Herein, we describe a method in the one-pot synthesis of cyclic 1,3-enynes and allenynes from alkynyl-allenyl cross-coupling and cascade reactions of vinylidenecyclopropane-diesters (VDCP-diesters) with a large number of unactivated terminal alkynes for the formation of a C(sp(2))-C(sp) bond under palladium/copper dual catalysis and assisted by base Cs2CO3 and NEt3 with distinctly different Br & oslash;nsted basicity and Lewis basicity. This developed divergent transformation proceeds through a key rapid transmetalation and the subsequent intramolecular cyclization process regulated by cesium effect. Our investigations found that these reactions can occur under mild conditions and have a broad substrate scope with a wide range of functional groups via a zwitterionic palladium species, affording the corresponding desired products in moderate to good yields. Further synthetic transformations show the application value of this protocol. Plausible reaction mechanisms have also been proposed on the basis of control, deuterium labeling experiments, and density functional theory calculations.

Organic afterglow materials have garnered significant attention due to their long-lived excited states, demonstrating promising applications across diverse fields. Over the past few decades, these materials have experienced rapid development, particularly dopant-matrix systems. This review focuses on the progress made in dopant-matrix organic afterglow materials over the past three years, emphasizing two key aspects: high-performance organic afterglow materials and the critical role of organic matrices in materials fabrication. In the first section, we summarize strategies for enhancing afterglow performance through molecular design, focusing on representative luminescent systems such as benzophenone derivatives, polycyclic aromatic hydrocarbons, and difluoroboron beta-diketonate compounds. The second section explores the pivotal functions of organic matrices, including protecting triplet excited states, facilitating intersystem crossing, sensitizing triplet states, and promoting charge separation, which collectively contribute to novel functionalities of afterglow materials. Beyond the molecular design of luminophores, the selection of organic matrices is equally crucial for achieving high-performance afterglow materials and expanding their functionality. This review provides a comprehensive compilation of chemical structures for various organic matrices, serving as a valuable reference for researchers. Given the intricate photophysical processes in organic afterglow systems, we also present experimental methods that support or refute specific mechanisms, providing critical insights for future studies. Overall, dopant-matrix organic afterglow materials represent a highly promising class of luminescent materials. We anticipate their large-scale adoption and high-value applications in real-world scenarios in the near future.

The perfluoro-tert-butyl group (PFtB) stands out, in part, due to its unparalleled analytical capabilities, as an indispensable functional group for sensing and imaging within biological systems. Although previously we have accomplished the introduction of the perfluoro-tert-butyl group into sp3-and sp2-carbons, the perfluoro-tert-butylation of sp-carbon remains a challenging task. In this study, we develop a versatile method to construct structurally diverse PFtB-substituted alkynes, utilizing (perfluoro-tert-butyl)propiolic acid (PFtPA) as a new reagent. PFtPA is easy to synthesize and can undergo Pd/Cu-catalyzed decarboxylative coupling with a wide array of (aryl, alkyl, alkenyl, and alkynyl) halides and triflates. This synthetic protocol is not only high-yielding but also compatible with various functional groups. Furthermore, we demonstrate the potential of this new synthetic protocol by developing a 19F-labeled probe that is proficient in distinguishing analytes with distal chiral centers.

