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LA-ICP-TOFMS Imaging Reveals Significant Influence of Cancer Cell Resistance on Oxaliplatin Compartmentalization in the Tumor Microenvironment. LA-ICP-TOFMS成像揭示肿瘤微环境中癌细胞耐药对奥沙利铂区隔化的显著影响
IF 8.5
JACS Au Pub Date : 2025-06-11 eCollection Date: 2025-06-23 DOI: 10.1021/jacsau.5c00217
Martin Schaier, Dina Baier, Sarah Theiner, Walter Berger, Gunda Koellensperger
{"title":"LA-ICP-TOFMS Imaging Reveals Significant Influence of Cancer Cell Resistance on Oxaliplatin Compartmentalization in the Tumor Microenvironment.","authors":"Martin Schaier, Dina Baier, Sarah Theiner, Walter Berger, Gunda Koellensperger","doi":"10.1021/jacsau.5c00217","DOIUrl":"10.1021/jacsau.5c00217","url":null,"abstract":"<p><p>Chemoresistance in cancer cells, particularly in refractory types, such as colorectal cancer, poses a major challenge to effective treatment. In particular, the interaction between cancer cells and the tumor microenvironment (TME) has been shown to exert substantial influence on the efficacy of therapeutic agents. This study investigated whether an intrinsic resistance phenotype alters drug distribution in the TME using xenograft models derived from HCT116 colorectal cancer cells, including oxaliplatin (OxPt)-sensitive and OxPt-resistant (OxR) variants. Tumors were prepared as formalin-fixed paraffin-embedded (FFPE) sections, followed by single-cell analysis with laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS). Based on histological evaluations, a panel of metal-conjugated antibodies was designed to target tissue architecture and distinct cell states within the TME. A dedicated calibration strategy was applied to accurately measure platinum (Pt) uptake in phenotypically defined single cells across both the tumor and its microenvironment. The results revealed substantial structural differences: HCT116/OxR tumors exhibited robust growth following drug administration, while parental tumors displayed extensive degradation. Notably, OxPt accumulated significantly in necrotic regions specific to HCT116/OxR, indicating resistance-dependent changes in drug compartmentalization. These findings suggest that an intrinsically resistant cancer cell phenotype is capable of markedly altering metal distributions within the TME.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2619-2631"},"PeriodicalIF":8.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fundamental Role of N-O Bond-Containing Compounds in Prebiotic Synthesis. 含N-O键化合物在益生元合成中的基本作用。
IF 8.5
JACS Au Pub Date : 2025-06-10 eCollection Date: 2025-06-23 DOI: 10.1021/jacsau.5c00334
Alexey Yu Sukhorukov
{"title":"Fundamental Role of N-O Bond-Containing Compounds in Prebiotic Synthesis.","authors":"Alexey Yu Sukhorukov","doi":"10.1021/jacsau.5c00334","DOIUrl":"10.1021/jacsau.5c00334","url":null,"abstract":"<p><p>The emergence of biomolecules on the primordial Earth represents a pivotal scientific question for understanding the origin of life. Recent studies show that compounds containing nitrogen-oxygen bonds could serve as important feedstocks in prebiotic synthesis and intermediates in primitive metabolic pathways. Simple N-O-compounds have been identified in the interstellar medium and were likely formed from molecular nitrogen in the early Earth's atmosphere in the course of high-energy events. N-O-compounds are reactive species with rich chemistry enabling abiotic nitrogen fixation processes. Moreover, various inorganic and organic N-O-compounds are produced and used by modern organisms suggesting these species could play a crucial role at certain stages in the emergence and evolution of life. In this perspective, the potential role of N-O bond-containing compounds as fundamental building blocks and intermediates in prebiotic synthesis is summarized and discussed in a broad context (from simple nitrogen oxides to complicated organic N-O bearing molecules). In the first section, experimental and theoretical data on the detection, formation, and processing of simple N-O-compounds in space is considered. The second section focuses on the abiotic synthesis of N-O-compounds via chemical and photochemical reactions in the primordial atmosphere and ocean. The last two sections deal with the state-of-the-art laboratory-designed chemical reaction networks producing amino acids, peptides, and nucleosides from N-O compounds under prebiotically plausible conditions.