Most of the reported work focus on the development of O-, N-, C- and S-glycosylation methods. However, no study explores P(III)-glycosylation reaction. Herein we describe a convenient protocol to realize P(III)-glycosylation process. A simple beta-phosphino ester is adopted as P(III)-transfer reagent for this new type of glycosylation via a nucleophilic substitution and release strategy. Diverse phosphine units are introduced to the anomeric center of various sugars efficiently and with excellent stereoselectivity. The value of this method is showcased by the prepared P(III)-sugars as novel linkers in bioactive molecule conjugation, new chiral ligands in metal-catalyzed asymmetric allylic substitutions and organocatalysts. Preliminary mechanistic studies corroborated the designed P(III)-transfer process.

Rhodium-catalyzed regio- and enantioselective allylic arylation of racemic alkyl- and aryl- substituted allylic carbonates with arylboronic acids using commercially available BIBOP ligand is reported. This reaction proceeds at room temperature without base or other additive to deliver allylic arylation products in excellent yields, regio- and enantioselectivity (up to 95% yield, >20:1 b/l, >99% ee). Rh/BIBOP is disclosed as an efficient catalytic system for allylic substitution reaction.

The cycloaddition reactions of bicyclo[1.1.0]butanes with alkenes, imines, nitrones, or aziridines have served as an efficient platform to create conformationally restricted saturated bicyclic scaffolds. However, the use of readily available aromatics in such reactions, especially in an asymmetric manner, remains underexplored. Herein, we report a highly regio- and enantioselective dearomative [2 pi + 2 sigma] photocycloaddition reaction between naphthalene derivatives and bicyclo[1.1.0]butanes, enabled by Gd(III) catalysis. Bicyclo[1.1.0]butanes and naphthalenes adorned with a diverse array of functional groups are well-tolerated under mild conditions, affording enantioenriched pharmaceutically important bicyclo[2.1.1]hexanes in 30-96% yields with 81-93% ee and 12:1 -> >20:1 rr. The synthetic versatility of this reaction is further demonstrated by the facile removal of directing group and derivatizations of the dearomatized product. UV-vis absorption spectroscopy studies suggest the involvement of an excited naphthalene species in the reaction process.

Fluoroether approach has been extensively employed as an alternative to conventional fluorinated surfactants; however, it faces challenges such as inadequate performance of short fluoroether chains and environmental contamination from long fluoroether chains. This study aims to address the conflict between environmental compatibility and the performance of fluoroether surfactants. The design of the surfactants is centered around the OC chain (CF3(OCF2) n -), utilizing reduced fluorine content to achieve superior surface activity. A series of surfactant molecules featuring elongated hydrophobic chains and dual-chain structures have been synthesized and characterized. All of the molecules have good surface activity at low concentrations. Among them, CF3(OCF2)4CH2O(CH2)3SO2NH(CH2)3N+(CH3)2CH2COO- (OC4F-B), which employs a strategy of extending the hydrophobic chain by insertion of -CH2O(CH2)3-, shows the best performance. This surfactant can achieve a surface tension of 20 mN/m at a concentration of 0.005 wt %, which is 20 times lower than that required for CF3(OCF2)4CONH(CH2)3N+(CH3)2CH2COO- (OC4-betaine) to attain the same surface tension. In contrast, (CF3(OCF2)3CH2O(CH2)3SO2NHCH2CH2)2N+(CH3)CH2COO- (DOC3F-B), utilizing both dual-chain and extended carbon chain strategies, exhibits a critical micelle concentration that is diminished by 2 orders of magnitude relative to OC3-betaine, reaching to 0.047 g/L. Merely adjusting the length of the fluorocarbon chain is insufficient to reconcile the conflict between the performance and environmental impact of fluorinated surfactants. This study introduces an innovative approach by incorporating hydrocarbon hydrophobic chains and adopting a dual-chain design, thereby addressing this challenge effectively.

