A novel Brφnsted acid task specific ionic liquid 1-ethylbenzimidazolium tetrafluoroborate （[Hebim]BF4） with functional benzimidazolium cation was synthesized and characterized by ^1H NMR, IR, MS spectra and element...A novel Brφnsted acid task specific ionic liquid 1-ethylbenzimidazolium tetrafluoroborate （[Hebim]BF4） with functional benzimidazolium cation was synthesized and characterized by ^1H NMR, IR, MS spectra and elemental analysis. This novel ionic liquid was successfully used as dual solvent-catalyst for the synthesis of arylic esters. Higher yields were obtained in the presence of [Hebim]BF4 in comparison with other imidazolium ionic liquids because of the good solubility of the aromatic alcohols and aromatic carboxylic acids in [Hebim]BF4. The product could be separated conveniently from the reaction system, and the ionic liquid could be easily reused after removal of water under vacuum. After 10 times reuse, the selectivity of the ester was still 100%.展开更多
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℃to give a series of biarylsulfones in 53%~96%y...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℃to give a series of biarylsulfones in 53%~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.展开更多
Lignin pyrolysis leads to the formation of diverse phenolic products that bear structural similarities to natural lignin,and the related mechanism has been widely explored based on the linkage cleavageinvolved reactio...Lignin pyrolysis leads to the formation of diverse phenolic products that bear structural similarities to natural lignin,and the related mechanism has been widely explored based on the linkage cleavageinvolved reactions.However,some unusual pyrolytic products exhibiting significant structure deviations from lignin,such as aldehydes,remain obscure in mechanism due to long-standing neglect of their formation pathways.The present work found the pivotal role of aryl migration,a special radical-mediated rearrangement process,in governing the formation of these atypical products for the first time.Herein,density functional theory calculations,electronic structure analyses,and pyrolysis experiments were combined to investigate rearrangement patterns and prerequisite structural characteristics of aryl migration by employing typical radicals derived from linkages and substituents of lignin as models.The results indicate that the radical with an unpaired electron located on the second atom of the aromatic side chain can undergo three-membered aryl 1,2-migration triggered by exo cyclization with the best superiority,determining the generation of aldehydes,alkenes,and other products through subsequent cleavage reactions.A clear correlation among the initial geometric and electronic structures of lignin,the patterns and types of aryl migration,the energy barriers,and the end products was established.This study contributes to systematically elucidating rearrangement mechanisms and constructing a more comprehensive lignin pyrolysis mechanism network.展开更多
We herein present an efficient denitrative iodination method of(hetero)nitroarenes mediated by commercially available and cost-effective hydroiodic acid(HI).During the reaction process,HI plays its dual roles as both ...We herein present an efficient denitrative iodination method of(hetero)nitroarenes mediated by commercially available and cost-effective hydroiodic acid(HI).During the reaction process,HI plays its dual roles as both the sustainable reductant of nitro group and iodine source in the iodination step,which successfully integrates three steps into a one-pot procedure and significantly simplifies the reaction system.This approach enables a smooth metal-free conversion of nitroarenes to corresponding aryl iodides via one-pot process,exhibits a broad substrate scope and good reaction efficiency,and was conveniently applied in the concise synthesis of pharmaceuticals.展开更多
The valorization of nitrous oxide(N_(2)O)as an oxygen atom donor presents an attractive opportunity for green chemistry applications,leveraging both its industrial abundance and thermodynamically favorable oxidation p...The valorization of nitrous oxide(N_(2)O)as an oxygen atom donor presents an attractive opportunity for green chemistry applications,leveraging both its industrial abundance and thermodynamically favorable oxidation potential.However,practical implementation has been constrained by the inherent kinetic inertness and poor coordinating ability of N_(2)O.While prior studies achieved N_(2)O-mediated conversion of aryl halides to phenols,such transformations necessitated stoichiometric chemical reductants and elevated pressure(2 atm),posing challenges in operational safety and process scalability.This study focuses on an electrochemical strategy that enables efficient oxygen atom transfer under ambient pressure through controlled current application.This methodology facilitates the selective transformation of aryl iodides to phenols without external reducing agents,establishing an environmentally benign synthetic pathway.By replacing traditional chemical reductants with electrons as the sole reducing equivalent,our approach addresses critical sustainability challenges in aromatic oxygenation chemistry while maintaining operational simplicity under mild conditions.展开更多
BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing int...BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.展开更多
In this work, we put forward a new and universal approach, i.e., cyanine ketone method, for fabricating meso–aryl heptamethine indocyanines, which is so simple that the treatment of the easy-to-get cyanine ketones wi...In this work, we put forward a new and universal approach, i.e., cyanine ketone method, for fabricating meso–aryl heptamethine indocyanines, which is so simple that the treatment of the easy-to-get cyanine ketones with various aromatic lithium(Ar Li), followed by acidification, could straightforwardly give rise to the products in one-pot way. Importantly, due to the strong nucleophilicity of Ar Li, a series of bulky hydrophilic aromatic groups can be facilely integrated into the meso–position of heptamethine indocyanines, not only effectively inhibiting the undesired dye self-aggregation but also largely improving the water-solubility. Using one of anti-aggregation meso–aryl heptamethine indocyanines, we fabricated a dye-antibody conjugate for in vivo imaging tumor in a mouse model and achieved a high tumor-tonormal tissue ratio. The work laid a chemical foundation for constructing various meso–aryl heptamethine indocyanines, facilitating the advanced imaging and therapeutic applications in future.展开更多
The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty ...The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.展开更多
Herein,a metal-free electrochemical demethoxyl-cyanation of methoxyarenes via aromatic nucleophilic substitution(S_(N)Ar) using TMSCN as a cheap cyanide source under mild conditions has been presented.This transformat...Herein,a metal-free electrochemical demethoxyl-cyanation of methoxyarenes via aromatic nucleophilic substitution(S_(N)Ar) using TMSCN as a cheap cyanide source under mild conditions has been presented.This transformation utilizes commercially available reagents,cheap electrodes,and simple equipment.Diverse aryl nitriles were successfully obtained in a direct and efficient way with broad substrate scope,excellent functional group tolerance,and selective C-O bond cleavage.Furthermore,late-stage modification of biorelevant compounds and gram-scale synthesis highlighted the potential application of the strategy.Mechanistic investigations suggest that the arene cation radical was considered as the key intermediate for the transformation,and undergoing the followed S_(N)Ar process.展开更多
The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran so...The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran sodium sulfate.Several Lactobacillus strains isolated from the healthy human fecal sample was found to utilize Trp to produce indole derivatives.The results of Trp metabolism indicated that the ability of Lactobacillus to metabolize Trp to produce indole-3-lactic acid(ILA),indole-3-carboxaldehyde(I3C),and indole-3-acetic acid varies in vitro and in vivo.The effect of Lactobacillus with high-yielding indole derivatives on disease activity index,colon length,and intestinal permeability was significantly better than that of Lactobacillus with low-yielding indole derivatives in a high Trp diet.And Lactobacillus combined with Trp intervention also had a certain regulatory effect on the intestinal flora of male BALB/c mice.Among them,Lactiplantibacillus plantarum DPUL-S164 produced more ILA both in vivo and in vitro,and the combination of L.plantarum DPUL-S164 and Trp significantly decreased the expression level of the serum pro-inflammatory cytokine interleukin(IL)-6 and increased the expression level of the anti-inflammatory cytokine IL-10,significantly improved the number of goblet cells in the mouse mucous layer and increased mucin and tight junction protein expression.Furthermore,L.plantarum DPUL-S164 combined with Trp intervention activated the aryl hydrocarbon receptors(Ah R)signaling pathway.Furthermore,we found that the expression of colonic tight junction protein was positively correlated with the expression of colonic Ah R,and the expression of Ah R was positively correlated with the concentrations of ILA and I3C in vivo.Therefore,we conclude that the ILA as Ah R ligand produced by L.plantarum DPUL-S164 regulated the Ah R pathway,thus up-regulating the expression of the tight junction protein and protecting the integrity of the epithelial barrier.展开更多