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2420-2442"},"PeriodicalIF":8.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leveraging the Aminothiol-Specific Phosphorogenic Response of Iridium(III) Thioester Complexes for the Development of Intracellular Sensors and Cancer Phototherapeutics 利用铱(III)硫酯配合物的氨基硫醇特异性产磷反应开发细胞内传感器和癌症光疗
IF 8.5
JACS Au Pub Date : 2025-06-10 DOI: 10.1021/jacsau.5c0041310.1021/jacsau.5c00413
Eunice Chiu-Lam Mak, Ziyong Chen, Lawrence Cho-Cheung Lee, Liang-Liang Yan, Vivian Wing-Wah Yam* and Kenneth Kam-Wing Lo*, 
{"title":"Leveraging the Aminothiol-Specific Phosphorogenic Response of Iridium(III) Thioester Complexes for the Development of Intracellular Sensors and Cancer Phototherapeutics","authors":"Eunice Chiu-Lam Mak,&nbsp;Ziyong Chen,&nbsp;Lawrence Cho-Cheung Lee,&nbsp;Liang-Liang Yan,&nbsp;Vivian Wing-Wah Yam* and Kenneth Kam-Wing Lo*,&nbsp;","doi":"10.1021/jacsau.5c0041310.1021/jacsau.5c00413","DOIUrl":"https://doi.org/10.1021/jacsau.5c00413https://doi.org/10.1021/jacsau.5c00413","url":null,"abstract":"<p >Site-specific bioconjugation techniques are extensively utilized in biological and biomedical fields to precisely label biomolecules with luminescent tags for direct visualization of their intracellular dynamics or with cytotoxic agents for the development of novel anticancer therapeutics. In this work, a series of cyclometalated iridium(III) polypyridine complexes featuring a thioester moiety was designed as novel phosphorogenic probes for labeling N-terminal cysteine (N-Cys)-containing biomolecules. These thioester complexes were weakly emissive in solutions due to the presence of a low-lying nonradiative distorted triplet intraligand (<sup>3</sup>IL) state localized on the thioester unit, as elucidated by computational analyses. However, their emission intensities and singlet oxygen (<sup>1</sup>O<sub>2</sub>)-photosensitization efficiencies substantially increased upon reaction with <span>l</span>-Cys due to the conversion of the quenching thioester moiety to a nonquenching amide unit. Additionally, the thioester complexes exhibited high selectivity toward N-Cys and displayed significantly enhanced reactivity due to the electron-withdrawing iridium(III) polypyridine moiety. The remarkable aminothiol-induced emission and <sup>1</sup>O<sub>2</sub>-photosensitization turn-on of the thioester complexes were exploited for the development of intracellular Cys sensors and Cys-activatable photosensitizers for cancer-targeted photodynamic therapy. Furthermore, one of the thioester complexes was selected to react with various N-Cys-modified tumor-targeting peptides, yielding photofunctional iridium(III)–peptide conjugates with high <sup>1</sup>O<sub>2</sub> generation efficiencies. These conjugates retained the tumor-targeting capabilities of the original peptides and showed high specificity for MDA-MB-231 cells compared to MCF-7 and HEK-293 cells, resulting in selective photocytotoxicity toward this triple-negative breast cancer cell line. We believe that our design approach will inspire the development of novel luminogenic thioester-based reagents for bioconjugation, bioimaging, and therapeutic applications.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2825–2836 2825–2836"},"PeriodicalIF":8.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fundamental Role of N–O Bond-Containing Compounds in Prebiotic Synthesis 含N-O键化合物在益生元合成中的基本作用
IF 8.5
JACS Au Pub Date : 2025-06-10 DOI: 10.1021/jacsau.5c0033410.1021/jacsau.5c00334
Alexey Yu. Sukhorukov*, 
