Synthesis of chiral α-fluorovinyl β-aryl/heteroaryl/alkyl amino alcohols was achieved via intermediate 4-(α-fluorovinyl) 2,2-dimethyloxazolidines with stereochemically defined preexisting stereogenic centers, derived from (S)- or (R)-serine. Previously unknown 4-fluorovinyl 2,2-dimethyloxazolidines with a fluorine atom placed alpha to the oxazolidine were prepared via Julia olefination of tert-butyl (S)-4-{(S)-[benzo[d]thiazol-2-ylsulfonyl]fluoromethyl}-2,2-dimethyloxazolidine-3-carboxylate and its (R,R) enantiomer, with a series of aldehydes. By choice of conditions, olefinations could be tuned towards Z- or E-selectivity. E/Z olefin mixtures with electron-rich aryl and heteroaryl substituents were isomerized exclusively or predominantly to the Z-isomer. N-Boc protected β-aryl/alkyl substituted α-fluorovinyl amino alcohols were obtained by oxazolidine hydrolysis. To demonstrate utility for synthesis of amino acids, (R,Z)- and (S,Z)-p-methoxyphenyl- and the (S,E)-p-cyanophenyl-substituted alkenes were subjected to oxidation, which was very challenging. The use of cat. TEMPO/cat. NaOCl/NaClO gave the N-Boc protected fluorovinyl amino acids that were converted to their methyl esters. Enantioselective HPLC of the (S)- and (R)-p-methoxyphenyl-substituted products formed at each step of the synthetic sequence indicated that high enantiomeric purity was retained through the entire synthesis. Crystal structures of two fluorovinyl oxazolidines and one amino alcohol provided insight into the solid-state conformations. NMR and computational analyses were used to obtain insight into plausible solution conformations.

Glycosidases are key enzymes involved in carbohydrate metabolism. Members of the GH3 family have emerged as therapeutic targets due to their roles in natural product biosynthesis and disease. Transition-state analogues represent a powerful strategy for glycosidase inhibition, and exoglycals (C-glycosylidenes) have gained interest as conformational mimics of glycosidic bond hydrolysis. Herein, we report the synthesis of novel exoglycals bearing diverse substituents, including terminal alkynes and thymidyl residues, via a modified Julia-olefination strategy from sugar-derived lactones and substituted sulfones. Selected alkyne-containing exoglycals were further functionalized through cycloaddition with azidothymidine. Inhibition studies against EryBI, a GH3 glycosyl hydrolase, were performed. Kinetic analysis revealed diverse inhibitory mechanisms among the exoglycals, displaying competitive inhibition, with K values spanning micromolar to millimolar affinities. To contextualize the inhibitory potential of exoglycals, we evaluated three clinically relevant macrolide antibiotics-erythromycin, clarithromycin, and azithromycin. Intriguingly, these macrolides exhibited competitive or uncompetitive inhibition, contrasting with the consistent competitive behavior of exoglycals. This comparative analysis highlights the scaffold-dependent selectivity of GH3 inhibition. Our results demonstrate exoglycals as tunable scaffolds for glycosidase inhibition of GH3 glycosidases and provide mechanistic distinctions between carbohydrate mimics and macrolide antibiotics. These insights could guide the development of next-generation glycosidase inhibitors with improved specificity.

Since the 1980s, the patch-clamp technique has revealed subconductance states (substates) in natural ion channels in addition to the traditional closed and fully open states. While subconductance states offer critical insights into the structure and function of ion channels, the structural basis underlying this behavior remains unclear. Artificial ion channels can serve as simplified molecular models to establish structure-function relationships; however, replicating subconductance behavior is extremely challenging. Here, we present a concept for a conformationally self-tuning macrocyclic skeleton designed to observe and modulate subconductance states in artificial channels. This concept was experimentally validated using oxacalix[2]arene[2]triazine-based molecular funnels.

