By using a newly developed 4-hydroxy picolinohydrazide as the ligand, Cu-catalyzed coupling of (hetero)aryl chlorides with sodium aryl sulfonates proceeded smoothly at 130 degrees C to give a series of biarylsulfones in 53%similar to 96% yields. This represents the first metal-catalyzed coupling reaction of (hetero)aryl chlorides with sodium aryl sulfonates. Aryl and heteroaryl chlorides bearing either electron-donating or electron-withdrawing groups were applicable for this coupling reaction.

Metabolite annotation in untargeted metabolomics remains challenging due to the vast structural diversity of metabolites. Network-based approaches have emerged as powerful strategies, particularly for annotating metabolites lacking chemical standards. Here, we develop a two-layer interactive networking topology that integrates data-driven and knowledge-driven networks to enhance metabolite annotation. A comprehensive metabolic reaction network is curated using graph neural network-based prediction of reaction relationships, enhancing both coverage and network connectivity. Experimental data are pre-mapped onto this network via sequential MS1 matching, reaction relationship mapping, and MS2 similarity constraints. The generated networking topology enables interactive annotation propagation with over 10-fold improved computational efficiency. In common biological samples, it annotates over 1600 seed metabolites with chemical standards and >12,000 putatively annotated metabolites through network-based propagation. Notably, two previously uncharacterized endogenous metabolites absent from human metabolome databases have been discovered. Overall, this strategy significantly improves the coverage, accuracy, and efficiency of metabolite annotation and is freely available as MetDNA3.

Catalytic dehydrogenative aromatization (CDA) has emerged as a powerful strategy for the synthesis of substituted phenols. However, most of the known CDA methods suffer from limited functional group compatibility due to the use of strong oxidants, reductants, or bases. Herein, we report a (cis-P2Cl)Ir-catalyzed CDA reaction enabled by transfer dehydrogenation (TD). This catalytic system is effective for CDA of both cyclohexanone and cyclohexanol derivatives and demonstrates excellent tolerance toward a variety of functional groups, including readily oxidizable electron-rich heterocycles. DFT studies further reveal that the (cis-P2Cl)Ir catalyst is thermodynamically disfavored for the formation of a potential out-of-cycle catalyst species, iridium phenoxyl hydride complex, via oxidative addition of the phenol O-H bond, thereby preventing catalyst inhibition observed in the previously reported TD system.

M06-2X/6-311+G** method has been used to systematically study the decomposition mechanism of nitroglycerin (NG), including unimolecular thermal decomposition, non-catalytic hydrolysis, HNO3 catalyzed hydrolysis, and decomposition involving metal salt/base impurities (combinations of Zn2+/Mg2+ cations with OH-/(NO)-N-3-/Cl-anions). Consistent with previous reports, the homolytic cleavage of the O-NO2 to generate center dot NO2 free radicals was identified as the optimal initial pathway in unimolecular decomposition. In the presence of acidic impurities, several reaction modes were explored. The optimal pathway involves proton-activated heterolytic cleavage of the O-NO2 bond in the nitrate ester group, releasing the nitronium ion (NO2+), which subsequently reacts with water to form nitric acid. The energy barrier for acid-catalyzed hydrolysis was calculated as 28.1 kcal/mol, 5.8 kcal/mol lower than the O-NO2 homolysis barrier in unimolecular decomposition, making it a more plausible mechanism for the slow room-temperature decomposition. Notably, the continuous release of HNO3 during hydrolysis creates an autocatalytic acceleration effect. For reactions of Zn(OH)(2) and moderately strong base Mg(OH)(2) with NG, the energy barriers were 25.3 and 21.3 kcal/mol, respectively. In this reaction mode, there is a cooperation effect of Lewis acid activation and the direct attack by anionic ligands on the nitrate ester, enabling relatively rapid decomposition. Although stoichiometric in nature, the generated nitric acid intermediates exhibit higher collision probabilities with NG molecules than with alkaline species for neutralization, potentially triggering acid-catalyzed decomposition. Once initiated, this acid-catalyzed process becomes self-accelerating. Zn2+ and Mg2+ nitrates/chlorides showed limited catalytic activity. We conclude that the acid-catalyzed mechanism most likely represents the true pathway for NG's gradual decomposition at ambient temperatures. Previous theoretical studies have predominantly focused on the unimolecular decomposition pathways of nitroglycerin and neglected the influence of impurities, failing to adequately account for the observed slow decomposition at ambient temperatures. Our research provides valuable references on the study of nitroglycerin.

