ACS Central Science最新文献_第3页

Unexpected Damage on Metal Artifacts Triggered by the Hazardous Interfacial Interaction from Aging of Polymer Coatings. 聚合物涂层老化引起的有害界面相互作用对金属工件的意外损伤。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-23 eCollection Date: 2025-05-28 DOI: 10.1021/acscentsci.5c00067

Ying An, Pei Hu, Kaitao Li, Yu Kang, Gang Hu, Rui Tian, Chao Lu, Xue Duan

{"title":"Unexpected Damage on Metal Artifacts Triggered by the Hazardous Interfacial Interaction from Aging of Polymer Coatings.","authors":"Ying An, Pei Hu, Kaitao Li, Yu Kang, Gang Hu, Rui Tian, Chao Lu, Xue Duan","doi":"10.1021/acscentsci.5c00067","DOIUrl":"10.1021/acscentsci.5c00067","url":null,"abstract":"Polymer coatings are currently being employed for preservation of metal artifacts. However, there is insufficient awareness that inevitable aging of polymer coatings is bound to damage metal artifacts due to the lack of a direct and sensitive methodology to study the aging behaviors of polymers coated on the artifacts. Herein, we have developed an in situ and three-dimensional strategy to visualize the early stage aging behaviors of polymers coated on metal artifacts by lighting carboxyl groups generated from polymer aging. It is disclosed that polymer aging occurred simultaneously at the surface and the interface with metal artifacts, generating carboxyl groups and hydroxyl radicals to induce the corrosion and oxidation of metallic artifacts. In turn, the generated metallic ions could further aggravate the aging of polymer coatings, manifested as the larger volume of the aged sites at the interface with metal artifacts in comparison with that at the surface of polymer coatings. Such a circular reaction is validated using real metal artifact samples. These findings raised a timely alarm for the conservation ability and potential threat of polymer coatings on metal artifacts. It is anticipated that the proposed strategy could provide solid supports for the implementation of advanced conservation strategies for metal artifacts.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"694-703"},"PeriodicalIF":12.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Click Coupling Chemistry to Explore Glycan Recognition 新的键偶联化学探索聚糖识别

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-23 DOI: 10.1021/acscentsci.4c0212410.1021/acscentsci.4c02124

Tianwei Jia, Akul Y. Mehta, Catherine A. Tilton, Ea Kristine Clarisse Tulin, Lauren E. Pepi, Lukas Muerner, Stephan von Gunten, Jamie Heimburg-Molinaro, Sean R. Stowell and Richard D. Cummings*,

{"title":"Novel Click Coupling Chemistry to Explore Glycan Recognition","authors":"Tianwei Jia, Akul Y. Mehta, Catherine A. Tilton, Ea Kristine Clarisse Tulin, Lauren E. Pepi, Lukas Muerner, Stephan von Gunten, Jamie Heimburg-Molinaro, Sean R. Stowell and Richard D. Cummings*, ","doi":"10.1021/acscentsci.4c0212410.1021/acscentsci.4c02124","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02124https://doi.org/10.1021/acscentsci.4c02124","url":null,"abstract":"Specific recognition of glycans by proteins is important in many biological processes and immune responses. Here we present a general approach for derivatizing free glycans with a novel linker MTZ (3-(methoxyamino)propylamine added to a bioorthogonal-functional tetrazine tag) that exploits click chemistry to generate multiple platforms of glycan coupling. This derivatization preserves glycan integrity, is reversible and quantifiable, and incorporates a bioorthogonal tetrazine tag for click coupling. A library of ABO(H) blood group MTZ-glycans was efficiently conjugated to avidin Luminex beads through a Biotin-PEG11-TCO (trans-cyclooctene) spacer, generating a multiplex array that was reproducibly interrogated in a high-throughput Luminex approach with multiple lectins and antibodies. We also rapidly profiled antiglycan IgG, IgM, and IgA antibodies in multiple, serially diluted human serum samples, revealing unique repertoires of antiglycan responses in each sera. Glycans were efficiently coupled to bovine serum albumin (BSA) at a high density (∼19–24 glycans/BSA) to generate a neoglycoprotein library that was useful in microarray formats that provided results equivalent to those obtained from the Luminex approach. Neoglycoproteins have many uses, including serving as acceptors for glycosyltransferases, as we demonstrate for assays of ST6Gal1 sialyltransferase. These facile and efficient technologies significantly expand the toolbox available to explore glycan–GBP interactions.A general method that spans the initial design of a multifunctional linker to its broad application across multiple analysis techniques to explore protein−glycan interactions.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"753–769 753–769"},"PeriodicalIF":12.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unexpected Damage on Metal Artifacts Triggered by the Hazardous Interfacial Interaction from Aging of Polymer Coatings 聚合物涂层老化引起的有害界面相互作用对金属工件的意外损伤