Extremely high base concentrations (c) in ultra-alkaline liquids, also known as hydroflux, alter the thermodynamic and structural properties of water. Mixtures of water and alkali (AOH, A = Na, K) with molar base ratios of q(A) = n(HO):n(AOH) ≤ 2:1 (c ≥ 25 mol L) show an overproportionally reduced vapor pressure compared to more diluted systems. The vapor pressure of a melt with q(A) = 0.8 (c = 70 mol L) at 200°C is negligible. Ab initio molecular dynamics simulations revealed substantial structural reorganization of the hydrogen bonding network in the equimolar mixture of KOH and water. Distinctive molecular features included altered coordination geometries, shortened hydrogen bonds, and frequent proton transfer events, including Grotthuss diffusion, indicative of an altered hydrogen-bond network and increased proton mobility. Cluster population analysis shows that a significant number of HO anions are present, which exhibit a near symmetrical hydrogen bond with O···H distances <1.28 Å. The hydroflux can be seen as an intermediate between an alkaline solution and a molten salt {K·H·2OH-}, in which the water has a vanishing chemical activity.

A novel J-aggregates configuration, termed π-π-coupled J-aggregates, was successfully constructed based on low-molecular-weight hemicyanine dyes (HCY-3). Unlike classical J-aggregates, the π-π-coupled J-aggregates are formed through synergistic π-π stacking and hydrogen bonding interactions between monomeric molecules, The rigidified- molecular planar architecture not only avoids fluorescence quenching of the photosensitizer but also significantly broadens the bathochromic absorption band owing to enhanced conjugation effects while preserving photodynamic activity. As a result, a broad bathochromic absorption from 600 nm to an absorption tail over 1100 nm was achieved, allowing the photosensitizer to be compatible with a variety of laser sources. The enhanced-receptor conjugation significantly boosts singlet oxygen generation efficiency while reinforcing π-π interactions, endowing the J-aggregates with exceptional thermal stability, chemical stability, and photothermal generation capability. Under 980 nm laser excitation, the π-π-coupled J-aggregations based on HCY-3 J-NPs exhibited excellent ROS generation capacity and NIR-II fluorescence emission, successfully achieving multimodal photothermal/photodynamic antitumor therapy guided by NIR-II FL imaging. Such π-π-coupled J-aggregates may represent a new route for the design of NIR-II photosensitizers.

Carbazolide complexes of lanthanum and terbium with cyclooctatetraenediide (COT) and THF coligands of the type [(Cbz)LnCOT(thf)] (n = 2 for La, 1 for Tb) were synthesized by salt metathesis reactions. The THF molecules were found to be labile, and drying under vacuum led to their partial removal with concomitant formation of the dinuclear complexes [(Cbz)Ln(COT)(thf)]. The luminescence of both lanthanum and terbium complexes was investigated, and at cryogenic temperatures, strongly temperature-dependent phosphorescence was observed. The terbium complexes show the expected element-characteristic emission with narrow lines between 480 and 700 nm upon excitation at 370 nm. Beyond that, broad emission was induced selectively by excitation at lower energy. Related phosphorescence was found for the lanthanum complex, which implies intra- or inter-ligand excitation as source for the latter. This interpretation was corroborated by TD-DFT computations.

The identification of drug targets remains one of the most critical challenges in pharmaceutical research. The rapid progress of artificial intelligence (AI) is significantly advancing this landscape by enabling more efficient and accurate drug-target interaction prediction. AI-driven approaches can integrate and analyze massive biomedical datasets, elucidating complex signaling networks and providing systematic insights into drug mechanisms of action. These developments have greatly accelerated virtual screening, binding affinity estimation, and target identification. However, despite these advancements, key challenges persist, such as ensuring the precision of predictions and overcoming the barriers to integrating AI tools with drug target discovery. This review provides a comprehensive overview of recent public databases, advanced computational methods, and user-friendly AI tools, highlighting both their potential and challenges. It also offers practical guidance for researchers without computational expertise, illustrating how these technologies can be effectively incorporated into current research workflows to advance drug target discovery and ultimately accelerate the development of novel therapeutic drugs.

