Synthesizing functionalized polyethylenes via ethylene coordination copolymerization with fundamental low-cost vinyl polar monomers provides a very attractive approach. However, it is also very challenging as the functional group (FG) to be introduced onto the polyolefin chain is directly derived from the corresponding vinyl polar monomers (CH2 = CH-FG), which often cause catalyst poisoning due to the FG coordination to active metal center and beta-X elimination during catalysis, etc. It is especially true for the synthesis of cyano-functionalized polyethylenes (PEs) via ethylene/acrylonitrile copolymerization, which can only rely on Pd catalysis with low activity. Here we present an approach utilizing binuclear Ni catalysis for ethylene/acrylamide copolymerization and the synthesis of cyano-functionalized PEs (>99%) with great activity up to 4.1 x 10(6) g/(mol cath). Extensive polymer characterizations (NMR, GPC, model experiments, etc) confirm significant chain transfer and the conversion of amide to nitrile during catalysis. Mechanistic investigations, including comprehensive control experiments, deuterium labeling and computational studies, support an isomerization-mediated chain transfer polymerization (ICTP) mechanistic pathway, which include tandem acrylamide enchainment, amido group conversion into CN group, and active catalyst regeneration by Et2AlCl. Catalyst poisoning could be largely circumvented by this catalyst system.

The alpha-effect refers to the dramatically enhanced reactivity of alpha-nucleophiles bearing a heteroatom with an adjacent lone-pair (R-Y-X:-) compared to normal nucleophiles (R-X:-), as predicted by Br & oslash;nsted-type correlation. Despite extensive research, the underlying mechanisms of this phenomenon remain debated, and previous studies have predominantly focused on O-, N-, and S-based nucleophiles, leaving carbanions-key intermediates in organic synthesis-comparatively underexplored. Here, we present an in-depth computational investigation into the intriguing influence of alpha-fluorine substitution on carbanion nucleophilicity. Despite fluorine's strong electron-withdrawing capability, our results reveal that alpha-fluorocarbanions could exhibit the alpha-effect when they satisfy Hamlin's two criteria originally proposed for heteroatom-based anionic alpha-nucleophiles. This study extends the scope of the alpha-effect from heteroatom-based nucleophiles to carbanionic nucleophiles, offering new insights into this fundamental chemical phenomenon.

Design and synthesis of electrochemical active molecules with high specific capacity attracted much research attention in the field of organic electrode materials for rechargeable betteries. Two bipolar molecules BPZ-AQ and 2BPZ-AQ which were composed of p-type dihydrophenazine and n-type anthraquinone moieties were synthesized via Buchwald-Hartwig coupling reaction. BPZ-AQ and 2BPZ-AQ could deliver high specific capacity of 230 and 223 mAh center dot g(-1), respectively. Their bipolar-type property was investigated by absorption spectrum and cyclic voltammetry characterization, confirming the electrochemical activity of dihydrophenazine and anthraquinone moieties in the bipolar molecules. 2BPZ-AQ can present a high initial capacity of 210 mAh center dot g(-1) at 1 C corresponding to 94% of its theoretical capacity, good capacity retention (60%) after 200 cycles, and excellent rate performance.

5,10-Dimethylphenazine (DMP) is a recently reported high-performance organic electrode material, however, its high solubility in electrolyte solution is responsible for the capacity decay during cycling. Poly(2-vinyl-5,10-dimethylphenazine) (PVDMP), containing DMP as active groups, shows limited solubility in electrolytes, whereas the impact of its molecular weight on the electrochemical properties has not been well investigated. Here, PVDMPs with two molecular weights, PVDMP-2K (M-w=2300 g center dot mol(-1)) and PVDMP-12K (M-w=12000 g center dot mol(-1)) were prepared. Cyclic voltammetry (CV) characterization shows that the peak current (ip) increased linearly with the concentration of PVDMP at low concentrations, while at high concentrations, there was a poor linear relationship between ip and Mw. This result demonstrated that the molecular weight of PVDMP affected its electrochemical behaviors. From the morphology investigation, it can be seen that PVDMP presented spherical aggregates with different diameters in solution and the diameter is increased with the molecular weight of PVDMP. Therefore, this spherical aggregate could influence the diffusion efficiency of PVDMP during the electrochemical reaction and the utilization of the active groups, and thus demonstrated different electrochemical behavior.