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-23 DOI: 10.1021/acscentsci.5c0006710.1021/acscentsci.5c00067

Ying An, Pei Hu, Kaitao Li, Yu Kang, Gang Hu, Rui Tian*, Chao Lu* and Xue Duan,

{"title":"Unexpected Damage on Metal Artifacts Triggered by the Hazardous Interfacial Interaction from Aging of Polymer Coatings","authors":"Ying An, Pei Hu, Kaitao Li, Yu Kang, Gang Hu, Rui Tian*, Chao Lu* and Xue Duan, ","doi":"10.1021/acscentsci.5c0006710.1021/acscentsci.5c00067","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00067https://doi.org/10.1021/acscentsci.5c00067","url":null,"abstract":"Polymer coatings are currently being employed for preservation of metal artifacts. However, there is insufficient awareness that inevitable aging of polymer coatings is bound to damage metal artifacts due to the lack of a direct and sensitive methodology to study the aging behaviors of polymers coated on the artifacts. Herein, we have developed an in situ and three-dimensional strategy to visualize the early stage aging behaviors of polymers coated on metal artifacts by lighting carboxyl groups generated from polymer aging. It is disclosed that polymer aging occurred simultaneously at the surface and the interface with metal artifacts, generating carboxyl groups and hydroxyl radicals to induce the corrosion and oxidation of metallic artifacts. In turn, the generated metallic ions could further aggravate the aging of polymer coatings, manifested as the larger volume of the aged sites at the interface with metal artifacts in comparison with that at the surface of polymer coatings. Such a circular reaction is validated using real metal artifact samples. These findings raised a timely alarm for the conservation ability and potential threat of polymer coatings on metal artifacts. It is anticipated that the proposed strategy could provide solid supports for the implementation of advanced conservation strategies for metal artifacts.Hazardous interfacial interaction was visualized between polymer coatings and metallic artifacts, resulting in the simultaneously aggravated polymer aging and corroded metallic artifacts.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"694–703 694–703"},"PeriodicalIF":12.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Framework Membranes for Aqueous Batteries: From Microporous, Mesoporous to Macroporous Structures 水电池框架膜：从微孔、介孔到大孔结构

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-17 DOI: 10.1021/acscentsci.5c0036510.1021/acscentsci.5c00365

Lin Liu, Jiahao Chen, Ahmed Elzatahry, Dongliang Chao* and Dongyuan Zhao*,

{"title":"Framework Membranes for Aqueous Batteries: From Microporous, Mesoporous to Macroporous Structures","authors":"Lin Liu, Jiahao Chen, Ahmed Elzatahry, Dongliang Chao* and Dongyuan Zhao*, ","doi":"10.1021/acscentsci.5c0036510.1021/acscentsci.5c00365","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00365https://doi.org/10.1021/acscentsci.5c00365","url":null,"abstract":"To pursue high safety and more affordable energy storage systems, aqueous batteries (ABs) have become a promising contender. Nevertheless, critical challenges persist in diverse AB systems for large-scale applications, including dendrite growth, ion shuttle effects, hydrogen evolution, and corrosion. Notably, owing to the high specific surface area, tunable pore size, and easy multifunctionalization, framework membranes have garnered significant attention as key components for enhancing the performance of ABs. In this context, it is necessary to summarize and discuss the precise pore architecture design of framework membranes in regulating the ionic conductivity and selectivity, to gain an in-depth and comprehensive understanding. The categorization from microporous, mesoporous, to macroporous framework membranes aims to rationally evaluate the structure-performance relationships. Finally, perspectives on the potential applications of framework membranes in ABs are discussed, offering valuable insights for future research and development.Precise pore architecture design─tailoring micro-, meso-, and macroporous structures in framework membranes─addresses ionic conductivity and selectivity challenges in aqueous batteries.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"659–664 659–664"},"PeriodicalIF":12.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Framework Membranes for Aqueous Batteries: From Microporous, Mesoporous to Macroporous Structures. 水电池框架膜：从微孔、介孔到大孔结构。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-17 eCollection Date: 2025-05-28 DOI: 10.1021/acscentsci.5c00365