2D materials have attracted a lot of interest since the invention of graphene because of their remarkable qualities and adaptability. The distinct architectures and complementary qualities of MOFs (metal-organic frameworks) and MXenes offer intriguing prospects in various sectors. Derived from MAX phases, MXenes have hydrophilic surfaces, and excellent electrical conductivity. MOFs, on the other hand, provide large surface area, adjustable porosity, and diverse chemical functions. Nevertheless, there are drawbacks associated with both materials. MXenes are prone to oxidation and self-stacking, whereas MOFs have limited structural stability and poor electrical conductivity. The development of MXene@MOF composites provides a synergistic solution, combining the advantages of both materials while reducing their individual drawbacks. In this review, we highlight the most recent advances in MXene@MOF composites and provide a focused discussion on their unique structural features, emerging synthesis trends, and rapidly expanding applications. These elements distinguish this work from earlier reviews. This review systematically explores the structures and synthesis methods of these materials, including solvothermal, hydrothermal, and in-situ growth techniques, and examines their wide range of applications. Superior electron transport, high surface area, and improved structural stability lead to enhanced performance of MXene@MOF composites in supercapacitors, water splitting, photocatalysis, and sensing.

To develop fast-charging lithium-ion batteries (LIBs), optimizing insertion-type anode structure is crucial for achieving fast lithium-ion diffusion and high electronic conductivity. Here, we combine insertion-type TiO with high-capacity FeCoS to construct a TiO/FeCoS heterojunction, which enhances electron/ion transport, lowers the ion diffusion energy barrier, and thereby improves quick-charging performance. The resulting anode exhibits a high reversible capacity of 627.7 mAh g at 0.1 A g, 2.3 times that of TiO. Notably, it gives a remarkable capacity of 241.7 mAh g at 10 A g and maintains excellent stability over 10,000 cycles with an ultralow capacity decay of just 0.002% per cycle. Experiments and theoretical calculations confirm the superior performance originates from enhanced Li ions adsorption and reduced diffusion barrier at the heterointerface, which accelerates Li insertion/extraction kinetics. This work provides an effective pathway to accelerate electrochemical kinetics and enable fast-charging LIBs.

DNA ligation is a fundamental reaction used in a variety of applications, typically performed by T4 DNA ligase. For certain applications, such as DNA data storage, DNA-ligating DNAzymes offer a more stable and cost-effective alternative to protein enzymes. The E47 DNAzyme is among the most efficient DNA-ligating DNAzymes reported, but it still lacks sufficient activity for widespread adoption and requires a highly unstable phosphoimidazole-activated DNA substrate to function. In this study, we performed in vitro selection using a pre-structured library based on E47 and identified sequences with more than a twofold increase in ligation activity, representing the fastest DNA-ligating DNAzymes reported to date. We also screened alternative imidazolide compounds for substrate activation and found that phosphobenzimidazole-activated DNA substrates are significantly more stable, remaining intact for at least 24 h at room temperature. These advances improve the practicality of DNAzymes for ligation-based applications and broaden their potential use in DNA data storage.

In the domain of bottom-up approach, regioselective fusion of aromatic moiety onto an arene templet remains scarcely explored, yet represents a crucial tool for the rapid generation of polycyclic aromatic hydrocarbons (PAHs). An unprecedented bottom-up strategy for the rapid construction of PAHs is developed by employing arene-derived ketones and carbon-rich 1,3-diynes. Many of these synthesized PAHs have tilted π-electronic structure, unique edges and topologies. A range of arene-derived ketones participated in this annulative-π-extension-cyclization cascade under first-row Co(III)-catalysis. Electronic nature of the 1,3-diynes guided the final mode of cyclization leading to the formal fusing of one fluorene moiety via 5-exo-dig cyclization or phenanthrene nucleus through 6-endo-dig cyclization. Intermediate ethynyl-PAHs were also isolated in case of relatively electron-deficient diynes. The contorted π-planes of the synthesized PAHs were elucidated by single-crystal X-ray analysis. Detailed DFT studies reinforce the proposed mechanistic pathway, validating the formation of the major regioisomer of PAHs. Furthermore, less aromatic character of fluorene moiety over phenanthrene nucleus is supported by the NICS(1) and ACID calculations.

With the continuous scaling and integration of semiconductor devices, the demand for advanced chemical-mechanical polishing (CMP) has increased significantly. Consequently, the limitations of conventional abrasives have become increasingly evident, prompting a growing need for next-generation slurries with improved material removal rates, surface roughness, defectivity, and selectivity. This review investigates the physicochemical properties of both ceria-based and nonceria-based nanoparticle abrasives and critically examines recent advances in their application to SiO CMP. Emphasis is placed on understanding how these materials contribute to performance enhancement through chemical interactions, mechanical properties, and structural design. Our findings suggest that overcoming the limitations of the existing slurry systems may require a paradigm shift from relying on single-component abrasives to engineering composite systems with complementary functionalities. Such integrated abrasive design strategies present a practical route toward more reliable and effective CMP solutions for future semiconductor fabrication.

