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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

Living crystallization-driven self-assembly (CDSA), employing a seeded growth method, has emerged as a pivotal strategy for achieving precise control of anisotropic nanoparticles over the dimensions and structure, which enables the fabrication of 1D cylinders and 2D platelets with low dispersity. This versatile and robust approach, characterized by linearly tunable dimensions and programmability of structural sequences, has been widely applied in the construction of nanoparticles exhibiting uniform size and controlled architecture. A critical aspect of this technique lies in heteroepitaxial crystallization, which transcends the chemical composition constraints of conventional homoepitaxy and enables the design of segmented structures with spatially distinct core components. Building upon this foundation, we elucidate the key aspects of living CDSA seed growth, with a particular emphasis on exploring the mechanism of governing heteroepitaxial growth from crystalline seeds with distinctly chemical compositions. Elucidating the intricate mechanisms of heteroepitaxial crystallization allows access to broaden the design possibilities for segmented nanoparticles with spatially defined core compositions and functionalities. Moreover, the new developing methods for facile synthesis of uniform particles with high solid concentrations are also reviewed, which are promising for the real applications of these advanced nanomaterials.

Configurationally stable chiral octaazaperopyrene dioxide (OAPPDO) derivatives were obtained by nucleophilic substitution of chiral BINOL and related fragments as bridging units onto the bay position. The addition of these phenolate derivatives has given rise to a new group of bright chiral fluorophores with remarkable thermal stability, which allowed the study of their chiroptical properties, in particular, their circular dichroism characteristics as well as circular polarized luminescence (CPL), albeit with a low dissymmetry factor (g) in the range of 2*10. The introduction of the BINOL bridging groups in the bay position led to equilibria between chiral conformers in solution, the interconversion of which has been studied by DFT modeling, with the two lowest energy species being directly observable in situ by NMR. Insight into the stability of these derivatives with respect to overall racemization has been obtained by DFT modeling which established an overall activation barrier for the process of above 170 kJ mol.

(RRR)-α-tocopherol reacts with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) at ambient conditions in a fast formal [6+2+2] addition reaction yielding four pairs of diastereomers, three of them containing novel heterocyclic ring systems. Structure elucidation required customized 3,5-C,4-N labelled PTAD to establish the connectivity of the PTAD units using J H-C, J C-C, and J C-N NMR correlations. Absolute stereochemistry was determined based on calculated CD spectra compared to experimental data. The reaction occurred also with related 6-chromanols and required a free phenolic hydroxy group. As one possibility, the addition of the first PTAD involves a hetero-Alder-ene reaction, followed by a Diels-Alder or alternative addition / cyclization of a second PTAD. Together with the derivatization of vitamin K and the known reactions with vitamins A and D, PTAD can thus derivatize all fat-soluble vitamins in a one pot reaction, offering potential new applications for their analysis in complex matrices.

Oligonucleotides capable of guiding adenosine deaminases acting on RNA (ADARs) to carry out therapeutic adenosine (A) to inosine (I) editing constitute a promising new class of nucleic acid therapeutics. However, our understanding of the impact of different chemical modifications at the various nucleotide positions in ADAR guide strands is limited. While ribose 2' modification is common in ADAR-directing guides, less is known about the impact of modification at the 4' position. Here we describe the synthesis of several 4'-Cα-methyl and 2'-O, 4'-Cα-dimethyl derivatives of adenosine, uridine, and cytidine and their incorporation into RNA. In addition, we show that these analogs maintain the base pairing selectivity of their parent nucleoside and modulate duplex thermal stability in an analog-dependent manner. High-resolution crystal structures of RNA duplexes bearing 4'-Cα-methyl A or U showed that these analogs adopt a C3'-endo sugar pucker and project 4' substituents into the minor groove. Finally, we find that 2'-O, 4'-Cα-dimethyluridine and 2'-O, 4'-Cα-dimethyladenosine strategically positioned in ADAR guide strands can increase the selectivity of the editing reaction for target sequences with adjacent off-target adenosines. This work advances our understanding of the ADAR reaction mechanism and informs the design of ADAR guide strands with improved selectivity.

Ketoleucine (α-ketoisocaproate) is a novel hyperpolarized substrate for noninvasive metabolic imaging, enabling rapid, high-sensitivity detection of branched-chain amino acid flux, a pathway that is aberrant in many diseases including cancer and Alzheimer's disease. Utilizing NMR Signal Amplification by Reversible Exchange (SABRE) with an 80:20 acetone:water solvent system, we achieved >11% polarization of [1-C]ketoleucine (corresponding to signal enhancement over 230,000-fold at 0.55 T) at 70 mM within 2 min, using parahydrogen as a cheap and fast source of hyperpolarization. A two-stage liquid-liquid extraction and gas stripping protocol removes excess excipients, yielding a biocompatible aqueous solution of [1-C]ketoleucine (79 ± 10 mM). When mixed with Saccharomyces cerevisiae (Baker's yeast), hyperpolarized [1-C]ketoleucine produced strong, long-lasting signals, where downstream metabolites are observed for >200 s, allowing first-order kinetic modeling of CO and bicarbonate. These cell experiments demonstrate both the biocompatibility and signal strength of SABRE-hyperpolarized KL, establishing KL as a versatile hyperpolarized agent and opening avenues for real-time investigation of metabolic dysregulation in cancer, neurodegenerative disorders, and beyond.

The reaction of ammonium pertechnetate, (NH)(TcO), with SO leads to crystals of (NH)[TcO(SO)] (monoclinic, P2/c, Z = 2, a = 775.67(5), b = 1339.55(8), c = 1233.32(8) pm, β = 100.566(2)°). The compound contains the dimeric [TcO(SO)] anion with the Tc atom connected by disulfate anions. It is astonishing that even under the oxidizing reaction conditions, reduction of the Tc(VII) starting material occurs. Contrastingly, an analogous reaction of (NH)(ReO) with SO gives the Re(VII) sulfate (NH)[ReO(SO)] (orthorhombic, Pca2, Z = 8, a = 1842.7(1), b = 847.03(5), c = 1663.8(1) pm). The compounds have been further studied by vibrational spectroscopy and quantum mechanical calculations.

Targeted protein degradation (TPD) using proteolysis-targeting chimeras (PROTACs) offers advantages over occupancy-based inhibitors but faces challenges, including ligand discovery and cellular permeability. To address these limitations, we developed Re2, a metallo-PROTAC integrating a covalent rhenium(I) complex warhead targeting SARS-CoV-2 main protease (Mpro) Cys145 with the cereblon E3 ligase ligand pomalidomide. Re2 induced effective intracellular Mpro degradation at 100 nM within 72 h, which is significantly below its parent complex's enzymatic inhibition concentration. In vitro and ex vivo studies confirmed covalent Mpro binding and ubiquitin-proteasome system-dependent degradation. Crucially, Re2 exhibited three- to fourfold higher cellular uptake and greater intracellular accumulation than its demetallated organic counterpart, demonstrating that metalation overcomes intrinsic PROTAC permeability barriers. This work establishes metallo-PROTACs, exploiting the tunable coordination chemistry of metal complexes for enhanced target engagement and cellular delivery, as a potent strategy for designing high-potent PROTACs.

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.