A cerium ammonium nitrate (CAN)-promoted C(sp2)-N coupling reaction of secondary amides with aryl boronic acids has been realized, providing a new entry for the construction of structurally diverse tertiary aryl amides, which are widely found in various biologically active molecules. Preliminary mechanistic studies indicated that a radical pathway may be involved in the C(sp2)-N coupling process. Compared with other metal-catalyzed methods, which in some cases require well-designed catalysts, preassembled directing groups, and/or complicated operations, this methodology features a ligand- and directing group-free process, as well as ease of handling.

Aflatoxin B1 (AFB1), a highly toxic secondary metabolite produced by Aspergillus species, represents a significant health hazard due to its widespread contamination of agricultural products. The urgent need for sensitive and sustainable detection methods has driven the development of diverse analytical approaches, most of which heavily rely on organic solvents, posing environmental challenges for routine food safety analysis. Here, we introduce a supramolecular platform leveraging acyclic cucurbit[n]uril (acCB) as a host molecule for environmentally sustainable AFB1 detection. Screening various acCB derivatives identified acCB6 as a superior host capable of forming a stable 1:1 complex with AFB1 in an aqueous solution, exhibiting a high binding affinity. Proton nuclear magnetic resonance (1H NMR) spectroscopy confirmed that AFB1 was deeply encapsulated within the host cavity, with isothermal titration calorimetry (ITC) experiments and molecular dynamics simulations further substantiating the stability of the interaction, driven by enthalpic and entropic contributions. This supramolecular host was incorporated into a scaffold-assembly-based bioluminescent enzyme immunoassay (SA-BLEIA), providing a green detection platform that rivals the performance of traditional organic solvent-based assays. Our findings highlight the potential of supramolecular chemistry as a foundation for eco-friendly mycotoxin detection and offer valuable insights into designing environmentally sustainable analytical methods.

In this study, an electrocatalytic tandem cyclization reaction of amide-tethered methylenecyclopropanes has been developed, which can realize the rapid construction of tetracyclic benzazepine derivatives in moderate yields with good functional group compatibility under relatively mild conditions. In this transformation, the catalytic amount of ferrocene serves as the electrocatalytic medium, and electron transfer on electrodes can replace oxidants or reducing agents, which is more environmentally friendly than and economically comparable to traditional photocatalysis or metal catalysis. Moreover, the origin of the regiochemistry is well elucidated through density functional theory (DFT) calculations.

Ubiquitination plays vital roles in modulating pathogen-host cell interactions. RNF213, a E3 ligase, can catalyze the ubiquitination of lipopolysaccharide (LPS) and is crucial for antibacterial immunity in mammals. Shigella flexneri, an LPS-containing pathogenic bacterium, has developed mechanisms to evade host antibacterial defenses during infection. However, the precise strategies by which S. flexneri circumvents RNF213-mediated antibacterial immunity remain poorly understood. Here, through comprehensive biochemical, structural and cellular analyses, we reveal that the E3 effector IpaH1.4 of S. flexneri can directly target human RNF213 via a specific interaction between the IpaH1.4 LRR domain and the RING domain of RNF213, and mediate the ubiquitination and proteasomal degradation of RNF213 in cells. Furthermore, we determine the cryo-EM structure of human RNF213 and the crystal structure of the IpaH1.4 LRR/RNF213 RING complex, elucidating the molecular mechanism underlying the specific recognition of RNF213 by IpaH1.4. Finally, our cell based functional assays demonstrate that the targeting of host RNF213 by IpaH1.4 promotes S. flexneri proliferation within infected cells. In summary, our work uncovers an unprecedented strategy employed by S. flexneri to subvert the key host immune factor RNF213, thereby facilitating bacterial proliferation during invasion.

Highly emissive metallacages that generate reactive oxygen species (ROS) are important to synergistic cancer therapy, but it is still challenging to balance the emission and phototheranostic properties. Herein, a metallacage of DTPABT-Mc is prepared. It is observed that emission in the near-infrared region from 600 to 1000 nm with a high photoluminescence quantum yield value of 7.92% in solids is recorded for DTPABT-Mc. In addition, the ability to produce both type I and type II ROS under light irradiation is also observed, leading to potential application in photodynamic therapy (PDT) and chemotherapy. After that, 4T1@DTPABT-Mc-NPs, covering DTPABT-Mc nanoparticles with 4T1 cell membranes, are prepared to enhance their tumor-targeting ability. This finally results in effective therapeutic performance in vivo, effectively inhibiting tumor growth. These results suggest that DTPABT-Mc-NPs exhibit excellent synergistic therapeutic effects by combining PDT and chemotherapy, providing new ideas to design agents for diagnosis and therapy in the future.

