Oxysulfonylation of Alkynes with Sodium Sulfinates to Access ß-Keto Sulfones Catalyzed by BF3·OEt2.

An efficient and operationally simple method for the synthesis of ß-keto sulfones through the BF3·OEt2-promoted reaction of alkynes and sodium sulfinates is developed. With its facile and selective access to the targets, it features good functional group compatibility, mild conditions, easily available starting materials, and good yields. Notably, the reaction does not require metal catalysts or chemical reagents with pungent odors.

Macrophage ILF3 promotes abdominal aortic aneurysm by inducing inflammatory imbalance in male mice.

Imbalance of proinflammatory and anti-inflammatory responses plays a crucial role in the progression of abdominal aortic aneurysms. ILF3, a known modulator of the innate immune response, is involved in cardiovascular diseases. This study aims to investigate the role of ILF3 in abdominal aortic aneurysm formation. Here, we use multi-omics analyzes, transgenic male mice, and multiplex immunohistochemistry to unravel the underlying involvement of ILF3 in abdominal aortic aneurysms. The results show that macrophage ILF3 deficiency attenuates abdominal aortic aneurysm progression, while elevated macrophage ILF3 exacerbates abdominal aortic aneurysm lesions. Mechanistically, we reveal that macrophagic ILF3 increases NF-κB activity by hastening the decay of p105 mRNA, leading to amplified inflammation in macrophages. Meanwhile, ILF3 represses the anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway through facilitating the ILF3/eIF4A1 complex-mediated enhancement of Keap1 translational efficiency. Moreover, Bardoxolone Methyl treatment alleviates the severity of abdominal aortic aneurysm lesions in the context of elevated ILF3 expression. Together, our findings underscore the significance of macrophage ILF3 in abdominal aortic aneurysm development and suggest its potential as a promising therapeutic target for abdominal aortic aneurysms.

C3-Alkylation of Imidazo[1,2-a]pyridines via Three-Component Aza-Friedel-Crafts Reaction Catalyzed by Y(OTf)3.

As an important class of nitrogen-containing fused heterocyclic compounds, imidazo[1,2-a]pyridines often exhibit significant biological activities, such as analgesic, anticancer, antiosteoporosis, anxiolytic, etc. Using Y(OTf)3 as a Lewis acid catalyst, a simple and efficient method has been developed for the synthesis of C3-alkylated imidazo[1,2-a]pyridines through the three-component aza-Friedel-Crafts reaction of imidazo[1,2-a]pyridines, aldehydes, and amines in the normal air atmosphere without the protection of inert gas and special requirements for anhydrous and anaerobic conditions. A series of imidazo[1,2-a]pyridine derivatives were obtained with moderate to good yields, and their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Furthermore, this conversion has the advantages of simple operation, excellent functional group tolerance, high atomic economy, broad substrate scope, and can achieve gram-level reactions. Notably, this methodology may be conveniently applied to the further design and rapid synthesis of potential biologically active imidazo[1,2-a]pyridines with multifunctional groups.

The first specific probe for pyrrolidine with multifunction by the interaction mechanism of atomic economic reaction.

Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10-6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.

Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.

Fluorinated benzothiadiazole fluorescent probe based on ICT mechanism for highly selectivity and sensitive detection of fluoride ion.

Excessive fluoride ion (F-) in the environment can affect health and even endanger life when ingested by the human body. However, most fluoride probes have the disadvantages of low sensitivity and long detection time. Herein, fluorescent probe 3a is successfully synthesized by linking two acetylenyltrimethylsilyl groups at both ends of the fluorinated benzothiadiazole core. After the addition of F- to 3a, the emission at 436 nm is significantly quenched and slightly blue-shifted. It is confirmed by electrospray ionization high-resolution mass spectrometry (ESI-HRMS) and density functional theory calculations (DFT) that these changes are due to the F- triggered Si-C bond cleavage and the subsequent inactivation of intramolecular charge transfer (ICT). The detection limit and response time of probe 3a for F- are 10-8 mol/L and 25 s, respectively. Importantly, fluorescent material 3a can be processed into portable test tools for the visual detection of fluoride ion.

Influence of the substituents of the thiol ligand on the optical properties of AuCu14.

Detailed photophysical processes of two AuCu14 clusters with different substituents (-F or -C(CH3)3) of the thiol ligand were studied in this work. The electronic effect of the substituents led to structural shrinkage, thus enhancing the luminous intensity. The internal conversion (IC) and intersystem crossing (ISC) rates in the AuCu14-C(CH3)3 crystal were slower compared with the AuCu14-F crystal, which was caused by the steric effect.

Stepwise structural evolution toward robust carboranealkynyl-protected copper nanocluster catalysts for nitrate electroreduction.