Chiral organophosphorus compounds have a wide range of application in the fields of medicine, pesticides, and functional materials, and also serve as versatile ligands or organocatalysts in asymmetric catalysis. Therefore, their asymmetric synthesis has attracted an increasing attention from chemists and has become one hot research topic in recent years. Asymmetric P-C or P-N bond formation by using organophosphorus compounds bearing P-H bond and various electrophilic partners serves as a straightforward and powerful strategy for constructing chiral organophosphorus compounds. The recent progress in asymmetric synthesis of chiral organophosphorus compounds catalyzed by chiral copper complexes or copper/organocatalyst co-catalytic systems is summarized. P-Chiral or/and backbone chiral organophosphorus compounds were obtained in these reactions. This paper is divided into two sections based on whether the valence state of copper is changed or not during the reaction process. Aside from the substrate scopes, the mechanisms and potential applications of some representative methodologies are also included.

The gemini cationic surfactant is a type of surfactant that simultaneously connects at least two hydrophobic hydrocarbon chains and two polar head groups through one intermediate group. Multiple hydrophobic chain segments and hydrophilic groups act concurrently in the system, enabling more effective reduction of the surface tension within the system. However, within the research realm of alternatives to fluorinated surfactants, the potential of the gemini cationic surfactant structure as a substitute has received relatively little attention. In this study, we synthesized tertiary amines using CF3OCF(CF3)CF2OCF(CF3)- (C72), CF3(OCF2)(3)- (OC3), CF3(OCF2)(4)- (OC4) and C5F11- (C6) methyl esters in methanol solvent at room temperature. Subsequently, a series of gemini cationic surfactants were obtained through the quaternization of the tertiary amine with one benzylbromide and three dibromide compounds in acetonitrile solvent. The reaction conditions for most samples were mild. After purification, the purity of the samples could nearly reach 95%, which rendered the surface activity characterization results more accurate and persuasive. The sample named C72(Et)-o-phenyl-C72, which features diethyl substitution, requires the optimization of reaction conditions. Subsequent purification through column chromatography is necessary to obtain products of high purity. 1% (w), 0.1% (w), 0.01% (w) and 0.001% (w) solutions were prepared for each compound, and the surface tension was measured by the Wilhelmy plate method. The properties of the samples were compared, and the rule between the properties of fluorine-containing gemini cationic surfactants and the degree of incorporation of oxygen atoms on the hydrophobic chain, as well as their different isomers, was preliminarily explored. The results suggest that the characterization results of OC3 and OC4 series samples, of which hydrophobic chain segment featured repetitive-OCF2O- units, are the most favorable, and the sample properties are minimally affected by the structure. The sample surface activity of C72 series samples, whose hydrophobic chain segment contains only two oxygen atoms, are relatively low, while the sample characterization results of C-6 samples, which has no oxygen atoms, are the least outstanding. The results manifest the uniqueness and feasibility of the fluoroether chain segment gemini cationic surfactants, and the structure has potential to serve as a substitute for long-chain fluorocarbon surfactants.

