Herein we reported metal-free oxidative chloro- and bromodifluoromethylation of thiophenols with TMSCF2X in the presence of oxidant N-chloro(bromo)succinimide and n Bu4NX (X = Cl or Br), respectively, under mild reaction conditions. This protocol provided a practical and efficient method for synthesizing various biologically valuable and synthetically challenging chloro- and bromodifluoromethyl aryl sulfides. Preliminary mechanistic investigation suggested that the transformation proceeded through a difluorocarbene intermediate.

Biomedical hydrogels are integral to a wide range of applications, with their efficacy critically hinging on precise delivery and successful gelation at targeted sites. Nevertheless, existing technologies that provide reliable, visual confirmation of gelation and accurate localization remain very limited. Here organic afterglow emitters are reported that are designed with small phosphorescence rate (k P approximate to 0.04 s-1), small nonradiative decay rate (k nr approximate to 0.01 s-1), and controllable oxygen quenching rate (k q). The organic emitters exhibit no afterglow in liquid state under ambient conditions. Upon hydrogel formation, the organic emitters, embedded within the as-formed biomedical hydrogel, demonstrate bright and persistent afterglow with phosphorescence lifetimes extending up to 15.82 s. This gelation-induced afterglow, characterized by a high on/off contrast, facilitates a visual observation of successful hydrogel formation and precise localization of biomedical hydrogels. In-depth studies reveal that, within the biomedical hydrogel, the diffusion of oxygen is significantly impeded and oxygen concentration is also reduced, leading to a substantially small k q of the organic emitter (approximate to 0.02 s-1) and subsequent emergence of the afterglow. This study presents a novel afterglow-based approach for visualizing hydrogel formation and localization, and meanwhile offering an innovative strategy to achieve high-performance organic afterglow in soft matter systems.

Biosynthesis of free fatty acids (FFAs) in mammals is pivotal for metabolic homeostasis, yet a comprehensive understanding of tissue-specific biosynthesis and inter-tissue crosstalk of FFAs remains incomplete. In vivo stable-isotope tracing metabolomics is utilized to comprehensively measure FFA biosynthesis and inter-tissue crosstalk in mice. Systematically assessing tissue-specific biosynthesis of 13 FFAs across 15 tissues unveils dynamic spatial and temporal accumulation and redistribution of FFAs throughout the body. Employing an analytical framework to deconvolve mass isotopologue patterns, inter-tissue crosstalk is explored for saturated, polyunsaturated, and monounsaturated FFAs, and quantify communications of FFA (16:0) and FFA (18:0) between the liver and other tissues. Then, a decline in fatty acid biosynthesis in peripheral tissues but not in the brain of aged mice is observed, particularly evident in palmitic acid and monounsaturated fatty acids. These findings illuminate the complex interplay between tissue-specific fatty acid biosynthesis and the maintenance of metabolic homeostasis.

Polymethacrylate (PMMA) has held a long-standing interest in materials science due to its good processability, considerable optical and mechanical performance, and low price. However, the current challenge lies in maintaining high thermal stability across a wide temperature range for PMMA-based materials. Herein, a series of perfluorocyclobutyl (PFCB) aryl ether-containing PMMA copolymers were prepared to improve the heat resistance of PMMA-based materials via introducing PFCB moiety and forming crosslink network structures. First, a 4-(2-(4-methoxyphenoxy)perflurocyclobutoxy)-[1,1'-biphenyl]-4-ylmethyl methacrylate (PFBMA) monomer with PFCB moiety was copolymerized with methyl methacrylate (MMA) to provide PFCB-containing PMMA copolymers with exceptional thermal stability. Subsequently, a dimethacrylate monomer containing PFCB moiety was synthesized and copolymerized with MMA, resulting in crosslinked PMMA copolymers where PFCB served as a connection point. The resulting crosslinked PMMA copolymers showed higher glass transition temperature (T g) and thermal decomposition temperature (T d) than those of PMMA, along with exceptional optical transparency. This study not only establishes an efficient synthetic route for the preparation of PFCB-containing PMMA copolymers but expands the structural diversity of functional polymers.

Cyclobutane-fused heterocycles are important motifs in biologically active molecules, yet their enantioselective synthesis remains a significant challenge. We report a broadly applicable and modular strategy for constructing these strained architectures through a visible-light-mediated, Lewis acid-catalyzed dearomative [2+2] photocycloaddition of indoles, benzofurans, and benzothiophenes with alkenes. The method employs a simple catalytic system based on commercially available rare-earth Lewis acids and chiral pyridine-2,6-bis(oxazoline) (PyBox) ligands. A wide array of heteroarenes and styrenes bearing diverse functional groups participate efficiently, delivering cyclobutane-fused products in up to 96% yield, >20:1 dr, and >99% ee. The synthetic utility is further demonstrated by gram-scale synthesis and facile removal of the directing group to access functionalized amino acid derivatives. Mechanistic investigations, including ultraviolet-visible (UV-vis) spectroscopy, nonlinear effect studies, kinetic isotope effects, and density functional theory (DFT) calculations, reveal that a triplet-state heteroarene engages in regio- and enantio-selective C & horbar;C bond formation under mild photochemical conditions. This study highlights the potential of excited-state Lewis acid catalysis in unlocking enantioselective dearomatization pathways for complex molecular architectures.