Atomically precise metal nanoclusters (NCs) are emerging as idealized model catalysts for imprecise metal nanoparticles to unveil their structure-activity relationship. However, the directional synthesis of robust metal NCs with accessible catalytic active sites remains a great challenge. In this work, we achieved bulky carboranealkynyl-protected copper NCs, the monomer Cu13·3PF6 and nido-carboranealkynyl bridged dimer Cu26·4PF6, with fair stability as well as accessible open metal sites step by step through external ligand shell modification and metal-core evolution. Both Cu13·3PF6 and Cu26·4PF6 demonstrate remarkable catalytic activity and selectivity in electrocatalytic nitrate (NO3-) reduction to NH3 reaction, with the dimer Cu26·4PF6 displaying superior performance. The mechanism of this catalytic reaction was elucidated through theoretical computations in conjunction with in situ FTIR spectra. This study not only provides strategies for accessing desired copper NC catalysts but also establishes a platform to uncover the structure-activity relationship of copper NCs.

Discovery of novel coumarin-based KRAS-G12C inhibitors from virtual screening and Rational structural optimization.

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.

Boosting 2000-Fold Hypergolic Ignition Rate of Carborane by Substitutes Migration in Metal Clusters.

Hypergolic propellants rely on fuel and oxidizer that spontaneously ignite upon contact, which fulfill a wide variety of mission roles in launch vehicles and spacecraft. Energy-rich carboranes are promising hypergolic fuels, but triggering their energy release is quite difficult because of their ultrastable aromatic cage structure. To steer the development of carborane-based high-performance hypergolic material, carboranylthiolated compounds integrated with atomically precise copper clusters are presented, yielding two distinct isomers, Cu14B-S and Cu14C-S, both possessing similar ligands and core structures. With the migration of thiolate groups from carbon atoms to boron atoms, the ignition delay (ID) time shortened from 6870 to 3 ms when contacted with environmentally benign oxidizer high-test peroxide (HTP, with a H2O2 concentration of 90%). The extraordinarily short ignition ID time of Cu14B-S is ranking among the best of HTP-active hypergolic materials. The experimental and theoretical findings reveal that benefitting from the migration of thiolate groups, Cu14B-S, characterized by an electron-rich metal kernel, displays enhanced reducibility and superior charge transfer efficiency. This results in exceptional activation rates with HTP, consequently inducing carborane combustion and the simultaneous release of energy. This fundamental investigation shed light on the development of advanced green hypergolic propulsion systems.

A reactive compatibilization with the compound containing four epoxy groups for polylactic acid/poly(butylene adipate-co-terephthalate)/thermoplastic starch ternary bio-composites.

How to effectively improve the poor interfacial adhesion between polylactic acid/poly(butylene adipate-co-terephthalate) (PLA/PBAT) matrix and thermoplastic starch (TPS) is still a challenge. Therefore, this work aims to introduce a convenient method to enhance the performance of PLA/PBAT/TPS blend by melt reactive extrusion. Here, using 4,4'-methylene-bis(N,N-diglycidyl-aniline) (MBDG) containing four epoxy groups as a reactive compatibilizer, and respectively using 1-methylimidazole (MI) or triethylenediamine (TD) as a catalyzer, serial PLA/PBAT/TPS ternary bio-composites are successfully prepared via melt reactive extrusion. The results showed that, under the catalysis of organic base, especially MI, the epoxy groups of MBDG can effectively react with hydroxyl and carboxyl groups of PLA/PBAT and hydroxyl groups in TPS to form chain-expanded and cross-linked structures. The tensile strength of the composites is increased by 20.0 % from 21.1 MPa, and the elongation at break is increased by 182.4 % from 17.6 % owing to the chain extension and the forming of cross-linked structures. The molecular weight, thermal stability, crystallinity, and surface hydrophobicity of the materials are gradually improved with the increase of MBDG content. The melt fluidity of the composites is also improved due to the enhancement of compatibility. The obtained PLA/PBAT/TPS materials have the potential to be green plastic products with good properties.

Thiacalix[4]arene Etching of an Anisotropic Cu70H22 Intermediate for Accessing Robust Modularly Assembled Copper Nanoclusters.