The influence of the electronic and steric properties of bromoaromatic substrates on direct arylation polymerization for synthesizing high-molecular-weight conjugated polymers was investigated through a combination of...The influence of the electronic and steric properties of bromoaromatic substrates on direct arylation polymerization for synthesizing high-molecular-weight conjugated polymers was investigated through a combination of experiments and calculations.Bromo-aromatic substrates with electron-withdrawing fluoro substituents exhibited higher yields and degrees of polymerization under PPh3-assisted conditions compared to those with electron-donating or bulky methyl substituents.Additionally,excessive steric hindrance at ortho-sites or overly electrondeficient dibromoaromatic substrates leads to reaction inactivation.Calculations indicated that electron-withdrawing substituents enhanced the electrophilicity of arylpalladium-PPh3intermediates,facilitating the activation of electron-rich arylative substrates and promoting polymer growth.Furthermore,steric hindrance from the substituents can influence the preferred reaction pathway,thereby increasing the real reaction barriers.Both experimental and computational results suggest that bromoaromatic substrates with optimized electron-deficient characteristics significantly improve monomer conversion and polymerization efficiency with n-hexylmethylether-substituted EDOT.These findings clarify how the electronic and steric properties of bromo-aromatic substrates affect EDOT derivative activation and are expected to aid in optimizing the polymerization conditions for the preparation of high-molecular-weight conjugated polymers.展开更多
The asymmetric conjugate additions of aryl Grignard reagents to trisubstituted enones by chiral P,N ligand L6 with low catalyst loading(0.25–1.0 mol%)are disclosed.Chiral 2-ester chromanone and its analogs bearing a ...The asymmetric conjugate additions of aryl Grignard reagents to trisubstituted enones by chiral P,N ligand L6 with low catalyst loading(0.25–1.0 mol%)are disclosed.Chiral 2-ester chromanone and its analogs bearing a quaternary stereogenic centers at C2 position were produced in high to excellent yields,enantioselectivities and high turnover number.The notable features of this reaction include its broad substrate scope,complete 1,4-addition regioselectivities,applicability to both batch and flow for large scale synthesis.This report develops an efficient strategy to apply aryl Grignard reagents in asymmetric 1,4-conjugation reactions and provides a direct method to incorporate quaternary chiral centers toward the synthesis of biologically relevant chromanone derivatives.展开更多
An efficient and novel approach is proposed for oxidative arylation of bio-based furfuryl alcohol(FA)to aryl furans(AFs),a versatile monomer of photoelectric materials,in the presence of UiO-67-Pd(F)with phenanthrolin...An efficient and novel approach is proposed for oxidative arylation of bio-based furfuryl alcohol(FA)to aryl furans(AFs),a versatile monomer of photoelectric materials,in the presence of UiO-67-Pd(F)with phenanthroline/bipyridine,and poly-F substituted phenyl ligands as the mixture linkers.The results of control experiments and theoretical calculations reveal that the–F on the phenyl linkers efficiently tunes the electron-deficient nature of Pd through the Zr_(6) clusters bridges,which favors the adsorption and activation of the furan ring.Furthermore,the conjugation of different nitrogen-containing ligands facilitates Pd coordination for the Heck-type insertion and subsequent electrophilic palladation,respectively.As a result,the oxidative arylation of FA derivatives is substantially enhanced because of these electronic and steric synergistic effects.Under the optimized conditions,72.2%FA conversion and 74.8%mono aryl furan(MAF)selectivity are shown in the Heck-type insertion.Meanwhile,85.3%of MAF is converted,affording 74.8%selectivity of final product(AFs)in the subsequent electrophilic palladation reaction.This process efficiency is remarkably higher than that with homogeneous catalysts.In addition,furan-benzene polymer obtained from the halogen-free synthesis catalyzed by UiO-67-Pd(F)show significantly better properties than that from conventional Suzuki coupling method.Therefore,the present work provides a new insight for useful AFs synthesis by oxidative arylation of bio-furan via rational tunning the metal center micro-environment of heterogeneous catalyst.展开更多
