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Hydroxycarboxylic acid receptor 2 (HCAR2), modulated by endogenous ketone body ß-hydroxybutyrate and exogenous niacin, is a promising therapeutic target for inflammation-related diseases. HCAR2 mediates distinct pathophysiological events by activating Gi/o protein or ß-arrestin effectors. Here, we characterize compound 9n as a Gi-biased allosteric modulator (BAM) of HCAR2 and exhibit anti-inflammatory efficacy in RAW264.7 macrophages via a specific HCAR2-Gi pathway. Furthermore, four structures of HCAR2-Gi complex bound to orthosteric agonists (niacin or monomethyl fumarate), compound 9n, and niacin together with compound 9n simultaneously reveal a common orthosteric site and a unique allosteric site. Combined with functional studies, we decipher the action framework of biased allosteric modulation of compound 9n on the orthosteric site. Moreover, co-administration of compound 9n with orthosteric agonists could enhance anti-inflammatory effects in the mouse model of colitis. Together, our study provides insight to understand the molecular pharmacology of the BAM and facilitates exploring the therapeutic potential of the BAM with orthosteric drugs.
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Colite , Receptores Acoplados a Proteínas G , Animais , Camundongos , Regulação Alostérica , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP , Inflamação/tratamento farmacológico , Corpos Cetônicos , Niacina/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismoRESUMO
Trace-amine-associated receptors (TAARs), a group of biogenic amine receptors, have essential roles in neurological and metabolic homeostasis1. They recognize diverse endogenous trace amines and subsequently activate a range of G-protein-subtype signalling pathways2,3. Notably, TAAR1 has emerged as a promising therapeutic target for treating psychiatric disorders4,5. However, the molecular mechanisms underlying its ability to recognize different ligands remain largely unclear. Here we present nine cryo-electron microscopy structures, with eight showing human and mouse TAAR1 in a complex with an array of ligands, including the endogenous 3-iodothyronamine, two antipsychotic agents, the psychoactive drug amphetamine and two identified catecholamine agonists, and one showing 5-HT1AR in a complex with an antipsychotic agent. These structures reveal a rigid consensus binding motif in TAAR1 that binds to endogenous trace amine stimuli and two extended binding pockets that accommodate diverse chemotypes. Combined with mutational analysis, functional assays and molecular dynamic simulations, we elucidate the structural basis of drug polypharmacology and identify the species-specific differences between human and mouse TAAR1. Our study provides insights into the mechanism of ligand recognition and G-protein selectivity by TAAR1, which may help in the discovery of ligands or therapeutic strategies for neurological and metabolic disorders.
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Proteínas de Ligação ao GTP , Receptores Acoplados a Proteínas G , Animais , Humanos , Camundongos , Aminas/metabolismo , Anfetamina/metabolismo , Antipsicóticos/química , Antipsicóticos/metabolismo , Sítios de Ligação , Catecolaminas/agonistas , Catecolaminas/química , Catecolaminas/metabolismo , Microscopia Crioeletrônica , Proteínas de Ligação ao GTP/química , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/ultraestrutura , Ligantes , Simulação de Dinâmica Molecular , Mutação , Polifarmacologia , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/ultraestrutura , Especificidade da Espécie , Especificidade por SubstratoRESUMO
Cannabis sativa is known for its therapeutic benefit in various diseases including pain relief by targeting cannabinoid receptors. The primary component of cannabis, Δ9-tetrahydrocannabinol (THC), and other agonists engage the orthosteric site of CB1, activating both Gi and ß-arrestin signaling pathways. The activation of diverse pathways could result in on-target side effects and cannabis addiction, which may hinder therapeutic potential. A significant challenge in pharmacology is the design of a ligand that can modulate specific signaling of CB1. By leveraging insights from the structure-function selectivity relationship (SFSR), we have identified Gi signaling-biased agonist-allosteric modulators (ago-BAMs). Further, two cryoelectron microscopy (cryo-EM) structures reveal the binding mode of ago-BAM at the extrahelical allosteric site of CB1. Combining mutagenesis and pharmacological studies, we elucidated the detailed mechanism of ago-BAM-mediated biased signaling. Notably, ago-BAM CB-05 demonstrated analgesic efficacy with fewer side effects, minimal drug toxicity and no cannabis addiction in mouse pain models. In summary, our finding not only suggests that ago-BAMs of CB1 provide a potential nonopioid strategy for pain management but also sheds light on BAM identification for GPCRs.
