuclear nickel catalyst system and achieved a 5-minute activity up to 1.147 & times; 10(6) g/(mol cat & sdot;h). By modifying substituents (R-1 and R-2) on the binuclear ligand framework, efficient modulation over propylene insertion regiochemistry and chain walking is achieved, enabling the on-demand access to two distinct acid-functionalized polyolefin classes: polypropylene copolymers (suppressed chain walking, high methyl branching) and ethylene-propylene rubber-like (EPR-like) copolymers (extensive chain walking, low glass transition temperature). NMR microstructural analysis of the two types of P/VA copolymer reveal branching densities of 298 similar to 333 branches/1000 carbons and 126 similar to 223 branches/1000 carbons, respectively. Complementary DFT calculations attribute this divergent microstructure control to catalyst-structure-dependent energetic competition between 1,2- and 2,1-insertion, as well as chain walking within the confined binuclear steric environment.

Costimulatory receptors of the TNFR superfamily are key components in synthetic immunoreceptors, yet how their intracellular domains coordinate membrane anchoring with adaptor recruitment remains unresolved. Here, using solution-state NMR and membrane-reconstituted FRET assays, we identify a conserved basic-residue-rich sequence (BRS) in the juxtamembrane region of OX40 that binds anionic phospholipids and adopts a membrane-inserted conformation. This membrane engagement enables a dual-site interaction with TRAF2, combining canonical PxQxx binding with a secondary membrane-proximal interface, to promote robust NF-kappa B activation. Disruption of the BRS impairs adaptor docking without reducing receptor surface expression or ligand-induced clustering. This regulatory architecture is further supported in 4-1BB and CD40, indicating broader relevance across TNFR costimulatory receptors. Our findings refine current models of TNFR signaling and offer a generalizable framework for receptor design. Incorporating membrane-anchoring motifs into synthetic constructs may enhance spatial control of adaptor recruitment, thereby improving signal fidelity, sensitivity, and performance in CAR-T applications.

Conjugated enones feature diverse structures and wide availability. Their asymmetric double (transfer) hydrogenation serves as an efficient strategy for the construction of secondary alcohols with multiple chiral centers. However, such transformations are highly challenging, as it requires the catalytic system to reduce two distinct types of unsaturated bonds while achieving precise control over multiple stereoselectivities. In recent years, remarkable progress has been made in this field through the development of new ligands and catalysts, the utilization of bimetallic relay catalytic systems, and the regulation of catalytic processes by additives. Based on the structural characteristics of conjugated enones, the advances in transition-metal-catalyzed asymmetric double hydrogenation and asymmetric double transfer hydrogenation of conjugated enones are summarized. The key challenges and future prospects in this area are also outlined and discussed.

Metabolite annotation, especially the discovery of unknown metabolites, remains a fundamental challenge in mass spectrometry-based untargeted metabolomics due to limited reference mass spectra. Here we present MetGenX, a structure-informed encoder-decoder neural network that enables efficient and controllable generation of metabolite structures directly from MS2 spectra. By reformulating the spectrum-to-structure task as a structure-to-structure generation problem, MetGenX significantly improves generation accuracy and chemical space coverage. In independent tests, it achieved top-1 accuracy of 55.9% on 1388 NIST MS2 spectra and 68.5% on 1681 spectra from real biological samples, outperforming existing in silico tools. Its structure-informed design ensures robust performance across both positive and negative ionization modes without retraining. Applying a multi-step annotation workflow to mouse liver untargeted metabolomics data, MetGenX identified two previously uncharacterized metabolites absent from major human metabolome databases. These results demonstrate MetGenX's strong potential to advance de novo metabolite annotation and facilitate the discovery of uncharacterized chemical entities.

Surfactants, as a class of important functional compounds, are widely used in daily chemicals, biomedicine, petroleum extraction, and other fields. However, the traditional trial-and-error experimental approach not only struggles to meet the performance requirements of novel surfactants under extreme conditions but also lacks systematic evaluation of their environmental fate and biosafety. Machine learning, as a data-driven research paradigm, offers a novel approach for efficient surfactant development, demonstrating significant potential particularly in molecular property prediction. This article systematically reviews advances in machine learning for predicting key surfactant properties (e.g., critical micelle concentration, surface tension, hydrophilic-lipophilic balance, adsorption efficiency, and Krafft point). Furthermore, it examines preliminary applications and prospects of this technology in predicting environmental safety parameters such as biodegradability and ecotoxicity. Current research predominantly focuses on predicting critical micelle concentration, surface tension, and hydrophilic-lipophilic balance, whereas modeling studies on adsorption efficiency, Krafft point, and environmental safety parameters remain relatively limited. By extending predictive capabilities to these underexplored properties, machine learning is poised to become a pivotal tool for rational design, performance optimization, and green assessment of surfactants, thereby advancing the development of high-performance and environmentally friendly surfactants.