Chiral aryl cyclohex-3-en ether scaffold is widely present in bioactive natural products and drugs.The exploitation of efficient and enantioselective methods for the construction of aryl cyclohex-3-en ether scaffold i...Chiral aryl cyclohex-3-en ether scaffold is widely present in bioactive natural products and drugs.The exploitation of efficient and enantioselective methods for the construction of aryl cyclohex-3-en ether scaffold is significant.Herein we disclose a chiral N,N’-dioxide/Lewis acid complex-catalyzed asymmetric inverse-electron-demand Diels-Alder(IEDDA)reaction using electron-deficient 3-carboalkoxyl-2-pyrones and less electron-enriched aryl enol ethers as reactants.A wide range of non-and 1,2-disubstituted acyclic aryl enol ethers are applicable to deliver diverse chiral bridged bicyclic lactones in high yields and stereoselectivities(up to 96%yield,>20:1 dr,97:3 er).The bridged bicyclic lactone core can be easily converted into chiral aryl cyclohex-3-en ether scaffold.Notably,DFT calculations revealed a stepwise and endo mechanism to explain the high enantioselectivity controlled by the cooperative effect of the steric factors and the dispersion interactions between ligands and enol ethers.展开更多
Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge...Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.展开更多
Covalent triazine-based frameworks（CTFs） are important microporous materials with a wide range of applications.Here,we demonstrate an environmentally benign and economic synthetic pathway to CTFs.The monomers used f...Covalent triazine-based frameworks（CTFs） are important microporous materials with a wide range of applications.Here,we demonstrate an environmentally benign and economic synthetic pathway to CTFs.The monomers used for CTFs,aromatic nitriles,were obtained by cyanation using nontoxic potassium hexacyanoferrate（Ⅱ） in place of commonly used toxic cyanides.Then,the CTFs were synthesized by trimerization of the corresponding cyano monomers in molten zinc chloride.A series of CTFs was synthesized,and the highest Brunauer-Emmett-Teller surface area measured in this series was 2404 m^2/g.Among the synthesized CTFs,CTF_（DCP） exhibited excellent CO_2 adsorption properties,with a CO_2 uptake of 225 mg/g at 0℃.展开更多
In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evalu...In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.展开更多
Although the etiology of inflammatory bowel disease is still tmcertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine （NOR）, an alkaloid isolated...Although the etiology of inflammatory bowel disease is still tmcertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine （NOR）, an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1,8 production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）. Moreover, it significantly reduced expressions of cleaved IL-lfl, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide （LPS） and adenosine triphosphate （ATP）. Furthermore, NOR could activate aryl hydrocarbon receptor （AhR） in THP-1 cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90 complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter activity and binding activity of AhR/ARNT/XRE. Both siAhR and a-naphthoflavone （a-NF） markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.展开更多
An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed.This reaction was selective to N-arylation instead of C-arylation,which provides a...An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed.This reaction was selective to N-arylation instead of C-arylation,which provides a simple synthetic method for N-aryl indoles.展开更多
A series of novel poly(aryl ether nitrile)s containing phthalazinone moiety were synthesized by the nucleophilic displacement reaction of bisphenol-like monomers(I)with 2,6-difluorobenzonitrile.The inherent viscositie...A series of novel poly(aryl ether nitrile)s containing phthalazinone moiety were synthesized by the nucleophilic displacement reaction of bisphenol-like monomers(I)with 2,6-difluorobenzonitrile.The inherent viscosities ranged from 0.46 to 1.07 dL g^-1.The glass transition temperatures were in the range of 277-295℃,and the temperatures for 10%weight loss in nitrogen atmosphere were found between 495 and 527℃.The structures of these resultant polymers were confirmed by FT-IR and 1^H NMR.Moreover,the properties of poly(aryl ether nitrile)s including solubility and crystallinity were also studied.展开更多
基金Project supported by the Key Project of Chinese Ministry of Education （No. 105075） and the National Natural Science Foundation of China （No. 20503016）.
文摘A novel Brφnsted acid task specific ionic liquid 1-ethylbenzimidazolium tetrafluoroborate （[Hebim]BF4） with functional benzimidazolium cation was synthesized and characterized by ^1H NMR, IR, MS spectra and elemental analysis. This novel ionic liquid was successfully used as dual solvent-catalyst for the synthesis of arylic esters. Higher yields were obtained in the presence of [Hebim]BF4 in comparison with other imidazolium ionic liquids because of the good solubility of the aromatic alcohols and aromatic carboxylic acids in [Hebim]BF4. The product could be separated conveniently from the reaction system, and the ionic liquid could be easily reused after removal of water under vacuum. After 10 times reuse, the selectivity of the ester was still 100%.
文摘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℃to give a series of biarylsulfones in 53%~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.