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Microscopia Crioeletrônica , Receptor CB1 de Canabinoide , Transdução de Sinais , Receptor CB1 de Canabinoide/metabolismo , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/química , Animais , Regulação Alostérica/efeitos dos fármacos , Camundongos , Humanos , Transdução de Sinais/efeitos dos fármacos , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/genética , Células HEK293 , Relação Estrutura-Atividade , Dronabinol/farmacologia , Dronabinol/química , Dronabinol/análogos & derivados , Cannabis/química , Cannabis/metabolismoRESUMO
Cross-linkers play a critical role in capturing protein dynamics in chemical cross-linking mass spectrometry techniques. Various types of cross-linkers with different backbone features are widely used in the study of proteins. However, it is still not clear how the cross-linkers' backbone affect their own structure and their interactions with proteins. In this study, we systematically characterized and compared methylene backbone and polyethylene glycol (PEG) backbone cross-linkers in terms of capturing protein structure and dynamics. The results indicate the cross-linker with PEG backbone have a better ability to capture the inter-domain dynamics of calmodulin, adenylate kinase, maltodextrin binding protein and dual-specificity protein phosphatase. We further conducted quantum chemical calculations and all-atom molecular dynamics simulations to analyze thermodynamic and kinetic properties of PEG backbone and methylene backbone cross-linkers. Solution nuclear magnetic resonance was employed to validate the interaction interface between proteins and cross-linkers. Our findings suggest that the polarity distribution of PEG backbone enhances the accessibility of the cross-linker to the protein surface, facilitating the capture of sites located in dynamic regions. By comprehensively benchmarking with disuccinimidyl suberate (DSS)/bis-sulfosuccinimidyl-suberate(BS3), bis-succinimidyl-(PEG)2 revealed superior advantages in protein dynamic conformation analysis in vitro and in vivo, enabling the capture of a greater number of cross-linking sites and better modeling of protein dynamics. Furthermore, our study provides valuable guidance for the development and application of PEG backbone cross-linkers.
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Polietilenoglicóis , Proteínas , Polietilenoglicóis/química , Proteínas/química , Espectrometria de Massas , Conformação Proteica , Simulação de Dinâmica MolecularRESUMO
GPR34 is a functional G-protein-coupled receptor of Lysophosphatidylserine (LysoPS), and has pathogenic roles in numerous diseases, yet remains poorly targeted. We herein report a cryo-electron microscopy (cryo-EM) structure of GPR34 bound with LysoPS (18:1) and Gi protein, revealing a unique ligand recognition mode with the negatively charged head group of LysoPS occupying a polar cavity formed by TM3, 6 and 7, and the hydrophobic tail of LysoPS residing in a lateral open hydrophobic groove formed by TM3-5. Virtual screening and subsequent structural optimization led to the identification of a highly potent and selective antagonist (YL-365). Design of fusion proteins allowed successful determination of the challenging cryo-EM structure of the inactive GPR34 complexed with YL-365, which revealed the competitive binding of YL-365 in a portion of the orthosteric binding pocket of GPR34 and the antagonist-binding-induced allostery in the receptor, implicating the inhibition mechanism of YL-365. Moreover, YL-365 displayed excellent activity in a neuropathic pain model without obvious toxicity. Collectively, this study offers mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, and provides proof of concept that targeting GPR34 represents a promising strategy for disease treatment.
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Inibição Psicológica , Neuralgia , Humanos , Microscopia Crioeletrônica , Ligação CompetitivaRESUMO
Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.
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Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.
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Chalcogen bond (ChB) catalysis, as a new type in the field of non-covalent bond catalysis, has become a hot research topic in the field of organocatalysis in recent years. In the present work, we investigated the catalytic performance of a series of hypervalent ChB catalysis based on the intramolecular Aza-Michael reaction of aminochalcone. The reaction includes the carbon-nitrogen bond coupling step (key step) and the proton transfer step. The catalytic performance of mono-dentate pentafluorophenyl chalcogen bond donor ChB1 was comparable to that of bis-dentate chalcogen bond donor ChB4, and stronger than that of mono-dentate chalcogen bond donors ChB2 and ChB3. The formation of the chalcogen bond between the catalyst and the carbonyl oxygen atom of the reactant, causing the charge rearrangement of the reactant and C(1) charge of the -C-Ph group to become more positive, thereby the ChB catalysis promoted the nucleophile reaction. The electron density of the chalcogen bond of the pre-complex, the most positive electrostatic potentials of the catalyst, and the NPA charge of the key atom are proportional to the Gibbs energy barrier of the C-N bond coupling process, which provides an idea to predict the catalytic activity of the ChB catalysis.