Different from broadly studied metal walking strategy as a powerful way to realize remote C-H activation of alkenes, process for alkyne walking and functionalization remains unexplored. Similarly, alkyne hydrofunctionalization exclusively focuses on in situ transformation, while related remote protocol is unknown. Here we describe a proof-of-concept study on migratory alkyne functionalization. Three types of alkynes and two types of nucleophiles are adopted to realize the migratory hydroalkylation and hydroamination of alkynes with good stereocontrol, which also represents a potential route for the asymmetric activation of three continuous inert C(sp3)-H bonds. Gram-scale test and downstream transformations highlight the reliability and practical value of the concept. Mechanistic studies including calculations uncover a featured 1,3-diene formation-driven allylic C(sp3)-C(sp3) bond transposition process, which enables the stereoconvergence of undesired regioisomers from competitive in situ hydrofunctionalization into consistent migration products.

Herein, a multiphase interfacial polymerization strategy has been developed to controllably fabricate Ato-B type Janus covalent organic framework (COF) membranes with asymmetric properties. This approach allows one-pot construction of heterostructured COF membranes with opposite wettability on the upper and lower surfaces via integrating simultaneous but independent interfacial polymerizations at two interfaces of a three-phase system. Being integrated two distinct two-dimensional COF layers with the same frame structure but differing in side chains, the Janus COF membranes exhibits hydrophilic feature on one side but displays hydrophobic characteristic on the other side. Additionally, the Janus COF membranes exhibit exceptional anti-pollution performance and exclusively permits unidirectional water transport. Notably, this unique property is non-designable in the homogeneous COF membranes fabricated from the same building blocks via the conventional two-phase interfacial polymerization method. The Janus membranes were further demonstrated to be a good candidate for membrane desalination with a high rejection for MgSO4 . This novel multiphase interfacial polymerization strategy offers a general way to fabricate Janus membranes with designable, predictable, and controllable asymmetric properties from a wide range of materials, holding great potential for diverse applications. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

The construction of polymer/ceramic composite electrolytes has significantly enhanced ionic conductivity and alleviated electrolyte-electrode interfacial contact, representing a promising strategy for tackling the challenges of ambient-temperature lithium-metal-based solid-state batteries (SSBs). However, the critical issue of impeded ion transport at the polymer-ceramic interphase within these composites remains unresolved. Polymers provide chemical compatibility yet suffer from intrinsically low conductivity, whereas ceramics exhibit high conductivity yet suffer from interfacial reactivity. Blending the two often yields heterogeneous composites in which Li+ transport is blocked at poorly connected polymer-ceramic interphases, preventing continuous ion flux and hindering room-temperature cycling. Here, we overcome this interphasial bottleneck by chemically bonding polymers to ceramic surfaces via a surface-initiated polymerization strategy, thereby creating a molecularly integrated hybrid electrolyte. Direct electrochemical evidence showed that chemical bonding substantially suppresses polymer-ceramic interphasial impedance and reduces electrode-electrolyte interfacial resistance. The resulting continuous Li+ transport pathways yielded a conductivity of 1.1 & times; 10-4 S cm-1 at 30 degrees C, 4 times that of mixed composites, enabling dendrite-free Li plating for 1,200 h alongside stable ambient-temperature SSB operation. These findings elucidate how interfacial chemistry modulates ion transport across heterogeneous solid phases, offering a basis for designing next-generation hybrid solid electrolytes.

Novel oxalamide ligands with precisely tuned electronic properties enabled copper-catalyzed coupling reactions of (hetero)aryl chlorides with a broad range of N-heterocycles. Under the optimized conditions, more than 21 structurally diverse N-heterocycles proved to be applicable, among which nine were identified for the first time as suitable coupling partners in metal-catalyzed N-arylation reactions. The pK(a) values of the N-heterocycles were found to be reliable indicators for selecting optimal reaction conditions.

Cell-surface glycans exhibit extensive microheterogeneity, yet their site-specific dynamic behavior remains largely uncharacterized due to the lack of effective analytical methods. Here, we report a chemical enrichment strategy for profiling the temporal dynamics of intact cell-surface sialylated N-glycopeptides at site-specific and single-glycoform resolution. This method integrates metabolic labeling of sialylated glycans with azide reporters, copper-free strain-promoted azide-alkyne cycloaddition (SPAAC) using a photocleavable biotin probe for glycan labeling in living cells, and affinity enrichment of intact glycopeptides. Coupling this strategy with pulse-chase analysis enables quantitative tracking of glycan turnover across multiple structural levels, including glycoproteins, glycosylation sites, glycans, and site-specific glycoforms. The results reveal distinct turnover kinetics among glycoforms at the same site and show that glycan-level dynamics can differ substantially from protein-level stability. This work provides a robust analytical platform for investigating cell-surface glycan dynamics with high structural resolution.