Rapid and highly frequent measurements of exhaled breath hold significant value for disease diagnosis and exposure assessments. Direct inlet mass spectrometry and ion mobility spectrometry demonstrate great potential for on-site breath analysis, but their accuracy and sensitivity are notably affected by the high humidity in the breath samples. A miniature and continuous dehydration device based on dual-switching thermoelectric cold traps has been developed to efficiently reduce the humidity of breath gas from saturation to relative humidity of 4.3%, and a subcooling compensation method was adopted to eliminate the humidity fluctuations when switching the two cold traps to remove the condensed water in the trap, which could achieve a stable outlet humidity with RSD of 8.2% regardless of inlet humidity variations. The performance and profits of the miniature dehydration device for on-site analysis of breath samples have been tested by coupling with direct inlet photoionization ion mobility spectrometry and time-of-flight mass spectrometry. Trace breath acetone could be directly measured, and its concentration profiles over an 8 h period in fasting volunteers could be continuously monitored every 30 s. Furthermore, the m/z peaks from chlorinated hydrocarbons in exhaled breath samples were clearly identified after passing the dehydration device, which can be used for an occupational health assessment of the widely used halocarbon solvents.

A modular approach to the potent, broad-spectrum antibiotic amycolamicin and seven diastereomeric analogues is described. The synthesis features bioinspired construction of the high-carbon amycolose segment, gold(I)-catalyzed high-yielding O-glycosylation of the trans-decalin scaffold, N-glycosylation of the bromoacetylated l-valine derivative, and condition-tuned late-stage C-acylation of the tetramic acid motif. An assessment of the antibacterial properties of these synthetic molecules indicated that the correct stereochemistry is essential for the potent bioactivity of amycolamicin.

Mono-metallic catalysts dominate in homogeneous catalysis, wherein all the element steps generally occur on one metal site. Inspired from bimetallic active sites in both enzymes and heterogeneous catalysts, the development of binuclear catalysis can offer the potential to induce novel intermediates, reactivity, and selectivity. Metal-catalyzed hydroarylation of alkynes generally leads to one alkyne incorporated products and alkyne dimerization-hydrocarbofunctionalization is rather challenging via conventional mono-metallic intermediates. Herein, a highly selective dimerization-hydrocarbofunctionalization of internal alkynes is achieved via dinickel catalysis, leading to the formation of synthetically challenging pentasubstituted 1,3-dienes. Mechanistic studies suggest that each Ni site can promote distinct elementary steps of two alkynes to generate a di-vinyl di-Ni intermediate. Such a mode of binuclear convergent catalysis is fundamentally different from the traditional mono-metallic catalysis and may provide new understanding on binuclear synergistic effects at atomic and molecular level.

Aldo-keto reductase 1C3 (AKR1C3) plays a key role in tumor progression and chemotherapy resistance, particularly in sorafenib-resistant hepatocellular carcinoma (HCC). Targeting AKR1C3 represents a promising strategy to restore chemosensitivity in resistant HCC. Previous research identified the lead compound S07-2005 through a cascade virtual screening approach (AKR1C3 IC50 = 130 +/- 30 nM, SI (selective index) > 77). Using cocrystal-guided drug design, 30 was optimized to adopt an L-shaped conformation targeting AKR1C3 ' s subpocket 1 (SP1) and oxyanion site (OS), enhancing inhibitory potency and selectivity (AKR1C3 IC50 = 5 +/- 1 nM, SI > 2000). It enhanced sorafenib-induced ROS generation, promoted apoptosis, and restored sorafenib sensitivity in HCC models. In combination with sorafenib, compound 30 restored sorafenib sensitivity in HCC both in vitro and in vivo. Additionally, compound 30 demonstrated a favorable safety profile and pharmacokinetic properties, suggesting its potential as an adjunct to overcome AKR1C3-mediated chemotherapy resistance in cancer treatment