Atom-precise metal nanoclusters (NCs) with large bulk (nuclearity >60) are important species for insight into the embryonic phase of metal nanoparticles and their top-down etching synthesis. Herein, we report a metastable rod-shaped 70-nuclei copper-hydride NC, [Cl@Cu70H22(PhC≡C)29(CF3COO)16]2+ (Cu70), with Cl- as the template, in which the Cl@Cu59 kernel adopts a distinctive metal packing mode along the bipolar direction, and the protective ligand shell exhibits corresponding site differentiation. In terms of metal nuclearity, Cu70 is the largest alkynyl-stabilized Cu-hydride cluster to date. As a typical highly active intermediate, Cu70 could undergo a transformation into a series of robust modularly assembled Cu clusters (B-type Cu8, A-A-type Cu22, A-B-type Cu23, and A-B-A-type Cu38) upon etching by p-tert-butylthiacalix[4]arene (H4TC4A), which could not be achieved by "one-pot" synthetic methods. Notably, the patterns of A and B blocks in the Cu NCs could be effectively modulated by employing appropriate counterions and blockers, and the modular assembly mechanism was illustrated through comprehensive solution chemistry analysis using HR-ESI-MS. Furthermore, catalytic investigations reveal that Cu38 could serve as a highly efficient catalyst for the cycloaddition of propargylic amines with CO2 under mild conditions. This work not only enriched the family of high-nuclear copper-hydride NCs but also provided new insights into the growth mechanism of metal NCs.

Highly Efficient Stable Luminescent Radical-Based X-ray Scintillator.

Stable luminescent radicals are open-shell emitters with unique doublet emission characteristics. This feature makes stable luminescent radicals exhibit widespread application prospects in constructing optical, electrical, and magnetic materials. In this work, a stable luminescent radical-based X-ray scintillator of AuPP-1.0 was prepared, which exhibited a high X-ray excited luminescence (XEL) efficiency as well as excellent stability. A mechanism study showed that the heavy atom of Au in AuPP-1.0 endowed it with effective absorption of X-rays, and the doublet emission characteristics of AuPP-1.0 significantly increased its exciton utilization rate in the radioluminescence process. Moreover, AuPP-1.0 has good processability to fabricate a flexible screen for high-quality X-ray imaging, whose resolution can reach 20 LP mm-1. This work demonstrates that the doublet emission is beneficial for improving the exciton utilization rate of radioluminescence, providing a brand-new strategy for the construction of high-performance X-ray scintillators.

Trace water in a BF3·OEt2 system: a facile access to sulfinyl alkenylsulfones from alkynes and sodium sulfinates.

A highly efficient and operationally simple method for the synthesis of ß-sulfinyl alkenylsulfones through a BF3·OEt2-promoted reaction of alkynes and sodium sulfinates is developed, successfully avoiding the complicated anhydrous treatment before the reaction and greatly simplifying the reaction conditions. As a facile and selective route to the targets, it features good functional group compatibility, mild conditions, easily available starting materials, and excellent yields. Notably, the trace water in solvent plays a key role in promoting the reaction, which provides a more practical pathway for the utilization of the BF3·OEt2 catalytic system.

DBDMH-Promoted Methylthiolation in DMSO: A Metal-Free Protocol to Methyl Sulfur Compounds with Multifunctional Groups.

Organic thioethers play an important role in the discovery of drugs and natural products. However, the green synthesis of organic sulfide compounds remains a challenging task. The convenient and efficient synthesis of 5-alkoxy-3-halo-4-methylthio-2(5H)-furanones from DMSO is performed via the mediation of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), affording a facile route for the sulfur-functionalization of 3,4-dihalo-2(5H)-furanones under transition metal-free conditions. This new approach has demonstrated the functionalization of non-aromatic Csp2-X-type halides with unique structures containing C-X, C-O, C=O and C=C bonds. Compared with traditional synthesis methods using transition metal catalysts with ligands, this reaction has many advantages, such as the lower temperature, the shorter reaction time, the wide substrate range and good functional group tolerance. Notably, DMSO plays multiple roles, and is simultaneously used as an odorless methylthiolating reagent and safe solvent.

1927nm fractional thulium fiber laser combined with 30% salicylic acid for the treatment of acne and acne scars: A prospective, randomized, and split-face study.

OBJECTIVES: Patients with acne usually develops acne scars subsequently, early intervention of scars is crucial in acne management. 1927nm fractional thulium fiber laser (TFL) is effective in scars improvement and chemical peels with 30% supramolecular salicylic acid (SSA) can be applied for the treatment of acne. The purpose of this study is to evaluate and compare the efficacy and safety of TFL monotherapy versus the concomitant application of TFL and 30% SSA on acne and acne scars. MATERIALS AND METHODS: Thirty-three patients with acne and acne scars were enrolled, and two sides of the face were randomly divided to receive either TFL and SSA chemical peeling or TFL. Four sessions of TFL treatments were applied with 4-week intervals for both sides, SSA combined treatment side received eight SSA chemical peels with 2-week intervals additionally. GAGS, ECCA score, the number of acne lesions, melanin index (MI) and erythema index (EI), transepidermal water loss (TEWL), and side effects were recorded at Weeks 0, 4, 8, 12, and 18. Satisfaction of patients was recorded on both sides at the end of the study. RESULTS: Thirty patients completed the study. Both control group (TFL monotherapy) and SSA group (TFL combined with SSA chemical peeling) significantly improved GAGS and ECCA score. SSA group showed higher efficacy in terms of GAGS and ECCA score, acne lesion count, TEWL, MI, EI, and satisfaction than control group. All the side effects were temporary and tolerable, no adverse effects were observed. CONCLUSIONS: Both TFL and the TFL combined with 30% SSA chemical peeling are safe and effective for the treatment and prevention of acne and acne scars, though the combined group has higher efficacy.