Covalent organic frameworks (COFs) represent a fascinating class of crystalline porous polymers constructed from organic building blocks linked by covalent bonds. Benefiting from their high crystallinity, large surface area, and ease of functionalization, COFs have demonstrated significant potential across various fields, including gas adsorption, luminescence, sensing, catalysis, energy storage, nanomedicine, etc. In the first decade of COF development, only those with homogeneous porosity have been constructed, and thus, their topological structures are quite limited. An exciting progress in the field of COFs is the emergence of two-dimensional (2D) COFs with hierarchical porosity, known as heteropore COFs, which have garnered considerable attention in recent years. Heteropore COFs are deliberately designed to integrate different types of pores into a single framework, resulting in heterogeneous porosity that imparts captivating properties and functions. Compared to their homopore counterparts, heteropore COFs offer a compelling platform for creating hierarchically structured porous materials, thanks to their distinctive multicompartment architectures and different pore environments. Since we achieved the construction of the first heteropore COF featuring both micropores and mesopores in 2014, substantial advancements have been achieved in the realm of heteropre COFs over the past decade, considerably increasing the topological diversity of 2D COFs. In this Account, we summarize our contributions to the development of 2D heteropore COFs. First, we review representative design strategies for the construction of 2D heteropore COFs, including the angle-specific-vertex, heterostructural-mixed-linker, multiple-linking-site, and desymmetrization-design strategies and their combinations as well as the dynamic covalent chemistry-mediated linker exchange strategy. Based on these strategies, heteroporous frameworks with two, three, and four different kinds of pores and different types of linkages have been successfully fabricated. Next, we discuss the properties and applications of heteropore COFs, including those shared with their homopore counterparts and unique ones originating from their hierarchical porous structures. Our research has shown that heteropore COFs have inherited the common features from their homopore counterparts and exhibited application potentials in gas adsorption, chemical sensing, environmental remediation, etc. More importantly, the multicompartment architecture and heterogeneous pore environment of heteropore COFs offer distinct benefits, for which exclusive applications and unique properties of heteropore COFs distinct from those of homopore COFs have been demonstrated. Finally, we highlight the current challenges and future directions of heteropore COFs, with an emphasis on the development of structural design and synthetic methodologies, precise structural characterization, and the exploration of unique properties and advanced applications. We believe that this Account will offer valuable insights into the design and synthesis of COFs with heteroporous structures, thereby accelerating their applications across a wide range of interdisciplinary research areas.

Photocatalytic carbon dioxide (CO2) reduction has emerged as a promising strategy for achieving carbon neutrality under mild reaction conditions. While methane (CH4) is widely regarded as a valuable target product in CO2 reduction studies, the reliability of such measurements can be compromised by unintended CH4 generation from solvent or sacrificial reagent decomposition during photoreactions. Herein, we systematically evaluate the stability of seven common solvents and five sacrificial reagents under visible-light irradiation (lambda >420 nm) in CO2-, air-, and N-2-saturated atmosphere, employing three distinct photosensitizers. Notably, acetone, dimethyl sulfoxide (DMSO), and triethylamine (TEA) were identified as high-risk reagents prone to photodecomposition, generating substantial CH4 yields of up to 2770 mu mol & sdot; h(-1) & sdot; L-1. Isotopic labeling experiments conclusively demonstrated that the source of CH4 originated from the solvents or sacrificial reagents rather than CO2. These findings highlight critical pitfalls in experimental design for photocatalytic CO2 reduction and emphasize the necessity of rigorous reagent screening to avoid artifactual methane production.

Benzene-forming cyclotrimerization reactions are capable of constructing cyclic structures via continuous transformation of three identical functional groups, and have applications in various fields such as natural product synthesis, polymer chemistry, supramolecular chemistry, and material science. In this review, the recent advances in cyclotrimerization reactions forming a central benzene ring are systematically summarized according to the different reaction types of functional groups. In each typical example, the reaction conditions, mechanism, possible side reactions, and applications are discussed. A future perspective on benzene-forming cyclotrimerization reactions is also presented.

Determining hydrogen positions in metal hydride clusters remains a formidable challenge, which relies heavily on unaffordable neutron diffraction. While machine learning has shown promise, only one deep learning-based method has been proposed so far, which relies heavily on neutron diffraction data for training, limiting its general applicability. In this work, we present an innovative strategy-SSW-NN (stochastic surface walking with neural network)-a robust, non-neutron diffraction-dependent technique that accurately predicts hydrogen positions. Validated against neutron diffraction data for copper hydride clusters, SSW-NN proved effective for clusters where only X-ray diffraction data or DFT predictions are available. It offers superior accuracy, efficiency, and versatility across different metal hydrides, including silver and alloy hydride systems, currently without any neutron diffraction references. This approach not only establishes a new research paradigm for metal hydride clusters but also provides a universal solution for hydrogen localization in other research fields constrained by neutron sources.