Two hydrogen-bonding monomers containing tetraethylene glycol (TEG) chains have been synthesized and characterized. The monomers are based on a bicyclic scaffold appended with either 4H-bonding benzyl-substituted ureidopyrimidinone motifs or 2H-bonding unsubstituted pyrrole-fused ureidopyrimidinone motifs, with the TEG chains introduced with the aim of developing amphiphilic monomers soluble in nonpolar and polar organic solvents in order to extend the utility of H-bonding in supramolecular chemistry. In CDCl, both monomers formed cyclic tetramers. The monomer containing 2H-bonding motifs was found to form significantly less-stable aggregates than its previously reported alkylated analogue, most likely due to interference from the TEG chains. Despite the weaker aggregation, the 2H-bonded tetramers were able to stack into tubular polymers through orthogonal H-bonding in less polar solvent (toluene) or when a suitable guest (C) was introduced. Comparison of the TEGylated monomers with previously reported alkylated analogues showed that the introduction of TEG chains resulted in increased solubility in a wide range of solvents. By using one of the TEGylated monomers, nonpolar C could be solubilized in polar solvent acetonitrile by forming an inclusion complex. This complex was used as a homogeneous catalyst for photochemical oxidation of sulfides to sulfoxides in acetonitrile.

Clean synthetic strategies that embrace the inherent structural features of renewable building blocks to obtain biologically active compounds hold great potential to improve the economic viability of emerging biorefineries. Importantly, such an approach is highly beneficial for the sustainable manufacturing of pharmaceutically relevant molecules. Here, we demonstrate a one-step protocol toward biologically active isochromans through the Oxa-Pictet cyclization involving both aromatic aldehydes, including vanillin, and aliphatic aldehydes in combination with lignin-derivable homovanillyl alcohol (1), a prominent aromatic platform chemical obtainable via diol-assisted fractionation. Employing tunable deep eutectic solvents as benign reaction media allows for modulating reactivity under mild reaction conditions, and opens access to a library of isochromans in a single step. Several compounds exhibit promising properties, including PPI inhibition, anticancer, and antibacterial activities, highlighting the benefits of this synthetic strategy and its potential for drug discovery.

Thiocarboxylate paddlewheels (PWs) [MTr(SOCR)L] (M = Pt, Pd; Tr = first-row transition metal; L = Tr-coordinated axial ligand) form a variety of dimeric structures via M···M' and M···S' contacts. We found that [PtVO(SOCPh)] (1), a molecular spin qubit, yields three crystalline toluene (tol) solvates, namely 1·0.875tol and two polymorphic 1·0.5tol phases. The crystals contain either staggered quasi-coaxial dimers with short Pt···Pt' distances (3.17-3.23 Å) or heavily bent noncoaxial molecular pairs supported by Pt···S' contacts (3.34-3.38 Å). By contrast, in the known solvatomorphs 1·CHCl and 1·0.5hex (hex = n-hexane), two collinear molecules compose a "square" dimer via a pair of reciprocating Pt···S' contacts (3.13-3.16 Å). According to gas-phase DFT calculations (PBE0/def2-TZVPP/D3BJ), dimerization is energetically favored by 15-20 kcal mol and is guided by a shallow potential energy surface, with staggered dimers as ground configurations but eclipsed and square dimers well within energetic reach. Inspection of the local energy minima also disclosed a previously unrecognized eclipsed arrangement with ∼45° twisting of both PWs relative to the metal plane, whose existence was confirmed by statistical analysis of PW structures in the Cambridge Structural Database. Our results led to a new classification scheme for these PW dimers relevant to molecular magnetism and quantum technologies.

The functionalization of solid surfaces with responsive macrocyclic compounds is a key strategy for developing advanced functional materials, with applications in molecular sensing, catalysis, and nanoscale electronics. Here, we report the self-assembly and lateral cobalt coordination, on an Au(111) surface and under ultra-high vacuum conditions, of a fivefold symmetric cyanostar macrocycle, a class of anion recognition molecules. This represents the first example of a close-packed regular assembly of a pentagonal macrocycle at the solid-vacuum interface.

