A Pd(II)-catalyzed oxime ether-directed γ-C(sp3)-H activation of masked aliphatic alcohols has been developed, enabling selective C-O bond formation with electron-deficient pyridones. The use of N-fluorobenzenesulfonimide (NFSI) as a key oxidant is crucial for over-riding the conventional β-selectivity, thereby affording γ-functionalized products. This transformation exhibits a broad substrate scope and a high functional group tolerance. Overall, this strategy provides an efficient and practical approach to pyridone ether synthesis via remote C-H activation.

N-Demethylation of the N,N-dimethylaminophenyl group is a useful transformation, but typically requires harsh reaction conditions, stepwise procedures, or the use of unrecoverable catalysts. Herein, we report a photoinduced N-demethylation of N,N-dimethylaminophenyl derivatives using a fully conjugated donor (D)-acceptor (A) covalent organic framework (Py-BSZ-COF(CC)) as an efficient and recyclable photocatalyst. Owing to the excellent light-harvesting capability, suitable band gap, and favorable kinetics of photogenerated-exciton separation and transfer in Py-BSZ-COF(CC), the reaction proceeded under mild conditions with broad substrate tolerance, affording the N-demethylated products in good yields. Notably, this transformation is easily scalable to the gram scale, and the catalytic activity of Py-BSZ-COF(CC) is well maintained over five successive runs. Comparative analysis among the structurally related COFs underscores the critical role of the fully conjugated D-A architecture in driving photocatalysis. This study highlights the potential of COFs in photocatalysis and offers a paradigm for developing efficient and practical N-demethylation reactions.

Organic cage-like frameworks can serve as crucial skeletal structures for the development of prospective energetic materials owing to their high inherent density, symmetry, and derivability. Herein, we show the construction of a novel nitrogen-containing cage-like framework, 9-azatricyclo[4.2.1.03,7]nonane-2,5-diol, from bicyclo[3.3.0]octane-2,6-diene. Thereafter, its two energetic derivatives were also prepared and characterized. The results of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) show that the energetic derivatives possessed satisfactory thermal stability, and the calculation results (D = 8196 ms-1 and 7343 ms-1, P = 29.9 and 21.68 GPa) show good detonation performance, which implies that the 9-azatricyclo[4.2.1.03,7]nonane frameworks have the potential to be used for preparing new 3D energetic compounds with superior energy performance.

Oxaadamantane has emerged as a promising parent framework in recent years for designing and synthesizing advanced energetic materials. Herein, a novel cage-like energetic compound, (endo)-8,8,9,9-tetranitro-2,4,10-trioxaadamantan-6-yl nitrate, was synthesized from inositol via eight linear steps. It exhibits a high single-crystal density (ρ = 1.933 g·cm-3), acceptable thermal stability (Td = 158 °C), reasonable oxygen balance (OBCO = 18.80%), outstanding detonation performance (D = 8763 m·s-1; p = 35.49 GPa) and acceptable mechanical sensitivity (IS = 10 J; FS = 192 N). Additionally, the lead plate test demonstrated that its detonation performance is comparable to that of RDX. These results imply that the as-prepared compound has the potential to be used as high energy density materials.

Developing efficient and multifunctional sonosensitizers is critical for enhancing the efficacy of sonodynamic therapy (SDT). Herein, a dual enzyme-mimicking sonosensitizer, termed sonozyme, is prepared for improving the management of malignancy in SDT via cascade oxygenation and reactive oxygen species (ROS) storm, which consists of a tailored covalent organic framework (Y-COF) integrated with platinum nanoparticles (Pt NPs). Spatially separated donor-acceptor structural design optimizes the band position of Y-COF, which endows sonozyme with good intrinsic sonodynamic activity. Notably, Pt NPs improve the sono-generated exciton separation and transfer dynamics, further enhancing the ultrasound-triggered ROS generation ability of sonozyme. Particularly, sonozyme exhibits dual enzymatic activities, resembling both catalase (CAT) and peroxidase (POD), which enable the conversion of endogenous H2O2 into O2 and ·OH, thereby alleviating hypoxia while augmenting oxidative stress to enhance the SDT effect, ultimately resulting in significant tumor cell death. Further in vivo experiments demonstrate that sonozyme effectively suppresses tumor progression with concomitant absence of observable systemic toxicity under ultrasound irradiation. Therefore, sonozyme provides a paradigm for pioneering high-performance multifunctional sonosensitizers and presents a promising strategy for cancer therapy.