Background: Bolting severely affects the medicinal value and yield of Saposhnikovia divaricata. Currently, spatial distribution of secondary metabolites in bolted and unbolted Saposhnikovia divaricata remains unknown. The commercial Mass spectrometry imaging (MSI) platforms has high sensitivity to high-polar compounds, but suppresses signals of less polar compounds, generating a gap of understanding how spatial distributed of such metabolites that is less prone to ionize. Results: This study developed a highly sensitive Laser Ablation Carbon Fiber Ionization (LACFI) MSI method under atmospheric pressure to achieve the spatial distribution analysis of secondary metabolites in Saposhnikovia divaricata, including low-polar compounds which is difficult to be analyzed in other MSI methods. The laser efficiently desorbs compounds from Saposhnikovia divaricata tissue, and the desorbed compounds are rapidly ionized by a carbon fiber ion source under high pressure. The desorption and ionization are performed in two separate steps, reducing the matrix effect and enhancing the ionization efficiency of compounds, which increase sensitivity. The carbon fiber has good compatibility with polar and low-polar compounds, which increases the number of detectable metabolites. The spatial distribution of secondary metabolites undergoes a shift from the unbolted to the bolted Saposhnikovia divaricata. The result of imaging is consistent with the conclusion of pharmacopoeia that the bolted Saposhnikovia divaricata is not used medicinally. Significance: Compared to commercial imaging methods, the LACFI-MSI method developed is ultra-sensitive, has a greater sensitivity in the analysis of less polar compounds. Spatial distribution analysis of secondary metabolites that previously difficult/unable to detect in bolted and unbolted Saposhnikovia divaricata is realized.

A C(sp3)-H allylation of tetrahydroisoquinolines has been developed by combining Shono oxidation with a vinylogous Mannich-type reaction. TEMPO was used as the electrocatalyst to lower the electrode potential, improving functional group compatibility. This method provided a practical and efficient tandem procedure for the alpha-allylation of tetrahydroisoquinolines. The reaction proceeded through the formation of an iminium cation intermediate, which was generated in situ by anodic oxidation, followed by nucleophilic addition of 2-allylazaarenes.

Hepatitis B virus infection remains a significant global health challenge, particularly in endemic regions like Vietnam. This article examines the groundbreaking study by Nguyen et al, which investigates the relationship between human leukocyte antigen-DP/DQ polymorphisms and hepatitis B virus-related liver disease progression. Through advanced multi-clustering analysis, the study reveals that the A-A-A haplotype (rs2856718-rs3077-rs9277535) provides protection against disease progression, while the G-G-G haplotype correlates with increased hepatocellular carcinoma susceptibility. The integration of machine learning approaches with genetic data offers promising avenues for refined disease prediction and personalized therapeutic strategies. This article discusses the implications for expanding study populations, implementing longitudinal cohort studies, and leveraging artificial intelligence for improved patient outcomes.

Dehydroxymethylation offers intriguing synthetic opportunities to exploit the ubiquitous C-C bonds in free alcohols as unconventional functional handles; however, its synthetic potential has been constrained by the development of efficient catalysts. In this work, we introduce a robust, bench-stable cerium(IV) benzoate complex, [Ce(TRIPCO2)5Na], which functions as an efficient ligand-to-metal charge transfer (LMCT) catalyst, enabling selective cleavage of alpha-C(sp3)-C(sp3) bonds in free alcohols. This cerium(IV) catalyst is straightforward to synthesize on a gram scale, providing simple conditions for dehydroxymethylation reactions while eliminating the need for exogenous halide additives. The catalytic efficiency of this complex has been demonstrated in the dehydroxymethylative amination of free alcohols and the seamless one-pot synthesis of N-alkyl pyrazoles. Furthermore, the cerium-LMCT catalyst demonstrates efficacy within a metallaphotoredox paradigm, where the synergistic interplay between cerium-LMCT and nickel catalysis facilitates dehydroxymethylative alkylation, enabling the efficient utilization of alcohol feedstocks for selective C(sp3)-C(sp3) cross-coupling reactions. Mechanistic investigations have elucidated the photoexcitation and redox properties, revealing the selective generation of alkoxy radical intermediates in the presence of benzoate ligand, a critical factor in enabling radical-mediated bond cleavage.