Catalytic diastereo- and enantioselective functionalization of cyclobutenes represents a general and modular strategy for the construction of enantioenriched complex cyclobutanes. However, all precedents focused on reactions of cyclobutenes with nucleophilic organometallic intermediates, whereas transformations of cyclobutenes with electrophiles remained unknown. Herein, we report an unprecedented cobalt-catalyzed protocol for diastereo- and enantioselective reductive coupling of unactivated cyclobutenes and aldehydes. This process enabled access to a broad range of densely functionalized enantioenriched cyclobutanes and the introduction of a chiral functionalized alkyl group with high efficiency and stereoselectivity. Mechanistic studies revealed that diastereo- and enantioselective oxidative cyclization of cyclobutenes and aldehydes followed by stereoselective protonation might be involved. DFT (Density Functional Theory) calculations elucidated the origin of stereoselectivity. This study provides a new platform for modular synthesis of enantioenriched cyclobutanes and reveals new reactivity for cobalt catalysis, pushing forward the advancement in organocobalt chemistry.

Branched PFOA and PFOS have shorter half-lives, lower toxicity, and weaker serum protein binding than linear ones, offering better environmental and health safety. Yet methods to access such branched motifs remain under developed. We now introduce a one-step dehydroxy-perfluoro-tert-butylation of alcohols, in which perfluoro-tert-butyl phenyl sulfone serves both to activate the C-O bond and to deliver the perfluoro-tert-butyl group. Mechanistic studies-including DFT calculations-reveal that perfluoro-tert-butyl phenyl sulfone first generates perfluoroisobutylene in situ to effect C-O bond cleavage, after which a catalytic iodide engages in the C-C bond-forming event. Remarkably, the isolated perfluoro-tert-butyl anion salt, characterized by single-crystal X-ray diffraction, displays significant negative hyperconjugation, as evidenced by the elongated C-F bonds. This operationally simple protocol tolerates a wide array of functional groups and complex substrates, providing rapid access to branched perfluoroalkyl scaffolds with broad implications for drug discovery and advanced materials.

Sulfur-stereogenic sulfinamides are not only key structures for biologically active molecules, ligands, and organocatalysts but also versatile intermediates to access a variety of organosulfur compounds containing S(IV) or S(VI) stereogenic centers. Despite progress in this field, catalytic enantioselective construction of sulfur-stereogenic centers remains a significant challenge. Herein, we present a cobalt-catalyzed protocol for catalytic enantioselective aryl and alkenyl addition to sulfinylamines with aryl and alkenyl boronic acids, affording a broad scope of sulfur-stereogenic sulfinamides with high efficiency and enantioselectivity. A phosphorus-stereogenic phosphinooxazoline ligand was developed, enabling the introduction of alkenyl groups onto the sulfur-stereogenic centers. Functionalization provided a variety of sulfur-stereogenic S(IV) and S(VI) compounds. Mechanistic studies and DFT calculations have been conducted to elucidate the reaction mechanism and the origin of enantioselectivity.

Two-dimensional covalent organic frameworks (2D COFs) have emerged as promising photocatalysts due to their high surface areas and precisely tunable physicochemical properties. However, it remains a significant challenge to precisely control over interlayer stacking configurations in 2D COFs, which critically influence charge carrier transport and consequently determine catalytic efficiency. In this study, we demonstrate a solvent-driven strategy to precisely regulate the interlayer stacking configurations of metal-incorporated 2D COFs, successfully achieving both AA eclipsed (COF-TD-AA) and ABC staggered (COF-TD-ABC) configurations. Notably, by modulating the coordination interactions between solvent 1-butanol and Zn2+ (within the COFs), the interactions between the Zn2+ and nitrogen atoms (from imine bonds, pyridine, and triazine units) can be precisely tuned, which leads to the formation of AA or ABC stacked 2D COFs. Interestingly, the ABC-stacked COF-TD-ABC exhibited an extended light absorption and superior charge migration/separation efficiency than those of COF-TD-AA. As a result, when coupled with Pt co-catalysts, COF-TD-ABC achieved a high hydrogen evolution rate up to 10.92 mmol g-1 h-1, representing a similar to 3.5-fold enhancement over COF-TD-AA (3.12 mmol g-1 h-1). This work provides a fundamental insight into the stacking-dependent structure-property relationships in COFs, paving the way for the rational design of high-performance COF-based photocatalysts.

Pancreatic ductal adenocarcinoma (PDAC) remains refractory to current immune checkpoint blockade (ICB) therapies, necessitating innovative therapeutic strategies. Emerging evidence implicates aberrant sialoglycan upregulation as a key mediator of immune evasion in PDAC. Herein, we report Y-320, a highly potent oral sialylation inhibitor discovered through high-throughput screening. Y-320 suppresses alpha-2,3/2,6-sialylation in PDAC cells (IC50 approximate to 200 nM) with >300-fold higher activity than the known pan-inhibitor P-3F(ax)-Neu5Ac. Structural analyses reveal competitive occupation of multiple sialyltransferases' substrate-binding pockets as Y-320's action mechanism. In vivo, Y-320 significantly inhibits tumor growth and remodels the tumor immune microenvironment. Mechanistic studies establish that the therapeutic efficacy of Y-320 depends on the coordinated engagement between CD8(+) T cell and macrophage. Importantly, Y-320 synergizes with anti-PD-1 therapy to overcome ICB resistance in PDAC, demonstrating superior tumor suppression compared to monotherapies. Our findings demonstrate that Y-320 shows promise for use as a therapeutic agent for cancer and validates sialylation inhibition as a novel glycoimmune checkpoint strategy for PDAC and other immunotherapy-resistant malignancies.