Piezocatalytic therapy (PCT) has garnered increasing interest in the field of cancer treatment. However, its therapeutic efficacy is hampered by the limitations of current piezoelectric materials and the intrinsic therapeutic resistance of tumors. Here, leveraging elaborately designed copper-coordinated covalent organic frameworks (CuCOF-2 N) as piezocatalysts, a smart ultrasound-controlled nanoreactor (Cu2N@D-FA) is constructed by co-encapsulating with doxorubicin prodrug into folic acid-modified liposomes, to enhance the antitumor efficacy of PCT through the combination of cuproptosis and bioorthogonal catalysis. The structure-property comparison with related COFs underscores the important role of highly polar triazine rings and symmetry-disrupting bidentate ligands in enhancing piezoelectric performance of CuCOF-2 N. Upon ultrasound irradiation, CuCOF-2 N not only produces hydroxyl radicals independently of oxygen but also enables a self-sustained oxygen supply for generating superoxide anions and singlet oxygen, which surmount constraints of traditional piezoelectric materials to trigger strong PCT. Moreover, the mediated-copper valence switching in CuCOF-2 N permits spatiotemporally precise bioorthogonal catalysis and triggers cuproptosis, overcoming therapeutic limitations and amplifying the PCT effect. In vivo studies demonstrate that Cu2N@D-FA selectively accumulates in the tumor and effectively eliminates the tumor without side-effects under US stimulation. Therefore, this study highlights the great promise of COFs in piezocatalysis and offers a paradigm for enhancing PCT. STATEMENT OF SIGNIFICANCE: A sonopiezoresponsive copper-coordinated covalent organic framework is designed and co-encapsulated with a doxorubicin prodrug in folic acid-modified liposomes to enable synergistic piezocatalytic therapy. The CuCOF enables oxygen-independent hydroxyl radical generation while providing a self-sustained oxygen supply for the production of superoxide anions and singlet oxygen. Ultrasound triggers reversible valence state switching of copper within the framework, enabling in situ bioorthogonal catalysis, and the concomitant mitochondrial accumulation of copper induces cuproptosis. The CuCOF-based nanoreactor demonstrates good biocompatibility and achieves potent tumor suppression under mild ultrasound irradiation.

Rapid systemic elimination of drugs remains a significant challenge in cancer therapy. Herein, an isotope substitution strategy is employed to enhance the therapeutic potential of a novel nitric oxide and formaldehyde co-donor, 3,5-dinitro-1,3,5,7-tetraaza[3.3.1] nonane (DPT), by modulating its metabolic fate and improving its pharmacokinetic behavior. Based on the parent compound, deuterated (DPT-d10), nitro-15N-substituted (DPT-15N2), and dual-modified (DPT-15N2 + d10) derivatives were synthesized. These isotope substitution derivatives retain the electronic properties and functional integrity of the original molecule while slowing the metabolic rate of both the parent compound and its active components (formaldehyde and nitric oxide), which prolongs in vivo residence time, leading to enhanced tumor growth inhibition with minimal adverse effects. Notably, benefiting from the synergistic isotope effects of deuteration and nitro-15N substitution, DPT-15N2 + d10 exhibits superior antitumor activity. Therefore, this study establishes a paradigm for overcoming the limitation of rapid systemic clearance in anticancer drug development.

Energetic cocrystals can achieve a balance between detonation performance and stability. However, the formation of cocrystals of compounds with highly similar structures remains rather challenging. Herein, a large block-shaped energetic cocrystal (8 mm × 5 mm) of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclootane (HMX) and its key precursor and structural analogue 1-nitroso-3,5,7-trinitro-1,3,5,7-tetraazacyclootane (MNX), were obtained through volatilization crystallization. The cocrystal was confirmed by single crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, nuclear magnetic resonance and other identification methods. The molar ratio of HMX to MNX in the cocrystal was determined to be 3:2. The friction sensitivity of the cocrystal is lower than that of β-HMX, and the detonation performance is between the two components. This protocol provides a new analytical observation point for confirming multicomponent cocrystals with structurally similar components through single-crystal analysis.

Accurate quantification of Zn2+ is crucial for food quality control and nutritional assessment, whereas sensitive detection of Cd2+ is vital for food safety assurance and aquatic environmental protection. Herein, we report the design and synthesis of DSYQ, a near-infrared (NIR) dual-channel fluorescent probe. DSYQ exhibits exceptional selectivity toward Zn2+ and Cd2+, producing distinct NIR fluorescence responses with large Stokes shifts. The probe demonstrates ultra-sensitive detection capabilities in complex food matrices. Moreover, DSYQ shows outstanding biocompatibility and versatile imaging capabilities, enabling the simultaneous real-time monitoring of endogenous Zn2+ fluctuations and exogenous Zn2+/Cd2+ uptake in 4T1 cells. In vivo experiments demonstrate its ability to track metal ion dynamics in tumor-bearing mouse models. Compared to existing methods, this probe integrates near-infrared emission, high sensitivity, and a large Stokes shift, allowing it to effectively address complex practical application requirements. However, further validation and field-level evaluation are still required for routine deployment.