Five-membered ring motifs widely exist in many natural products, pharmaceuticals and organic materials, and are also important intermediates in organic synthesis and core structures for drug development. Therefore, highly efficient approaches for the synthesis of five-membered cyclic compounds are in high demand. [4+1] cycloaddition of readily available conjugated diene provides an efficient and straightforward strategy to construct five-membered carbo- and heterocyclic compounds in an atom-economic manner, and have therefore attracted more attention from the synthetic community. In recent years, duo the significant advances in transition-metal catalysis and precursors of one-atom synthons, [4+1] cycloadditions, which convert simple and readily accessible substrates into complex and diverse five-membered ring molecules, are rapidly growing and a series of excellent achievements have been reported. This review presents the progress in [4+1] cycloaddition reactions of conjugated diene with various one-atom synthons involving carbon monoxide (CO), carbenes, silylenes, germylenes and nitrenes. The reactions and their mechanisms are discussed according to the types of one-atom synthons. Furthermore, the challenges and future development trends in this field are also prospected.

The halogen effects, specifically the replacement of chlorine with fluorine, on the shift in regioselectivity from 1,4- to 1,2-addition in the nucleophilic haloalkylation of alpha,beta-enones have been investigated using density functional theory (DFT) calculations. Computational analysis revealed that the difluorocarbanion PhSO2CF2-, being a hard nucleophile with lower energy of the highest occupied molecular orbital (HOMO), selectively undergoes 1,2-addition of chalcone, primarily dominated by Coulombic interactions. In contrast, the nucleophilic 1,4-addition of chalcone by a soft dichlorocarbanion PhSO2CCl2- is controlled by frontier molecular orbital interactions. This work provides a deep understanding of the regioselective control in nucleophilic haloalkylation reactions.

This paper aims at developing a highly enantioselective ruthenium-catalyzed asymmetric hydrogenation of enamine ester to synthesize the chiral intermediate of sitagliptin. Through a comprehensive investigation of ruthenium catalyst precursors, chiral ligands, acids and ammonium salts as additives, temperature, pressure, and solvent, (R)-3-amino-4-(2,4,5- trifluorophenyl) isopropyl butyrate, the key intermediate of sitagliptin, was obtained in 97% yield and 99% ee by asymmetric hydrogenation from beta-2,4,5-trifluorophenyl- beta-enamine ester under the action of Ru-BIBOP catalyst, with p-toluenesulfonic acid and ammonium p-toluenesulfonate as additives, and dichloromethane/methanol as solvent, under 5 MPa of hydrogen pressure and 60 degrees C for 22 h. The use of Ru-BIBOP catalyst plays a key role in achieving high enantioselectivity for this transformation.

Divergent synthesis of valuable molecules through common starting materials and metal catalysis represents a longstanding challenge and a significant research goal. We here describe chemodivergent, highly enantio- and regioselective nickel-catalyzed reductive and dehydrogenative coupling reactions of alkynes, aldehydes, and silanes. A single chiral Ni-based catalyst is leveraged to directly prepare three distinct enantioenriched products (silyl-protected trisubstituted chiral allylic alcohols, oxasilacyclopentenes, and silicon-stereogenic oxasilacyclopentenes) in a single chemical operation. The use of a bulky C-2-symmetric N-heterocyclic carbene (NHC) ligand for nickel catalyst is the key to enable simultaneous exceptional control of stereo- and regioselectivity (up to 99% enantiomeric excess (ee), >99:1 regiomeric ratio (rr), >99:1 E/Z) and high efficiency (up to 99% yield). Computational studies elucidate the origin of chemodivergency and reveal the critical role of NHC in the enantioselectivity- and rate-determining oxidative cyclization step via an eta(2)-aldehyde eta(2)-alkyne Ni five-centered transition state. We expected that the enantioselective eta(2)-activation mode be widely applicable in other Ni-catalyzed carbonyl couplings. (c) 2024 Science China Press. Published by Elsevier B.V. and Science China Press. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Cyclin-dependent kinases 12 and 13 (CDK12/13) have emerged as promising therapeutic targets for castration-resistant prostate cancer (CRPC) and other human cancers. Despite the development of several CDK12/13 inhibitors, challenges remain in achieving an optimal balance of potency, selectivity and pharmacokinetic properties. Here, we report the discovery of YJZ5118, a novel, potent and highly selective covalent inhibitor of CDK12/13 with reasonable pharmacokinetic profiles. YJZ5118 effectively inhibited CDK12 and CDK13 with IC50 values of 39.5 and 26.4 nM, respectively, while demonstrating high selectivity over other CDKs. Mass spectrometry analysis, cocrystal structure determination, and pulldown-proteomic experiments confirmed the compound's covalent binding mode with CDK12/13. Functionally, YJZ5118 efficiently suppressed the transcription of DNA damage response genes, induced DNA damage, and triggered apoptosis. Moreover, the compound significantly inhibited the proliferation of multiple tumor cell lines, particularly prostate cancer cells. Notably, YJZ5118 exhibited synergistic effects with Akt inhibitors both in vitro and in vivo.