The coupling of N-acyl-N '-substituted hydrazines with (hetero)aryl bromides and chlorides is efficiently catalyzed by CuI/4-hydroxy picolinamide and Cu(OAc)2/6-hydroxy picolinohydrazide, respectively. Under these conditions, a broad range of (hetero)aryl halides and N-acyl-N '-substituted hydrazines react smoothly at 80-120 degrees C, affording the corresponding products in good to excellent yields in most cases.

Phosphine oxides featuring P-stereogenic center are popularly used in chiral ligands, catalysts and materials. Related methods focus on the preparation of P(V) skeleton containing different types of carbon substituents for facile enantiocontrol. In comparison, phosphine oxide containing all three C(sp2)-substituents is seldom studied. Here we describe a novel protocol to achieve fully C(sp2)-substituted P(V) stereocenters via synergistic Pd/Co-catalyzed hydrophosphinylation of conjugated enynes with masked P(V) nucleophile. 1,2-Hydrophosphinylation is exclusively observed, different from prior work involving 1,4-hydrophosphinylation. A group of newly modified chiral Boxmi ligands guarantee the high stereocontrol of the transformation. Mechanistic studies suggest the outer-sphere allylic substitution as the rate-determining step.

Currently, most sulfoximine clinical candidates feature both S-aryl and S-alkyl substituents. The asymmetric synthesis of these compounds typically relies on oxidizing corresponding enantioenriched sulfilimines. Herein, we describe an effective catalytic system comprising CuI and an azabicyclo[2.2.1] carboxylic acid-derived amide ligand. This system enables the highly enantioselective coupling of S-alkyl sulfenamides with (hetero)aryl iodides to afford aryl alkyl sulfilimines. A wide range of functionalized (hetero)aryl iodides and S-alkyl sulfenamides are compatible under the reaction conditions, providing an attractive approach for assembling enantioenriched aryl alkyl sulfilimines. The utility of this method is demonstrated by the gram-scale asymmetric synthesis of clinical candidate TNG 260 and the formal asymmetric synthesis of three additional drug candidates.

Azulene is one of the few all carbon dipole molecules that is expected to achieve ferroelectricity through the superposition of molecular dipoles. Through rational analysis, four 1,3-di-tert-butylazulene derivatives were synthesized, namely 1,3-di-tert-butylazulene (1), 1,3-di-tert-butyl-6-trifluoromethylazulene (2), 1,3-di-tert-butyl-6-fluoroazulene (3), and 1,3-di-tert-butyl-5-(6'-azulene)-6-fluoroazulene (4). The single crystal structures of these compounds are Aba2, Fdd2, Pna2(1), and Cc space groups all belong to 10 polar point groups and overcome antiparallel stacking in the crystal, exhibiting macroscopic polarization. Compound 4 is stacked in a molecular dipole consistent manner. This indicates that the introduction of large steric hindrance tert-butyl groups effectively reduces intermolecular dipole-dipole interactions. Compounds 1 and 4 exhibited significant second harmonic generation (SHG) signals at 300 K, which were approximately 1/4 and 2/3 of the typical inorganic ferroelectric potassium dihydrogen phosphate (KDP). These research results indicate that fluoro-group substitution and 5-site modification on azulene units are effective strategies for obtaining azulene derivatives with 10 polar point groups, providing ideas for the development of new azulene organic ferroelectrics.

XPR1 is emerging as the only known inorganic phosphate (Pi) exporter in humans, critical for Pi homeostasis, with its activity stimulated by inositol pyrophosphate InsP8 and regulated by neuronal scaffold protein KIDINS220. Our structural studies reveal that InsP8 specifically activates XPR1 in a stepwise manner, involving profound SYG1/PHO/XPR1 (SPX) domain movements. Each XPR1 subunit functions with four gating states, in which Pi permeates a constriction site via a knock-kiss-kickprocess. By contrast, KIDINS220 delicately stabilizes XPR1 in a closed conformation through multiple mechanisms, one of which involves trapping the XPR1 alpha 1 helix-critical for InsP8 binding-within an interaction hub. InsP8 serves as a key to release KIDINS220's restraint, reinforcing a key-to-locksmechanism to safeguard the stepwise activation. Additionally, our study provides direct structural insights into XPR1-associated neuronal disorders and highlights the evolutionary conservation and divergence among XPR1 orthologs, offering a comprehensive understanding of Pi homeostasis across species.