Zinc ions (Zn2+) are essential for human health, and their accurate detection in food is critical for dietary safety and nutritional assessment. Although near-infrared fluorescent probes have been widely developed for Zn2+ detection, their application in complex food matrices remains underexplored. Herein, we report DCMB, a novel near-infrared probe based on a dicyanomethylene-4H-pyran (DCM) derivative, exhibiting high selectivity for Zn2+ with an emission maximum at 640 nm. Anti-interference was systematically evaluated against metal ions, food-relevant small molecules, and biomolecules. DCMB enabled accurate Zn2+ quantification in diverse food matrices: fruits (apples, bananas), dairy products (milk), cereals (oats), and pharmaceuticals (zinc gluconate tablets), with results consistent with inductively coupled plasma mass spectrometry. DCMB-loaded test strips allowed rapid and portable naked-eye visual detection and smartphone-based RGB analysis of Zn2+ in food and supplement samples. Moreover, DCMB facilitated real-time tracking of endogenous and exogenous Zn2+ in 4T1 cells and supported in vivo imaging in mice, with effective suppression of background autofluorescence. Together, DCMB enriches the repertoire of near-infrared fluorescent probes for Zn2+ detection in complex food matrices.

Abstract Oxalyl dihydrazide (ODH) is a polymorphic organic compound, and distinct ODH polymorphs possess disparate physicochemical properties, including melting point, solubility, and dissolution kinetics. Under atmospheric pressure, the dynamic method was applied to obtain solid–liquid phase equilibrium information on α-ODH within the temperature range of 293.15–353.15 K. Twelve pure solvents were selected for the tests, namely, water, ethanol, acetic acid, dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), N-ethyl-2-pyrrolidone (NEP), N,N-dimethylacetamide (DMAC), N,N-diethylformamide (DEF), N,N-dimethylformamide (DMF), 1,3-dimethyl-2-imidazolidinone (DMI), hexamethylphosphoramide (HMPA), and formamide. Experimental results indicated that the solubility of α-ODH monotonically increased with the increase in temperature in all tested solvents. Three thermodynamic models (van’t Hoff equation, Yaws model, and the modified Apelblat equation) were employed to correlate the measured solubility data. In addition, the dissolution thermodynamic properties (Gibbs free energy, entropy, and enthalpy) of α-ODH in the tested solvents were calculated based on the experimental solubility data and the van’t Hoff equation. Moreover, Hirshfeld surface analysis was implemented to characterize dominant intermolecular contacts inside the α-ODH crystal lattice. The acquired solubility data offers reliable fundamental support for industrial crystallization optimization of α-ODH.

Organic cage-like frameworks are important and versatile skeletons for developing prospective energetic compounds because of their high intrinsic density, symmetry, stability, and derivability. In this paper, a noradamantane-based energetic compound 3,7-dinitrato-9-nitro-9-azanoradamantane was synthesized from easily accessible compound 1,6-heptadien-4-ol via eight steps. Based on the X-ray diffraction analysis, it exhibits a good density of 1.678 g.cm-3. Thermogravimetry (TG) and differential scanning calorimetry (DSC) tests indicate that it has positive thermal stability since its decomposition temperature was found to be 134 degrees C, and the theoretical detonation velocity is calculated to be 7363 m.s-1. These results imply that noradamantane has the potential to be a prospective framework for developing high energy-density energetic compounds.

Accurate identification of organic pesticides (OPs) is of great importance in agriculture, food safety and environmental protection. Due to the increasing number and greatly diversified structures, developing a rapid and universal strategy for OPs identification still remains a challenge. Herein, a fluorescence sensor array based on covalent organic frameworks (COFs) is designed to identify different types of OPs. The topologies of COFs are rationally designed by customizing the monomer and linkage structures to construct the fluorescence sensor array. Twenty-eight OPs with different core structures, including phenyl rings, five-membered heterocyclics, fused- and mixed-rings, are unambiguously discriminated ranging from 5 mu M to 1 mM. The resulting sensor array exhibits excellent selectivity against a variety of interferents. Importantly, the mechanism of the sensor array is investigated by quantitative structure-activity relationships (QSAR). Multiple linear regression (MLR) models are established to evaluate and predict the Stern-Volmer constants and binding constants, revealing direct connections between the fluorescence signals and OP structures. Eleven molecular descriptors feature the determining factors for the signal outputs. The QSAR analysis contributes to the development of sensor arrays and provides a novel approach to multivariate analysis.