基金supported by the National Natural Science Foundation of China,China(52436009,52276189)the Postdoctoral Fellowship Program of CPSF,China(GZB20230207)the Fundamental Research Funds for the Central Universities,China(2024JC001,2024MS087)。
文摘Lignin pyrolysis leads to the formation of diverse phenolic products that bear structural similarities to natural lignin,and the related mechanism has been widely explored based on the linkage cleavageinvolved reactions.However,some unusual pyrolytic products exhibiting significant structure deviations from lignin,such as aldehydes,remain obscure in mechanism due to long-standing neglect of their formation pathways.The present work found the pivotal role of aryl migration,a special radical-mediated rearrangement process,in governing the formation of these atypical products for the first time.Herein,density functional theory calculations,electronic structure analyses,and pyrolysis experiments were combined to investigate rearrangement patterns and prerequisite structural characteristics of aryl migration by employing typical radicals derived from linkages and substituents of lignin as models.The results indicate that the radical with an unpaired electron located on the second atom of the aromatic side chain can undergo three-membered aryl 1,2-migration triggered by exo cyclization with the best superiority,determining the generation of aldehydes,alkenes,and other products through subsequent cleavage reactions.A clear correlation among the initial geometric and electronic structures of lignin,the patterns and types of aryl migration,the energy barriers,and the end products was established.This study contributes to systematically elucidating rearrangement mechanisms and constructing a more comprehensive lignin pyrolysis mechanism network.
基金the National Key Research and Development Project(No.2023YFF1205103)the National Natural Science Foundation of China(No.22371007)the Peking University Medicine plus X Pilot Program-Key Technologies R&D Project(No.2024YXXLHGG001)for financial support。
文摘We herein present an efficient denitrative iodination method of(hetero)nitroarenes mediated by commercially available and cost-effective hydroiodic acid(HI).During the reaction process,HI plays its dual roles as both the sustainable reductant of nitro group and iodine source in the iodination step,which successfully integrates three steps into a one-pot procedure and significantly simplifies the reaction system.This approach enables a smooth metal-free conversion of nitroarenes to corresponding aryl iodides via one-pot process,exhibits a broad substrate scope and good reaction efficiency,and was conveniently applied in the concise synthesis of pharmaceuticals.
基金National Natural Science Foundation of China(Project No.:52320105003,Project No.:52303019)the CAS-ANSO Co-funding Research Project(Project No.:CAS-ANSO-CF-2024)+2 种基金the National Key R&D Program of China(Project No.:2023YFC3707201)the Fundamental Research Funds for the Central Universities(Project No.:E3ET1803)China Postdoctoral Science Foundation(Project No:2024T170904)。
文摘The valorization of nitrous oxide(N_(2)O)as an oxygen atom donor presents an attractive opportunity for green chemistry applications,leveraging both its industrial abundance and thermodynamically favorable oxidation potential.However,practical implementation has been constrained by the inherent kinetic inertness and poor coordinating ability of N_(2)O.While prior studies achieved N_(2)O-mediated conversion of aryl halides to phenols,such transformations necessitated stoichiometric chemical reductants and elevated pressure(2 atm),posing challenges in operational safety and process scalability.This study focuses on an electrochemical strategy that enables efficient oxygen atom transfer under ambient pressure through controlled current application.This methodology facilitates the selective transformation of aryl iodides to phenols without external reducing agents,establishing an environmentally benign synthetic pathway.By replacing traditional chemical reductants with electrons as the sole reducing equivalent,our approach addresses critical sustainability challenges in aromatic oxygenation chemistry while maintaining operational simplicity under mild conditions.
基金Supported by the National Natural Science Foundation of China,No.81971814Pudong New Area Health Talent Training Program,No.2025PDWSYCBJ-04Shanghai’s 2023“Technology Innovation Action Plan”Medical Innovation Research Project,No.23Y11908300。
文摘BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.