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Chalcogen bond catalysis, particularly cationic hypervalent chalcogen bond catalysis, is considered to be an effective strategy for organocatalysis. In this work, the cationic hypervalent chalcogen bond catalysis for the Povarov reaction between N-benzylideneaniline and ethyl vinyl ether was investigated by density functional theory (DFT). The catalytic reaction involves the cycloaddition process and the proton transfer process, and the rate-determining step is the cycloaddition process. Cationic hypervalent tellurium derivatives bearing CF3 and F groups exhibit superior catalytic activity. For the rate-determining step, the Gibbs free energy barrier decreases as the positive electrostatic potential of the chalcogen bond catalysts increases. More importantly, the Gibbs free energy barrier has a strong linear correlation with the electrostatic energy of the chalcogen bond in the catalyst-substrate complex. Furthermore, the catalytic reactions include the endo pathway and exo pathway. The C-Hâ â â π interaction between the substituent of the ethyl vinyl ether and the aryl ring of the N-benzylideneaniline contributes to the endo-selectivity of the reaction. This research contributes to a deeper understanding of chalcogen bond catalysis, providing insights for designing chalcogen bond catalysts with high performance.
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Lanthipeptides are an important group of natural products with diverse biological functions, and their biosynthesis requires the removal of N-terminal leader peptides (LPs) by designated proteases. LanPM1 enzymes, a subgroup of M1 zinc-metallopeptidases, have been recently identified as bifunctional proteases with both endo- and aminopeptidase activities to remove LPs of class III and class IV lanthipeptides. Herein, we report the biochemical and structural characterization of EryP as the LanPM1 enzyme from the biosynthesis of class III lanthipeptide erythreapeptin. We determined X-ray crystal structures of EryP in three conformational states, the open, intermediate and closed states, and identified a unique interdomain Ca2+ binding site as a regulatory element that modulates its domain dynamics and proteolytic activity. Inspired by this regulatory Ca2+ binding, we developed a strategy to engineer LanPM1 enzymes for enhanced catalytic activities by strengthening interdomain associations and driving the conformational equilibrium toward their closed forms.
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Lipopolissacarídeos , Zinco , Metaloproteases/metabolismo , Peptídeo Hidrolases/metabolismo , Peptídeos/metabolismo , Sinais Direcionadores de ProteínasRESUMO
Hypertrophic ligamentum flavum (LF) is a main factor responsible for lumbar spinal stenosis (LSS); however, the exact mechanisms of the pathogenesis of these processes remain unknown. This study aimed to elucidate whether circular RNAs and microRNAs regulate the pathogenesis of LF and LSS, especially focusing on circPDK1 (hsa_circ_0057105), a circRNA targeting pyruvate dehydrogenase kinase 1 and differentially expressed in LF tissues between lumbar disk herniation and LSS patients. The circPDK1/miR-4731 and miR-4731/TNXB (Tenascin XB) interactions were predicted and validated by luciferase reporter assay. Colony formation, wound-healing, and MTT assays were used for estimating cell proliferation and migration. Protein expression levels were evaluated using Western blotting. TNXB expression was verified using immunohistochemistry (IHC). Overexpressing circPDK1 promoted the proliferation, migration, and expression of fibrosis-related protein (alpha smooth muscle actin (α-SMA), lysyl oxidase like 2 (LOXL2), Collagen I, matrix metalloproteinase-2 (MMP-2) and TNXB) in LF whereas miR-4731-5p showed opposite effects. The expression of TNXB was promoted by circPDK1; contrary results were observed with miR-4731-5p. Co-overexpression of miR-4731-5p partially reversed the proliferative and fibrosis-prompting effects of circPDK1 or TNXB. The circPDK1-miR-4731-TNXB pathway may be proposed as a regulatory axis in LF hypertrophy, which might shed light on in-depth research of LSS, as well as providing a novel therapeutic target for LF hypertrophy-induced LSS.