{"title":"Fundamental Role of N–O Bond-Containing Compounds in Prebiotic Synthesis","authors":"Alexey Yu. Sukhorukov*,&nbsp;","doi":"10.1021/jacsau.5c0033410.1021/jacsau.5c00334","DOIUrl":"https://doi.org/10.1021/jacsau.5c00334https://doi.org/10.1021/jacsau.5c00334","url":null,"abstract":"<p >The emergence of biomolecules on the primordial Earth represents a pivotal scientific question for understanding the origin of life. Recent studies show that compounds containing nitrogen–oxygen bonds could serve as important feedstocks in prebiotic synthesis and intermediates in primitive metabolic pathways. Simple N–O-compounds have been identified in the interstellar medium and were likely formed from molecular nitrogen in the early Earth’s atmosphere in the course of high-energy events. N–O-compounds are reactive species with rich chemistry enabling abiotic nitrogen fixation processes. Moreover, various inorganic and organic N–O-compounds are produced and used by modern organisms suggesting these species could play a crucial role at certain stages in the emergence and evolution of life. In this perspective, the potential role of N–O bond-containing compounds as fundamental building blocks and intermediates in prebiotic synthesis is summarized and discussed in a broad context (from simple nitrogen oxides to complicated organic N–O bearing molecules). In the first section, experimental and theoretical data on the detection, formation, and processing of simple N–O-compounds in space is considered. The second section focuses on the abiotic synthesis of N–O-compounds via chemical and photochemical reactions in the primordial atmosphere and ocean. The last two sections deal with the state-of-the-art laboratory-designed chemical reaction networks producing amino acids, peptides, and nucleosides from N–O compounds under prebiotically plausible conditions.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2420–2442 2420–2442"},"PeriodicalIF":8.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leveraging the Aminothiol-Specific Phosphorogenic Response of Iridium(III) Thioester Complexes for the Development of Intracellular Sensors and Cancer Phototherapeutics. 利用铱(III)硫酯配合物的氨基硫醇特异性产磷反应开发细胞内传感器和癌症光疗。
IF 8.5
JACS Au Pub Date : 2025-06-10 eCollection Date: 2025-06-23 DOI: 10.1021/jacsau.5c00413
Eunice Chiu-Lam Mak, Ziyong Chen, Lawrence Cho-Cheung Lee, Liang-Liang Yan, Vivian Wing-Wah Yam, Kenneth Kam-Wing Lo
{"title":"Leveraging the Aminothiol-Specific Phosphorogenic Response of Iridium(III) Thioester Complexes for the Development of Intracellular Sensors and Cancer Phototherapeutics.","authors":"Eunice Chiu-Lam Mak, Ziyong Chen, Lawrence Cho-Cheung Lee, Liang-Liang Yan, Vivian Wing-Wah Yam, Kenneth Kam-Wing Lo","doi":"10.1021/jacsau.5c00413","DOIUrl":"10.1021/jacsau.5c00413","url":null,"abstract":"<p><p>Site-specific bioconjugation techniques are extensively utilized in biological and biomedical fields to precisely label biomolecules with luminescent tags for direct visualization of their intracellular dynamics or with cytotoxic agents for the development of novel anticancer therapeutics. In this work, a series of cyclometalated iridium-(III) polypyridine complexes featuring a thioester moiety was designed as novel phosphorogenic probes for labeling N-terminal cysteine (N-Cys)-containing biomolecules. These thioester complexes were weakly emissive in solutions due to the presence of a low-lying nonradiative distorted triplet intraligand (<sup>3</sup>IL) state localized on the thioester unit, as elucidated by computational analyses. However, their emission intensities and singlet oxygen (<sup>1</sup>O<sub>2</sub>)-photosensitization efficiencies substantially increased upon reaction with l-Cys due to the conversion of the quenching thioester moiety to a nonquenching amide unit. Additionally, the thioester complexes exhibited high selectivity toward N-Cys and displayed significantly enhanced reactivity due to the electron-withdrawing iridium-(III) polypyridine moiety. The remarkable aminothiol-induced emission and <sup>1</sup>O<sub>2</sub>-photosensitization turn-on of the thioester complexes were exploited for the development of intracellular Cys sensors and Cys-activatable photosensitizers for cancer-targeted photodynamic therapy. Furthermore, one of the thioester complexes was selected to react with various N-Cys-modified tumor-targeting peptides, yielding photofunctional iridium-(III)-peptide conjugates with high <sup>1</sup>O<sub>2</sub> generation efficiencies. These conjugates retained the tumor-targeting capabilities of the original peptides and showed high specificity for MDA-MB-231 cells compared to MCF-7 and HEK-293 cells, resulting in selective photocytotoxicity toward this triple-negative breast cancer cell line. We believe that our design approach will inspire the development of novel luminogenic thioester-based reagents for bioconjugation, bioimaging, and therapeutic applications.