基金supported by National Natural Science Foundation of China (Nos. 22277070, 22274091, 22007061)Youth Talent Support Program of Shanxi Province+1 种基金Program for the Top Young Academic Leaders of Higher Learning Institutions of ShanxiFundamental Research Program of Shanxi Province (No. 20210302123445)。
文摘In this work, we put forward a new and universal approach, i.e., cyanine ketone method, for fabricating meso–aryl heptamethine indocyanines, which is so simple that the treatment of the easy-to-get cyanine ketones with various aromatic lithium(Ar Li), followed by acidification, could straightforwardly give rise to the products in one-pot way. Importantly, due to the strong nucleophilicity of Ar Li, a series of bulky hydrophilic aromatic groups can be facilely integrated into the meso–position of heptamethine indocyanines, not only effectively inhibiting the undesired dye self-aggregation but also largely improving the water-solubility. Using one of anti-aggregation meso–aryl heptamethine indocyanines, we fabricated a dye-antibody conjugate for in vivo imaging tumor in a mouse model and achieved a high tumor-tonormal tissue ratio. The work laid a chemical foundation for constructing various meso–aryl heptamethine indocyanines, facilitating the advanced imaging and therapeutic applications in future.
文摘The review by Bangolo et al highlights the role of the gut microbiome in cancerassociated anemia(CAA).However,the impact of microbiome-derived metabolites is underexplored.In this letter,we focus on short-chain fatty acids,tryptophan metabolites,and polyamines as key mediators linking dysbiosis to impaired erythropoiesis and iron homeostasis.We also propose a research framework that integrates multi-omics analysis and gnotobiotic models.Finally,we discuss the clinical potential of metabolite-based diagnostics and microbiome-targeted therapies in managing CAA.
基金Financial support from National Key R&D Program of China(No.2023YFA1507203)National Natural Science Foundation of China(Nos.22371149,22188101)+2 种基金the Fundamental Research Funds for the Central Universities(No.63224098)Frontiers Science Center for New Organic Matter,Nankai University(No.63181206)the Haihe Laboratory of Sustainable Chemical Transformations for financial support。
文摘Herein,a metal-free electrochemical demethoxyl-cyanation of methoxyarenes via aromatic nucleophilic substitution(S_(N)Ar) using TMSCN as a cheap cyanide source under mild conditions has been presented.This transformation utilizes commercially available reagents,cheap electrodes,and simple equipment.Diverse aryl nitriles were successfully obtained in a direct and efficient way with broad substrate scope,excellent functional group tolerance,and selective C-O bond cleavage.Furthermore,late-stage modification of biorelevant compounds and gram-scale synthesis highlighted the potential application of the strategy.Mechanistic investigations suggest that the arene cation radical was considered as the key intermediate for the transformation,and undergoing the followed S_(N)Ar process.
基金project was supported by the National Key Research and Development Program(2021YFD2100700)。
文摘The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran sodium sulfate.Several Lactobacillus strains isolated from the healthy human fecal sample was found to utilize Trp to produce indole derivatives.The results of Trp metabolism indicated that the ability of Lactobacillus to metabolize Trp to produce indole-3-lactic acid(ILA),indole-3-carboxaldehyde(I3C),and indole-3-acetic acid varies in vitro and in vivo.The effect of Lactobacillus with high-yielding indole derivatives on disease activity index,colon length,and intestinal permeability was significantly better than that of Lactobacillus with low-yielding indole derivatives in a high Trp diet.And Lactobacillus combined with Trp intervention also had a certain regulatory effect on the intestinal flora of male BALB/c mice.Among them,Lactiplantibacillus plantarum DPUL-S164 produced more ILA both in vivo and in vitro,and the combination of L.plantarum DPUL-S164 and Trp significantly decreased the expression level of the serum pro-inflammatory cytokine interleukin(IL)-6 and increased the expression level of the anti-inflammatory cytokine IL-10,significantly improved the number of goblet cells in the mouse mucous layer and increased mucin and tight junction protein expression.Furthermore,L.plantarum DPUL-S164 combined with Trp intervention activated the aryl hydrocarbon receptors(Ah R)signaling pathway.Furthermore,we found that the expression of colonic tight junction protein was positively correlated with the expression of colonic Ah R,and the expression of Ah R was positively correlated with the concentrations of ILA and I3C in vivo.Therefore,we conclude that the ILA as Ah R ligand produced by L.plantarum DPUL-S164 regulated the Ah R pathway,thus up-regulating the expression of the tight junction protein and protecting the integrity of the epithelial barrier.