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Ligamento Amarelo , MicroRNAs , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Ligamento Amarelo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose , Hipertrofia/metabolismoRESUMO
BACKGROUND: Inflammatory macrophage infiltration plays a critical role in acute kidney disease induced by ischemia-reperfusion (IRI-AKI). Calycosin is a natural flavone with multiple bioactivities. This study aimed to investigate the therapeutic role of calycosin in IRI-AKI and its underlying mechanism. METHODS: The renoprotective and anti-inflammatory effects of calycosin were analyzed in C57BL/6 mice with IRI-AKI and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA-seq was used for mechanism investigation. The molecular target of calycosin was screened by in silico methods and validated by surface plasmon resonance (SPR). Macrophage chemotaxis was analyzed using Transwell and agarose gel spot assays. RESULTS: Calycosin treatment significantly reduced serum creatinine and urea nitrogen and attenuated tubular destruction in IRI-AKI mice. Additionally, calycosin markedly suppressed NF-κB signaling activation and the expression of inflammatory mediators IL-1ß and TNF-α in IRI-AKI kidneys and LPS-stimulated RAW 264.7 cells. Interestingly, RNA-seq revealed calycosin remarkably downregulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was downregulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in silico target prediction, molecular docking, and SPR assay demonstrated that calycosin directly binds to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells. CONCLUSIONS: In summary, calycosin attenuates IRI-AKI by inhibiting MIF-mediated macrophage inflammatory chemotaxis, suggesting it could be a promising therapeutic agent for the treatment of IRI-AKI.
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Injúria Renal Aguda , Quimiotaxia , Isoflavonas , Fatores Inibidores da Migração de Macrófagos , Macrófagos , Traumatismo por Reperfusão , Animais , Masculino , Camundongos , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Quimiotaxia/efeitos dos fármacos , Oxirredutases Intramoleculares/metabolismo , Oxirredutases Intramoleculares/genética , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Células RAW 264.7 , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
As important noncovalent interactions, halogen bonds have been widely used in material science, supramolecular chemistry, medicinal chemistry, organocatalysis, and other fields. In the past 15 years, halogen bond catalysis has become a developed field in organocatalysis for the catalysts' advantages of being environmentally friendly, inexpensive, and recyclable. Halogen bonds can induce various organic reactions, and halogen bond catalysis has become a powerful alternative to the fully explored hydrogen bond catalysis. From a physical chemistry view, this perspective provides an overview of the latest progress and key examples of halogen bond catalysis via activation of the lone pair systems of organic functional group, π systems, and metal complexes. The research progresses in halogen bond catalysis by our group were also introduced.
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Aflatoxin B1 (AFB1) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious antioxidant capable of shielding the liver from oxidative harm. This study aimed to examine the damage caused by AFB1 on bovine hepatic cells and the protective role of allicin against AFB1-induced cytotoxicity. In this study, cells were pretreated with allicin before the addition of AFB1 for co-cultivation. Our findings indicate that AFB1 compromises cellular integrity, suppresses the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, allicin attenuates oxidative damage to bovine hepatic cells caused by AFB1 by promoting the expression of the Nrf2 pathway and reducing cell apoptosis. In conclusion, the results of this study will help advance clinical research and applications, providing new options and directions for the prevention and treatment of liver diseases.
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Aflatoxina B1 , Antioxidantes , Apoptose , Dissulfetos , Hepatócitos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Transdução de Sinais , Ácidos Sulfínicos , Animais , Ácidos Sulfínicos/farmacologia , Aflatoxina B1/toxicidade , Bovinos , Dissulfetos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antioxidantes/farmacologia , FemininoRESUMO
The booming development of rare earth industry and the extensive utilization of its products accompanied by urban development have led to the accelerated accumulation of rare earth elements (REEs) as emerging pollutants in atmospheric environment. In this study, the variation of REEs in PM2.5 with urban (a non-mining city) transformation was investigated through five consecutive years of sample collection. The compositional variability and provenance contribution of REEs in PM2.5 were characterized, and the REEs exposure risks of children and adults via inhalation, ingestion and dermal absorption were also evaluated. The results showed an increase in the total REEs concentration from 46.46 ± 35.16 mg/kg (2017) to 81.22 ± 38.98 mg/kg (2021) over the five-year period, with Ce and La making the largest contribution. The actual increment of industrial and traffic emission source among the three pollution sources was 1.34 ng/m3. Coal combustion source displayed a downward trend. Ingestion was the main exposure pathway for REEs in PM2.5 for both children and adults. Ce contributed the most to the total intake of REEs in PM2.5 among the population, followed by La and Nd. The exposure risks of REEs in PM2.5 in the region were relatively low, but the trend of change was of great concern. It was strongly recommended to strengthen the concern about traffic-related non-exhaust emissions of particulate matter.