BACKGROUND:Heart failure (HF), which is the terminal stage of many cardiovascular diseases, is associated with low survival rates and a severe financial burden. The mechanisms, especially the molecular mechanism combined with new theories, underlying the pathogenesis of HF remain elusive. We demonstrate that phosphorylation-regulated dynamic liquid-liquid phase separation of HIP-55 (hematopoietic progenitor kinase 1-interacting protein of 55 kDa) protects against HF.METHODS:Fluorescence recovery after photobleaching assay, differential interference contrast analysis, pull-down assay, immunofluorescence, and immunohistochemical analysis were used to investigate the liquid-liquid phase separation capacity of HIP-55 and its dynamic regulation in vivo and in vitro. Mice with genetic deletion of HIP-55 and mice with cardiac-specific overexpression of HIP-55 were used to examine the role of HIP-55 on beta-adrenergic receptor hyperactivation-induced HF. Mutation analysis and mice with specific phospho-resistant site mutagenesis were used to identify the role of phosphorylation-regulated dynamic liquid-liquid phase separation of HIP-55 in HF.RESULTS:Genetic deletion of HIP-55 aggravated HF, whereas cardiac-specific overexpression of HIP-55 significantly alleviated HF in vivo. HIP-55 possesses a strong capacity for phase separation. Phase separation of HIP-55 is dynamically regulated by AKT-mediated phosphorylation at S269 and T291 sites, failure of which leads to impairment of HIP-55 dynamic phase separation by formation of abnormal aggregation. Prolonged sympathetic hyperactivation stress induced decreased phosphorylation of HIP-55 S269 and T291, dysregulated phase separation, and subsequent aggregate formation of HIP55. Moreover, we demonstrated the important role of dynamic phase separation of HIP-55 in inhibiting hyperactivation of the beta-adrenergic receptor-mediated P38/MAPK (mitogen-activated protein kinase) signaling pathway. A phosphorylation-deficient HIP-55 mutation, which undergoes massive phase separation and forms insoluble aggregates, loses the protective activity against HF.CONCLUSIONS:Our work reveals that the phosphorylation-regulated dynamic phase separation of HIP-55 protects against sympathetic/adrenergic system-mediated heart failure.

An efficient palladium-catalyzed intramolecular annulation of 1-acylamino-o-carboranes has been achieved for the synthesis of o-carboranoxazoles with good to excellent yields across a wide range of substrates. Chlorobenzene, acting as an external oxidant, plays a crucial role in this intramolecular dehydrogenative cross-coupling reaction.

Degradation of carbon-backbone polymers, which make up most plastics, remains a formidable challenge owing to strong and inert main-chain C-C bonds. While incorporation of comonomers that generate backbone radicals under certain conditions can induce degradation of the polymer chain, such strategies yield complex oligomer mixtures. Here we report aromatization-driven C-C bond cleavage as a viable and powerful strategy to endow the degradability into carbon backbones using acrylic polymers as a model example. The key to this new strategy is the efficient, living, alternating addition copolymerization of acrylates with simple, commercially available and biorenewable coumarin using a frustrated Lewis pair cooperative catalyst. The resulting acrylic copolymers are strong, transparent thermoplastics with key thermal, optical, mechanical properties comparable or superior to poly(methyl methacrylate). Under strong base, alternating copolymers can completely degrade at room temperature through efficient cleavage of main-chain C-C bonds utilizing aromatization as a thermodynamic driving force, to generate pure, pharmaceutically valuable molecules, thus affording durable, robust yet fully degradable carbon-backbone acrylic polymers.