文摘The influence of the electronic and steric properties of bromoaromatic substrates on direct arylation polymerization for synthesizing high-molecular-weight conjugated polymers was investigated through a combination of experiments and calculations.Bromo-aromatic substrates with electron-withdrawing fluoro substituents exhibited higher yields and degrees of polymerization under PPh3-assisted conditions compared to those with electron-donating or bulky methyl substituents.Additionally,excessive steric hindrance at ortho-sites or overly electrondeficient dibromoaromatic substrates leads to reaction inactivation.Calculations indicated that electron-withdrawing substituents enhanced the electrophilicity of arylpalladium-PPh3intermediates,facilitating the activation of electron-rich arylative substrates and promoting polymer growth.Furthermore,steric hindrance from the substituents can influence the preferred reaction pathway,thereby increasing the real reaction barriers.Both experimental and computational results suggest that bromoaromatic substrates with optimized electron-deficient characteristics significantly improve monomer conversion and polymerization efficiency with n-hexylmethylether-substituted EDOT.These findings clarify how the electronic and steric properties of bromo-aromatic substrates affect EDOT derivative activation and are expected to aid in optimizing the polymerization conditions for the preparation of high-molecular-weight conjugated polymers.
基金the financial support from the Sichuan Science and Technology Program(No.2022NSFSC0619)。
文摘The asymmetric conjugate additions of aryl Grignard reagents to trisubstituted enones by chiral P,N ligand L6 with low catalyst loading(0.25–1.0 mol%)are disclosed.Chiral 2-ester chromanone and its analogs bearing a quaternary stereogenic centers at C2 position were produced in high to excellent yields,enantioselectivities and high turnover number.The notable features of this reaction include its broad substrate scope,complete 1,4-addition regioselectivities,applicability to both batch and flow for large scale synthesis.This report develops an efficient strategy to apply aryl Grignard reagents in asymmetric 1,4-conjugation reactions and provides a direct method to incorporate quaternary chiral centers toward the synthesis of biologically relevant chromanone derivatives.
文摘An efficient and novel approach is proposed for oxidative arylation of bio-based furfuryl alcohol(FA)to aryl furans(AFs),a versatile monomer of photoelectric materials,in the presence of UiO-67-Pd(F)with phenanthroline/bipyridine,and poly-F substituted phenyl ligands as the mixture linkers.The results of control experiments and theoretical calculations reveal that the–F on the phenyl linkers efficiently tunes the electron-deficient nature of Pd through the Zr_(6) clusters bridges,which favors the adsorption and activation of the furan ring.Furthermore,the conjugation of different nitrogen-containing ligands facilitates Pd coordination for the Heck-type insertion and subsequent electrophilic palladation,respectively.As a result,the oxidative arylation of FA derivatives is substantially enhanced because of these electronic and steric synergistic effects.Under the optimized conditions,72.2%FA conversion and 74.8%mono aryl furan(MAF)selectivity are shown in the Heck-type insertion.Meanwhile,85.3%of MAF is converted,affording 74.8%selectivity of final product(AFs)in the subsequent electrophilic palladation reaction.This process efficiency is remarkably higher than that with homogeneous catalysts.In addition,furan-benzene polymer obtained from the halogen-free synthesis catalyzed by UiO-67-Pd(F)show significantly better properties than that from conventional Suzuki coupling method.Therefore,the present work provides a new insight for useful AFs synthesis by oxidative arylation of bio-furan via rational tunning the metal center micro-environment of heterogeneous catalyst.
基金National Natural Science Foundation of China(Nos.22001177,22203023)Guangdong Pearl River Talent Program(no.2021QN020268)+3 种基金the Natural Science Foundation of Guangdong Province(Nos.2024A1515012381,2022A1515011859)Shenzhen Bay Laboratory Startup Fund(No.S201100003)Major Program of Shenzhen Bay Laboratory(No.S211101001-4)Shenzhen Bay Qihang Fellow Program(No.QH23001)for generous financial support.