A new series of imido-vanadium(V) complexes bearing bidentate phenoxy-phosphine ligands was synthesized in high yields and fully characterized by NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. These complexes were systematically evaluated as efficient catalysts for ethylene polymerization. Among them, complex C1 exhibited exceptional activity, up to 446.5 × 10 g (mol)·h, along with excellent thermal stability (120°C), long catalytic lifetime (120 min), and broad solvent compatibility. The produced polyethylene samples spanned moderate to ultra-high molecular weights, with a maximum of 160.4 × 10 Da. Systematic structure-activity-polymer investigations revealed that both steric and electronic variations on ligand critically tune catalytic behavior and polymer properties, underscoring the effectiveness of phenoxy-phosphine framework and providing valuable insights for the rational design of high-performance polyolefin catalysts.

A series of rigid-flexible unsymmetrical bulky α-diimine palladium catalysts was employed for the gas-phase polymerization of ethylene, enabling the synthesis of hyperbranched ultrahigh molecular weight polyethylene (UHMWPE). Compared to conventional solution-phase polymerization, the gas-phase method significantly suppresses chain transfer while promoting chain walking, leading to a simultaneous increase in both molecular weight and branching density. Under optimized conditions, the resulting polyethylene exhibited high molecular weight (up to 2053 kg/mol) and branching densities as high as 107 branches per 1000 carbon atoms. Structural characterization confirmed the presence of long-chain branches and branch-on-branch architectures, indicative of a hyperbranched topology. The unsymmetrical palladium catalysts produced polyethylene with higher molecular weight and branching density than the benchmark catalysts, by combining suppressed chain transfer with high chain-walking ability. This work demonstrates the potential of gas-phase polymerization as a solvent-free, environmentally benign route to advanced polyolefin materials with tailored architectures.

This Perspective describes an apparent transition in the design and function of synthetic receptors for proteins. It is shown that the original receptor design, geared toward protein recognition, lends itself also to receptor self-assembly and concomitant protein assembly. While evidence for this effect has lain somewhat dormant for two decades, numerous recent examples raise interesting possibilities for innovation in protein binding, encapsulation, and crystal engineering. In a bid to inspire future research and collaboration, I speculate on new receptor designs. Considering current developments with nanocarbon hosts, anionic variants might facilitate protein assembly and the bottom-up fabrication of hybrid materials.

Measuring the catalytic activity of specific sizes of polymers with active catalysts in solution is typically challenging, due to limited instrument detection sensitivity and/or dynamic range. Here, a fluorescence correlation spectroscopy (FCS) method is developed to determine the catalytic activity of living polymers of a specific apparent size in solution. Deviation from a single-component FCS data fitting, as assessed by χ, is also introduced and developed as a "speciation index"-a method to evaluate and track changes in the relative amount of distinct polymer sizes with reaction progress. These methods are enabled by incorporating a selectively reactive fluorescent monomer into growing polydicyclopentadiene or polynorbornene during ring-opening metathesis polymerization (ROMP). Compared to polynorbornene, data showed that catalysts in aggregates of polyDCPD retained higher activity for longer-outcomes not directly inferable from simple diffusional-access predictions. The ability to assign catalytic activity to polymers of specific sizes, and then to determine how this activity evolves with reaction progress, support long-term goals in the development and measurement of nano-objects that possess size-dependent catalytic activity.

The highly homologous transcription factors STAT5a and STAT5b are overactivated in many human tumor types. We recently reported catechol bisphosphates as the first chemical entities that inhibit STAT5b with selectivity over STAT5a. Here, we apply conformational restriction strategies to increase the activity and selectivity of Stafib-2, the most potent STAT5b inhibitor reported to date. The best conformationally restricted Stafib-2 analogue 8b (dubbed Stafib-2-CR) displayed approximately threefold higher activity against STAT5b than Stafib-2, associated with higher selectivity over STAT5a. Its cell-permeable prodrug 17 (dubbed Pomstafib-2-CR) inhibits phosphorylation of STAT5b in cultured human leukemia cells with slightly higher activity and selectivity over STAT5a than Pomstafib-2, the prodrug corresponding to Stafib-2.