Lin Liu, Jiahao Chen, Ahmed Elzatahry, Dongliang Chao, Dongyuan Zhao

{"title":"Framework Membranes for Aqueous Batteries: From Microporous, Mesoporous to Macroporous Structures.","authors":"Lin Liu, Jiahao Chen, Ahmed Elzatahry, Dongliang Chao, Dongyuan Zhao","doi":"10.1021/acscentsci.5c00365","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00365","url":null,"abstract":"To pursue high safety and more affordable energy storage systems, aqueous batteries (ABs) have become a promising contender. Nevertheless, critical challenges persist in diverse AB systems for large-scale applications, including dendrite growth, ion shuttle effects, hydrogen evolution, and corrosion. Notably, owing to the high specific surface area, tunable pore size, and easy multifunctionalization, framework membranes have garnered significant attention as key components for enhancing the performance of ABs. In this context, it is necessary to summarize and discuss the precise pore architecture design of framework membranes in regulating the ionic conductivity and selectivity, to gain an in-depth and comprehensive understanding. The categorization from microporous, mesoporous, to macroporous framework membranes aims to rationally evaluate the structure-performance relationships. Finally, perspectives on the potential applications of framework membranes in ABs are discussed, offering valuable insights for future research and development.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"659-664"},"PeriodicalIF":12.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12132988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plug Flow: Generating Renewable Electricity with Water from Nature by Breaking the Limit of Debye Length 塞流：突破德拜长度极限，利用自然之水产生可再生电力

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-16 DOI: 10.1021/acscentsci.4c0211010.1021/acscentsci.4c02110

Chi Kit Ao, Yajuan Sun, Yan Jie Neriah Tan, Yan Jiang, Zhenxing Zhang, Chengyu Zhang and Siowling Soh*,

{"title":"Plug Flow: Generating Renewable Electricity with Water from Nature by Breaking the Limit of Debye Length","authors":"Chi Kit Ao, Yajuan Sun, Yan Jie Neriah Tan, Yan Jiang, Zhenxing Zhang, Chengyu Zhang and Siowling Soh*, ","doi":"10.1021/acscentsci.4c0211010.1021/acscentsci.4c02110","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02110https://doi.org/10.1021/acscentsci.4c02110","url":null,"abstract":"Charge separation occurs spontaneously at the solid–liquid interface, forming an electric double layer. Previous methods, including streaming current, used to harvest the constantly separated charge in micron-sized and larger systems reported negligible power output due to the fundamental limit caused by the very short nanoscale Debye length. This study reports on the phenomenon that plug flow of water that falls naturally down a millimeter-sized tube generates electricity with a high efficiency of >10% and power density of ∼100 W/m2. This high power breaks the theoretical limit defined by the Debye length in macroscale channels. Plug flow generates 5 orders of magnitude more electricity than continuous flow (i.e., streaming current) and more than other technologies using falling water. Plug flow triggers a unique interfacial chemistry with large chemical potential of charge separation: the complete spatial separation of aqueous H+ and OH– ions without the electric double layer. Having macroscale channels enables the energy of water from nature (e.g., rain or rivers) to be harvested freely. The simple setup lights up multiple LEDs continuously, modifies surfaces, and performs chemical reactions. Plug flow via harvesting energy from nature is a source of renewable power with many advantages for achieving sustainable societies.Plug flow has a huge chemical potential of charge separation at the solid−liquid interface not limited by the Debye length for effectively generating electricity via harvesting energy from rain.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"719–733 719–733"},"PeriodicalIF":12.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling Small Molecule-Mediated Sirtuin 3 Activation at a Distinct Binding Site for Cardioprotective Therapies. 揭示小分子介导的Sirtuin 3激活在一个独特的结合位点上用于心脏保护治疗。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-14 eCollection Date: 2025-05-28 DOI: 10.1021/acscentsci.5c00023

Dan Zhang, Jifa Zhang, Chengyong Wu, Yao Xiao, Liwei Ji, Jiarui Hu, Jianjun Ding, Tao Li, Yiwen Zhang, Liang Ouyang