Fine-tuning benzazole-based probe for the ultrasensitive detection of Hg2+ in water samples and seaweed samples.

Developing potentially toxic metal ion probes is significant for environment and food safety. Although Hg2+ probes have been extensively studied, small molecule fluorophores that can integrate two applications of visual detection and separation into one unit remain challenging to access. Herein, by incorporating triphenylamine (TPA) into tridentate skeleton with an acetylene bridge, 2,6-bisbenzimidazolpyridine-TPA (4a), 2,6-bisbenzothiazolylpyridine-TPA (4b) and 2,6-bisbenzothiazolylpyridine-TPA (4c) were first constructed, expectably showing distinct solvatochromism and dual-state emission properties. Since the diverse emission properties, the fluorescence detection of 4a-4b can be achieved with an ultrasensitive response (LOD = 10-11 M) and efficient removal of Hg2+. More interestingly, 4a-4b can not only be developed into paper/film sensing platform, but also reliably detect Hg2+ in real water and seaweed samples, with recoveries ranging from 97.3% to 107.8% and a relative standard deviation of less than 5%, indicating that they have excellent application potential in the field of environmental and food chemistry.

Thermally Activated Delayed Fluorescence Coinage Metal Cluster Scintillator.

X-ray scintillators are widely used in medical imaging, industrial flaw detection, security inspection, and space exploration. However, traditional commercial scintillators are usually associated with a high use cost because of their substantial toxicity and easy deliquescence. In this work, an atomically precise Au-Cu cluster scintillator (1) with a thermally activated delayed fluorescence (TADF) property was facilely synthesized, which is environmentally friendly and highly stable to water and oxygen. The TADF property of 1 endows it with an ultrahigh exciton utilization rate. Combined with the effective absorption of X-ray caused by the heavy-atom effect and a limited nonradiative transition caused by close packing in the crystal state, 1 exhibits an excellent radioluminescence property. Moreover, 1 has good processability for fabricating a large, flexible thin-film device (10 cm × 10 cm) for high-resolution X-ray imaging, which can reach 40 µm (12.5 LP mm-1). The properties mentioned earlier make the coinage metal cluster promising for use as a substitute for traditional commercial scintillators.

Regulating structural asymmetry via fluorination engineering in hybrid lead bromide perovskites.

Here, we synthesized a pair of chiral two-dimensional lead bromide perovskites R-/S-(C3H7NF3)2PbBr4 (1R/2S) using a H/F substitution strategy, which exhibit circular dichroism (CD) and circularly polarized luminescence (CPL) activity. Compared with one-dimensional non-centrosymmetric (C3H10N)3PbBr5 with local asymmetry obtained by isopropylamine, 1R/2S show a centrosymmetric inorganic layer despite the global chiral space group. Density functional theory calculations show that the formation energy of 1R/2S is lower than that of (C3H10N)3PbBr5, which implies the improved moisture stability in photophysical properties and CPL activity.

High Performance Dynamic X-ray Flexible Imaging Realized Using a Copper Iodide Cluster-Based MOF Microcrystal Scintillator.

X-ray imaging technology has achieved important applications in many fields and has attracted extensive attentions. Dynamic X-ray flexible imaging for the real-time observation of the internal structure of complex materials is the most challenging type of X-ray imaging technology, which requires high-performance X-ray scintillators with high X-ray excited luminescence (XEL) efficiency as well as excellent processibility and stability. Here, a macrocyclic bridging ligand with aggregation-induced emission (AIE) feature was introduced for constructing a copper iodide cluster-based metal-organic framework (MOF) scintillator. This strategy endows the scintillator with high XEL efficiency and excellent chemical stability. Moreover, a regular rod-like microcrystal was prepared through the addition of polyvinyl pyrrolidone during the in situ synthesis process, which further enhanced the XEL and processibility of the scintillator. The microcrystal was used for the preparation of a scintillator screen with excellent flexibility and stability, which can be used for high-performance X-ray imaging in extremely humid environments. Furthermore, dynamic X-ray flexible imaging was realized for the first time. The internal structure of flexible objects was observed in real time with an ultrahigh resolution of 20 LP mm-1 .