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Poluentes Atmosféricos , Metais Terras Raras , Adulto , Criança , Humanos , Poluentes Atmosféricos/análise , Material Particulado/análise , Cidades , Monitoramento Ambiental/métodos , Metais Terras Raras/análise , ChinaRESUMO
OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.
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Displasia Broncopulmonar , Recém-Nascido Prematuro , Gêmeos , Humanos , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/epidemiologia , Fatores de Risco , Recém-Nascido , Feminino , Estudos Retrospectivos , Masculino , Idade Gestacional , Peso ao Nascer , Modelos LogísticosRESUMO
Single-atom catalysts exhibit promising electrocatalytic activity, a trait that can be further enhanced through the introduction of heteroatom doping within the carbon skeleton. Nonetheless, the intricate relationship between the doping positions and activity remains incompletely elucidated. This contribution sheds light on an inductive effect of single-atom sites, showcasing that the activity of the oxygen reduction reaction (ORR) can be augmented by reducing the spatial gap between the doped heteroatom and the single-atom sites. Drawing inspiration from this inductive effect, we propose a synthesis strategy involving ligand modification aimed at precisely adjusting the distance between dopants and single-atom sites. This precise synthesis leads to optimized electrocatalytic activity for the ORR. The resultant electrocatalyst, characterized by Fe-N3P1 single-atom sites, demonstrates remarkable ORR activity, thus exhibiting great potential in zinc-air batteries and fuel cells.
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Recently, the green and high efficient of chalcogen bond (ChB) catalysis has been aroused great interest. In this work, the ChB catalysis has been applied to the intramolecular Rauhut-Currier (RC) reaction of bis(enones). The mechanism was divided into four processes: the promoter addition process, the carbon-carbon bond coupling process, the hydrogen transfer process, and the promoter elimination process. This study shows that the ChB catalyst could act on the promoter and reactant in the RC reaction, respectively. And the path 2 of ChB catalyst direct acting on the reactant is considered to be a relatively favorable channel of the reaction due to a lower energy barrier. In addition, all six catalysts could achieve good catalytic effect. Analysis of the properties shows that the formation of chalcogen bond mainly promotes the charge transfer of LP(O)-BD*(C-Se) in the carbon-carbon bond formation (key step), so that the charge of C(4) atom become more positive, thereby accelerating the reaction.
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Recently, chalcogen bond catalysts with telluronium cations have garnered considerable attention in organic reactions. In this work, chalcogen bond catalysis on the bromination reaction of anisole with N-bromosuccinimide (NBS) with the telluronium cationic catalysts has been explored with density functional theory (DFT). The catalytic reaction is divided into two stages: the bromine transfer step and the proton transfer step. Based on the computational results, one can find the rate-determining step is the bromine transfer step. Moreover, the present study elucidates that a stronger chalcogen bond between catalysts and NBS will give better catalytic performance. Additionally, this work also clarified the importance of the electrostatic and polarization effects in the chalcogen bond between the oxygen atom of NBS and the Te atom of the catalyst in this bromination reaction. The electrostatic and polarization effects are significantly influenced by the electron-withdrawing ability of the substitution groups on the catalysts. Moreover, the structure-property relationship between the strength of chalcogen bond, electrostatic effect, polarization effect and catalytic performance are established for the design of more efficient chalcogen bond catalysts.
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An efficient triflic anhydride promoted phosphorylation of ketone was disclosed, and vinylphosphorus compounds were prepared under solvent- and metal-free conditions. Both aryl and alkyl ketones could perform smoothly to give vinyl phosphonates in high to excellent yields. In addition, the reaction was easy to carry out and easy to scale up. Mechanistic studies suggested that this transformation might involve nucleophilic vinylic substitution or a nucleophilic addition-elimination mechanism.