{"title":"Unraveling Small Molecule-Mediated Sirtuin 3 Activation at a Distinct Binding Site for Cardioprotective Therapies.","authors":"Dan Zhang, Jifa Zhang, Chengyong Wu, Yao Xiao, Liwei Ji, Jiarui Hu, Jianjun Ding, Tao Li, Yiwen Zhang, Liang Ouyang","doi":"10.1021/acscentsci.5c00023","DOIUrl":"10.1021/acscentsci.5c00023","url":null,"abstract":"Sirtuin 3 (SIRT3), a pivotal mitochondrial deacetylase, plays a critical role in restoring mitochondrial function, particularly through the activation of autophagy. Despite its promise as a cardioprotective target, developing SIRT3 activators and their therapeutic applications remains challenging. Here, we report the identification of SKLB-11A, a SIRT3 activator with submicromolar affinity and high efficacy. Structural and mutagenesis analyses revealed a unique allosteric site for SKLB-11A in SIRT3, where a conformational change in Leu298 drives its potent activation. Subsequent studies demonstrated that SKLB-11A drives autophagy/mitophagy signaling pathways, effectively preventing mitochondrial dysfunction, and improving cardiac dysfunction in both doxorubicin (Dox)-induced cardiotoxicity and myocardial ischemia/reperfusion (I/R) models. Collectively, our data highlight the potential of pharmacological SIRT3 activation as an effective therapeutic strategy for cardioprotection. SKLB-11A, as a first-in-class SIRT3 allosteric activator with a distinct binding mode, not only offers a valuable tool for exploring the physiological and pathological roles of SIRT3 deacetylation but also holds promise for the development of targeted cardioprotective therapies.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"704-718"},"PeriodicalIF":12.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling Small Molecule-Mediated Sirtuin 3 Activation at a Distinct Binding Site for Cardioprotective Therapies 揭示小分子介导的Sirtuin 3激活在一个独特的结合位点上用于心脏保护治疗

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-13 DOI: 10.1021/acscentsci.5c0002310.1021/acscentsci.5c00023

Dan Zhang, Jifa Zhang, Chengyong Wu, Yao Xiao, Liwei Ji, Jiarui Hu, Jianjun Ding, Tao Li*, Yiwen Zhang* and Liang Ouyang*,

{"title":"Unraveling Small Molecule-Mediated Sirtuin 3 Activation at a Distinct Binding Site for Cardioprotective Therapies","authors":"Dan Zhang, Jifa Zhang, Chengyong Wu, Yao Xiao, Liwei Ji, Jiarui Hu, Jianjun Ding, Tao Li*, Yiwen Zhang* and Liang Ouyang*, ","doi":"10.1021/acscentsci.5c0002310.1021/acscentsci.5c00023","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00023https://doi.org/10.1021/acscentsci.5c00023","url":null,"abstract":"Sirtuin 3 (SIRT3), a pivotal mitochondrial deacetylase, plays a critical role in restoring mitochondrial function, particularly through the activation of autophagy. Despite its promise as a cardioprotective target, developing SIRT3 activators and their therapeutic applications remains challenging. Here, we report the identification of SKLB-11A, a SIRT3 activator with submicromolar affinity and high efficacy. Structural and mutagenesis analyses revealed a unique allosteric site for SKLB-11A in SIRT3, where a conformational change in Leu298 drives its potent activation. Subsequent studies demonstrated that SKLB-11A drives autophagy/mitophagy signaling pathways, effectively preventing mitochondrial dysfunction, and improving cardiac dysfunction in both doxorubicin (Dox)-induced cardiotoxicity and myocardial ischemia/reperfusion (I/R) models. Collectively, our data highlight the potential of pharmacological SIRT3 activation as an effective therapeutic strategy for cardioprotection. SKLB-11A, as a first-in-class SIRT3 allosteric activator with a distinct binding mode, not only offers a valuable tool for exploring the physiological and pathological roles of SIRT3 deacetylation but also holds promise for the development of targeted cardioprotective therapies.SKLB-11A is identified as a novel allosteric SIRT3 activator with significant cardioprotective effects, elucidating a unique activation mechanism via cocrystal structure and functional assays.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 5","pages":"704–718 704–718"},"PeriodicalIF":12.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Multicomponent Reaction-Based Platform Opens New Avenues in Aryl Hydrocarbon Receptor Modulation. 基于多组分反应的平台为芳基烃受体调节开辟了新途径。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-10 eCollection Date: 2025-04-23 DOI: 10.1021/acscentsci.5c00194

Pau Nadal Rodríguez, Frederick Hartung, Marina Pedrola, Seemon Coomar, Alejandro Diaz-Moreno, Anna M Hätälä, Katharina M Rolfes, Ismael Sánchez-Vera, Joan Gil, Elies Molins, Antonio Viayna, Alexander Hanzl, Nicolas H Thomä, Thomas Haarmann-Stemmann, F Javier Luque, Rodolfo Lavilla, Ouldouz Ghashghaei