文摘Chiral aryl cyclohex-3-en ether scaffold is widely present in bioactive natural products and drugs.The exploitation of efficient and enantioselective methods for the construction of aryl cyclohex-3-en ether scaffold is significant.Herein we disclose a chiral N,N’-dioxide/Lewis acid complex-catalyzed asymmetric inverse-electron-demand Diels-Alder(IEDDA)reaction using electron-deficient 3-carboalkoxyl-2-pyrones and less electron-enriched aryl enol ethers as reactants.A wide range of non-and 1,2-disubstituted acyclic aryl enol ethers are applicable to deliver diverse chiral bridged bicyclic lactones in high yields and stereoselectivities(up to 96%yield,>20:1 dr,97:3 er).The bridged bicyclic lactone core can be easily converted into chiral aryl cyclohex-3-en ether scaffold.Notably,DFT calculations revealed a stepwise and endo mechanism to explain the high enantioselectivity controlled by the cooperative effect of the steric factors and the dispersion interactions between ligands and enol ethers.
基金the National Key Research and Development Program of China(No.2021YFA1500100)the National Natural Science Foundation of China(Nos.92156017 and 21890722)+1 种基金“Frontiers Science Center for New Organic Matter”,Nankai University(No.63181206)Haihe Laboratory of Sustainable Chemical Transformation of Tianjin(No.24HHWCSS00019)for generous financial support。
文摘Mechanistic studies of the cleavage and transformation of unactivated C_(sp3)-H bonds are a significant field of chemistry.Overcoming the inherent low acidity of C-H bonds to activate the inert substrates is challenge under mild conditions.And their complex multi-step transformations may also hinder mechanistic understanding.Herein,we perform theoretical calculations and experimental studies to explore the C_(sp3)-H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA.A synergistic"main and auxiliary"model was revealed involving dual lithium metal by LDA dimers,and the aryl dilithium species as an intermediate base can facilitate C_(sp3)-H activation.This model not only aids in understanding the acidity of unactivated C_(sp3)-H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions,but also predicts unusual kinetic isotope effects(KIE)for newly designed 2-(methylthio)naphthalene that are experimentally validated.This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_(sp3)-H bonds and the development of new functionalities for alkali metal reagents.
基金supported by the National Natural Science Foundation of China(21373202,21525315)~~
文摘Covalent triazine-based frameworks（CTFs） are important microporous materials with a wide range of applications.Here,we demonstrate an environmentally benign and economic synthetic pathway to CTFs.The monomers used for CTFs,aromatic nitriles,were obtained by cyanation using nontoxic potassium hexacyanoferrate（Ⅱ） in place of commonly used toxic cyanides.Then,the CTFs were synthesized by trimerization of the corresponding cyano monomers in molten zinc chloride.A series of CTFs was synthesized,and the highest Brunauer-Emmett-Teller surface area measured in this series was 2404 m^2/g.Among the synthesized CTFs,CTF_（DCP） exhibited excellent CO_2 adsorption properties,with a CO_2 uptake of 225 mg/g at 0℃.
文摘In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.
基金supported by the Natural Science Foundation of Jiangsu Province of China(No.BK20140662)partially supported by the National Natural Science Foundation of China(No.81503319)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Although the etiology of inflammatory bowel disease is still tmcertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine （NOR）, an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1,8 production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）. Moreover, it significantly reduced expressions of cleaved IL-lfl, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide （LPS） and adenosine triphosphate （ATP）. Furthermore, NOR could activate aryl hydrocarbon receptor （AhR） in THP-1 cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90 complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter activity and binding activity of AhR/ARNT/XRE. Both siAhR and a-naphthoflavone （a-NF） markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.
基金supported by the Intercollegiate Key Scientific Research Projects of Henan Province(15A150018)~~
文摘An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed.This reaction was selective to N-arylation instead of C-arylation,which provides a simple synthetic method for N-aryl indoles.
基金by the National Science Council of the People’s Republic of China(No.2003AA33G030)
文摘A series of novel poly(aryl ether nitrile)s containing phthalazinone moiety were synthesized by the nucleophilic displacement reaction of bisphenol-like monomers(I)with 2,6-difluorobenzonitrile.The inherent viscosities ranged from 0.46 to 1.07 dL g^-1.The glass transition temperatures were in the range of 277-295℃,and the temperatures for 10%weight loss in nitrogen atmosphere were found between 495 and 527℃.The structures of these resultant polymers were confirmed by FT-IR and 1^H NMR.Moreover,the properties of poly(aryl ether nitrile)s including solubility and crystallinity were also studied.