Pd(II)-catalyzed gamma-C(sp(3))-H (hetero)arylation of aliphatic ketones is developed using acetohydrazide as the transient directing group (TDG). The reaction is facilitated by a crucial 2-pyridone ligand via the 5,6-membered fused palladacycle intermediate, enabling the smooth gamma-C(sp(3))-H (hetero)arylation of various aliphatic ketones. The reaction demonstrated tolerance to different functional groups of aryl iodides, and compatibility with various pyridinyl or quinolinyl iodides. Furthermore, regioselectivity of gamma-C(sp(3))-H arylation with current reaction conditions was compared with previous studies for the challenging substrate pentan-2-one.

Crystal vacancies play a crucial role in modulating material properties, yet achieving precise control over vacancy formation remains a significant challenge. Intriguingly, conventional characterization techniques such as X-ray diffraction analyses (powder XRD, single-crystal XRD) typically show negligible differences before and after vacancy generation in crystalline materials. In this work, a novel strategy is designed to construct crystal structures with tailored vacancies through multivariate cocrystallization. First, the polymorphs of two organic small molecules HMX and MNX with analogous electron cloud distributions were identified and summarized, and a new crystal form of MNX was discovered. Second, seven binary MNX-based cocrystals were synthesized, along with analysis of disorder characteristics and comparative studies of their HMX counterparts. Among them, HMX-DMF and MNX-DMF cocrystals were selected based on their nearly identical XRD patterns. Third, computational simulations of charge distributions in these cocrystals confirm the feasibility of ternary cocrystal formation. Finally, through simple cooling crystallization, the HMX-MNX-DMF ternary cocrystal was successfully obtained, which exhibited the anticipated oxygen vacancies. This systematic screening and construction methodology provides a powerful tool for designing vacancy-engineered crystals tailored for potential specialized applications.

A PdII-catalyzed ortho-C(sp²)−H hydroxylation of benzyl alcohols using oxime ether as a monodentate directing group was developed. The N-acetyl glycine ligand is crucial to the reactivity through facilitating the C−H cleavage. The reaction might involve the formation of hydroxyl radicals generated from oxone and a 6-membered exo-palladacycle intermediate was proposed. Various substituents on the phenyl ring were tolerated in the reaction. Gram-scale reaction and directing group removal were also demonstrated to show its applicability for the syntheses of salicyl alcohols.

The synthesis of azaadamantane-based energetic compounds with symmetrical structures and numerous explosophoric groups has always been a major challenge in the field of energetic materials. Herein, we report the synthesis of a fully bridged carbon-substituted 2-azaadamantane energetic compound with seven explosophoric groups. It exhibits a high crystal density (1.90 g cm-3) and excellent detonation properties (D = 8881 m·s-1, P = 37 GPa), which show that it has the potential to be applied as a high-energy density material.

Recent insights into covalent organic frameworks (COFs) provide an opportunity for developing new sonosensitizers with the advantages of both small molecules and inorganic nanoagents. Herein, we synthesize two benzotrithiophene-based imine-linked COFs (BTT-DPh-COF and BTT-DPy-COF) through density-functional-theory-guided structure editing. The tailored donor-acceptor (D-A) structures optimize the band position of the COFs and endow them with good intrinsic sonodynamic activity, which can efficiently kill cancer cells, showing excellent sonodynamic therapeutic effect. Particularly, because of the enhanced D-A effect that promotes charge separation and transfer behavior, BTT-DPy-COF exhibits superior ultrasound-triggered reactive oxygen species (ROS) generation capability than BTT-DPh-COF. Therefore, these studies highlight the great potential of elaborate editing COFs with D-A configurations as suitable candidates for advanced sonosensitizers.

Zinc levels in living organisms and the environment are vital to human health and the environment. Therefore, rapid and highly sensitive methods for detecting Zn2+ are required. Herein, a novel fluorescent probe (APYQ) was synthesized by a simple Schiff base reaction. APYQ exhibited high selectivity to detect Zn2+ without interference from other metal ions. The limit of detection (LOD) as low as 1.87 nM, and response time as fast as 5 s. These two indicators had the best overall performance compared to other Zn2+ probes over the past five years. Single crystals of APYQ and APYQ-Zn2+ complex were successfully obtained, indicating that the fluorescence enhancement induced by the large conjugated rigid plane structure of the complex may rationalize the superb detection limit. The intramolecular charge transfer (ICT) and chelation-enhanced fluorescence (CHEF) mechanism was proposed based on Job's plot, ESI-MS, NMR titration and DFT calculation. Moreover, APYQ possessed the capability to detect Zn2+ in water samples and test strips in a qualitative and quantitative manner. Furthermore, APYQ has been effectively used to detect Zn2+ intracellularly in Hela cells. This work provides a substantially enriched probe arsenal for the detection of Zn2+ with high sensitivity and fast response.

All bridge-carbon nitrato-functionalized diheteroadamantanes and their structural isomers with high density and excellent detonation performance were synthesized in three steps.