{"title":"A Multicomponent Reaction-Based Platform Opens New Avenues in Aryl Hydrocarbon Receptor Modulation.","authors":"Pau Nadal Rodríguez, Frederick Hartung, Marina Pedrola, Seemon Coomar, Alejandro Diaz-Moreno, Anna M Hätälä, Katharina M Rolfes, Ismael Sánchez-Vera, Joan Gil, Elies Molins, Antonio Viayna, Alexander Hanzl, Nicolas H Thomä, Thomas Haarmann-Stemmann, F Javier Luque, Rodolfo Lavilla, Ouldouz Ghashghaei","doi":"10.1021/acscentsci.5c00194","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00194","url":null,"abstract":"A multidisciplinary platform is presented to address aryl hydrocarbon receptor (AhR) modulation. A rewired Yonemitsu multicomponent reaction with indole 2-carboxaldehydes and nucleophilic species was designed to access a family of 6-substituted indolocarbazoles. The conformational behavior of these compounds was examined to rationalize their axial chirality. In silico docking and molecular simulations highlighted key features implicated in their binding to AhR. Furthermore, the synthesis of linkable derivatives allowed the direct development of conjugated entities. Reporter gene and target gene expression analyses identified these novel structures as potent noncytotoxic activating AhR ligands, that can be extended to bifunctional molecules. The anti-inflammatory properties of these AhR agonists were assessed in interleukin-13 treated keratinocytes. Altogether, the synergistic research in synthetic and computational chemistry integrated with biological studies opens novel avenues toward understanding the biological roles of AhR and the development of targeted therapeutics.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"629-641"},"PeriodicalIF":12.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Multicomponent Reaction-Based Platform Opens New Avenues in Aryl Hydrocarbon Receptor Modulation 基于多组分反应的平台为芳基烃受体调节开辟了新途径

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-04-10 DOI: 10.1021/acscentsci.5c0019410.1021/acscentsci.5c00194

Pau Nadal Rodríguez, Frederick Hartung, Marina Pedrola, Seemon Coomar, Alejandro Diaz-Moreno, Anna M. Hätälä, Katharina M. Rolfes, Ismael Sánchez-Vera, Joan Gil, Elies Molins, Antonio Viayna, Alexander Hanzl, Nicolas H. Thomä, Thomas Haarmann-Stemmann*, F. Javier Luque*, Rodolfo Lavilla* and Ouldouz Ghashghaei*,

{"title":"A Multicomponent Reaction-Based Platform Opens New Avenues in Aryl Hydrocarbon Receptor Modulation","authors":"Pau Nadal Rodríguez, Frederick Hartung, Marina Pedrola, Seemon Coomar, Alejandro Diaz-Moreno, Anna M. Hätälä, Katharina M. Rolfes, Ismael Sánchez-Vera, Joan Gil, Elies Molins, Antonio Viayna, Alexander Hanzl, Nicolas H. Thomä, Thomas Haarmann-Stemmann*, F. Javier Luque*, Rodolfo Lavilla* and Ouldouz Ghashghaei*, ","doi":"10.1021/acscentsci.5c0019410.1021/acscentsci.5c00194","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00194https://doi.org/10.1021/acscentsci.5c00194","url":null,"abstract":"A multidisciplinary platform is presented to address aryl hydrocarbon receptor (AhR) modulation. A rewired Yonemitsu multicomponent reaction with indole 2-carboxaldehydes and nucleophilic species was designed to access a family of 6-substituted indolocarbazoles. The conformational behavior of these compounds was examined to rationalize their axial chirality. In silico docking and molecular simulations highlighted key features implicated in their binding to AhR. Furthermore, the synthesis of linkable derivatives allowed the direct development of conjugated entities. Reporter gene and target gene expression analyses identified these novel structures as potent noncytotoxic activating AhR ligands, that can be extended to bifunctional molecules. The anti-inflammatory properties of these AhR agonists were assessed in interleukin-13 treated keratinocytes. Altogether, the synergistic research in synthetic and computational chemistry integrated with biological studies opens novel avenues toward understanding the biological roles of AhR and the development of targeted therapeutics.A multicomponent reaction platform yields 6-substituted indolocarbazoles as potent, safe, and modular activators of the Aryl hydrocarbon Receptor (AhR), opening new avenues in AhR research.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"629–641 629–641"},"PeriodicalIF":12.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0