Here, we report the Cu-catalyzed asymmetric carbene insertion into both Ge-H and Si-H bonds with alpha-trifluoromethyl diazo compounds, enabled by a class of newly developed C 2-symmetrical bisoxazoline ligands. This protocol provides an efficient method for the preparation of enantioenriched alpha-trifluoromethyl ogranogermanes and organosilanes, featuring a broad substrate scope, mild reaction conditions, excellent enantioselectivity, and low catalyst loading. The key to the tolerance of both Si-H and Ge-H bonds is the use of SPSiBox ligands bearing a flexible and tunable chiral pocket. Preliminary mechanistic studies and computational studies unveiled the origin of chiral induction with SPSiBox ligands, the mechanism of Cu-catalyzed Ge-H insertion. This method not only provides a new method for the construction of trifluoromethyl-containing chiral molecules but also opens a new avenue for the preparation of chiral Si- and Ge-containing functional molecules.

The selective introduction of a single functionality on the upper rim of calix[4]arene is challenging due to the identical reactivity of its four aryl units. In this study, we introduce a novel strategy for monofunctional modification of calix[4]arenes using a hypervalent iodine-mediated C-H functionalization. This process yields a calix[4]arene-iodonium salt, which can be easily isolated due to its distinct solubility compared to the native calixarene. This versatile intermediate efficiently undergoes C-O, C-N, and C-S couplings with a variety of nucleophiles, including amines, phenols, thiols, and sulfinate salts under mild conditions. This strategy enables streamlined structural diversification of calix[4]arenes, opening new avenues for the design of supramolecular macrocycles with tailored functions.

Here, we report an efficient method to synthesize enantiomerically enriched propargyl nitriles via copper-catalyzed asymmetric cyanation of propargylic radicals, which are generated from silyl-substituted allenes or alkynes. These reactions proceeded through a highly site-selective hydrogen atom abstraction (HAA) with Cu(II)-bound nitrogen-centered radicals (NCRs). Notably, silyl-substituted allenes demonstrate exceptional allenic sp2 C & horbar;H bond activation selectivity, outcompeting alternative reactive sp3 C & horbar;H bonds (benzylic, allylic, and heteroatom-adjacent) in HAA processes. This chemo-selectivity profile enables precise enantiocontrol and site-specific functionalization of complex molecular architectures.

Neutrophils are the most abundant circulating leukocyte population that play critical roles in neuroinflammation following central nervous system (CNS) injury. CD177, a glycoprotein on neutrophils, is emerging as an important immune regulator which can fundamentally affect multiple human inflammatory diseases. However, the role and regulatory mechanism of CD177 glycobiology of neutrophils in neuroinflammation remain elusive. Here, we show that CD177+neutrophils expand significantly and infiltrate the injured brain following CNS injury both in the human and mouse. Using single-cell RNA sequencing and genetic approaches, we find CD177+ neutrophils as an anti-inflammatory subset that is critical for modulating neuroinflammation after CNS injury. We further identify St3gal5, a sialyltransferase (ST), that can mediate the sialylation and cell surface presentation of glyco-CD177 on neutrophils. Glycoproteomics reveal downregulated sialylation levels in St3gal5-deficient neutrophils. Neutrophil-specific depletion of St3gal5 prevents the cell surface presentation of CD177 on brain-infiltrated neutrophils and exacerbates neuroinflammation. Administration of the FDA-approved anticonvulsant valproic acid (VPA), an St3gal5 upregulator, promotes the glycosylation of neutrophils and attenuates neuroinflammation following CNS injury. Our study reveals a glycoimmuno-regulatory effect of neutrophils and suggests VPA as a neutrophil glycobiology targeting approach to combat neuroinflammation following CNS injury.

Ullmann coupling has been one of the most important organic reactions for the formation of an aryl-aryl bond, which is of great significance in medicinal chemistry, natural product synthesis, and optoelectronic material fabrication. However, the associated reaction mechanism has not been determined with certainty and has mostly relied on theoretical calculations, since the identification of reaction intermediates lacked experimental evidence. Herein, we report the visualization of an unprecedented C-Cu-Br-Cu-C bonded intermediate state of Ullmann coupling by means of on-surface synthesis. These intermediates tend to form nanorings on a Cu(111) surface, as thermodynamically stable structures. Advanced techniques, including scanning tunneling microscopy, non-contact atomic force microscopy, and synchrotron radiation photoemission spectroscopy, together with density functional theory calculations, were used to scrutinize the structural assignments and intermediate transition process at the sub-molecular level. The C-Cu-Br-Cu-C structure is confirmed to be the precursor state of the conventional C-Cu-C intermediate during an on-surface Ullmann reaction, since their coexistence and transformation were observed experimentally. Our findings offer insights into revisiting and understanding the reaction mechanism of Ullmann coupling.

Current radiopharmaceuticals for treating bone metastatic tumors have various limitations. We focus on developing a universal, economical, efficient, and safe novel radiopharmaceutical for bone metastasis treatment. I-131 is a well-established medical radionuclide commonly used for both treatment and diagnosis. Risedronate exhibits strong bone-targeting properties with moderate bone retention. This study explored the combination of these two components and evaluated its biological properties in animal experiments. Based on the experimental results, 131I-risedronate demonstrated high bone-targeting efficiency, low uptake in nontarget organs, and rapid clearance. Notably, at 3 days postadministration, significant bone retention was observed, indicating its potential for sustained therapeutic effects. Additionally, its biodistribution and therapeutic effect can be effectively monitored by SPECT/CT imaging.

Among the leading methods for triggering therapeutic anti-cancer immunity is the inhibition of immune checkpoint pathways. N-glycosylation is found to be essential for the function of various immune checkpoint proteins, playing a critical role in their stability and interaction with immune cells. Removing the N-glycans of these proteins seems to be an alternative therapy, but there is a lack of a de-N-glycosylation technique for target protein specificity, which limits its clinical application. Here, we developed a novel technique for specifically removing N-glycans from a target protein on the cell surface, named deglycosylation targeting chimera (DGlyTAC), which employs a fusing protein consisting of Peptide-N-glycosidase F (PNGF) and target-specific nanobody/affibody (Nb/Af). The DGlyTAC technique was developed to target a range of glycosylated surface proteins, especially these immune checkpoints-CD24, CD47, and PD-L1, which minimally affected the overall N-glycosylation landscape and the N-glycosylation of other representative membrane proteins, ensuring high specificity and minimal off-target effects. Importantly, DGlyTAC technique was successfully applied to lead inactivation of these immune checkpoints, especially PD-L1, and showed more potential in cancer immunotherapy than inhibitors. Finally, PD-L1 targeted DGlyTAC showed therapeutic effects on several tumors in vivo, even better than PD-L1 antibody. Overall, we created a novel target-specific N-glysocylation erasing technique that establishes a modular strategy for directing membrane proteins inactivation, with broad implications on tumor immune therapeutics.

Axially chiral diarylethers and diarylamines show similar configurational stability and represent a distinct class of atropisomers containing two adjacent atropisomeric axes. These scaffolds are prevalent in various biologically active natural products and pharmaceuticals, making their catalytic preparation a hot topic of significant interest in synthetic and medicinal chemistry. The unique axial chirality of diarylethers and diarylamines arises from restricted rotation around C-O and C-N single bonds, leading to a pair of adjacent chiral axes. This Review systematically summarizes synthetic strategies, mechanistic insights, and applications of axially chiral diarylethers and diarylamines, with an emphasis on catalytic asymmetric processes. Catalytic asymmetric approaches enabled by biocatalysis, organocatalysis and transition-metal catalysis are highlighted, and the majority of the present methodologies include desymmetrization and kinetic resolution. By providing a comprehensive overview of the current advances and further perspectives, this Review could serve as a valuable guide for organic chemists, medicinal chemists, and materials chemists working on the syntheses and applications of axially chiral diarylethers and diarylamines.