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2825-2836"},"PeriodicalIF":8.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unconventional Ring Opening Triggers Intramolecular C-H Amination of Anthranils via Electrocyclization under Cobalt Catalysis. 非常规开环触发分子内C-H胺化在钴催化下的电环化。
IF 8.5
JACS Au Pub Date : 2025-06-10 eCollection Date: 2025-06-23 DOI: 10.1021/jacsau.5c00281
Yogesh N Aher, Susovon Ghosh, Bhaskar Mondal, Amit B Pawar
{"title":"Unconventional Ring Opening Triggers Intramolecular C-H Amination of Anthranils via Electrocyclization under Cobalt Catalysis.","authors":"Yogesh N Aher, Susovon Ghosh, Bhaskar Mondal, Amit B Pawar","doi":"10.1021/jacsau.5c00281","DOIUrl":"10.1021/jacsau.5c00281","url":null,"abstract":"<p><p>Transition metal-catalyzed anthranil ring opening offers a robust and versatile approach for constructing a wide range of nitrogen-containing heterocycles. Here, we report an unprecedented ring opening of anthranil that triggers its intramolecular C-H amination through an electrocyclization pathway. This novel mechanistic approach enabled the first Cp*Co-(III)-catalyzed intramolecular C-H amination of anthranils utilizing C7 aryl/alkenyl-substituted congeners to access carbazoles and indoles under redox-neutral conditions. The mechanistic and computational investigation revealed that anthranil derivatives undergo \"unconventional\" ring opening facilitated by electron donation from the aryl ring at the C7 position to form a unique cobalt-nitrenoid species, which follows an electrocyclization pathway to achieve the intramolecular C-H amination. The \"true\" electronic nature of the Co-nitrenoid species has been revealed through meticulous electronic structure analysis. The developed synthetic protocol is 100% atom-economic, ensuring no byproduct formation while maintaining exceptional efficiency. Notably, the reaction demonstrated remarkable regioselectivity, preferentially yielding the carbazole derivative over the acridone derivative. Moreover, we showcased the synthetic versatility of the synthesized carbazole derivative through successful formyl C-H amidation and arylation reactions.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2677-2688"},"PeriodicalIF":8.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Photoactive Neutral Three-Coordinate Cu(I) Complexes of Anionic N-Heterocyclic Carbenes 阴离子n -杂环碳烯的光活性中性三配位Cu(I)配合物
IF 8.5
JACS Au Pub Date : 2025-06-09 DOI: 10.1021/jacsau.5c0035710.1021/jacsau.5c00357
Lars E. Burmeister, Lucie J. Groth, Philipp R. Meinhold, Johannes P. Zurwellen, Dirk Bockfeld, René Frank, Michael Karnahl, Matthias Tamm* and Stefanie Tschierlei*, 
{"title":"Photoactive Neutral Three-Coordinate Cu(I) Complexes of Anionic N-Heterocyclic Carbenes","authors":"Lars E. Burmeister,&nbsp;Lucie J. Groth,&nbsp;Philipp R. Meinhold,&nbsp;Johannes P. Zurwellen,&nbsp;Dirk Bockfeld,&nbsp;René Frank,&nbsp;Michael Karnahl,&nbsp;Matthias Tamm* and Stefanie Tschierlei*,&nbsp;","doi":"10.1021/jacsau.5c0035710.1021/jacsau.5c00357","DOIUrl":"https://doi.org/10.1021/jacsau.5c00357https://doi.org/10.1021/jacsau.5c00357","url":null,"abstract":"<p >Three-coordinate Cu(I) complexes are promising candidates for photoactive compounds, but their application in photocatalysis remains largely unexplored. Here, we report the synthesis and comprehensive characterization of four novel three-coordinate Cu(I) complexes featuring an anionic N-heterocyclic carbene ligand with a weakly coordinating tris(pentafluorophenyl)borate moiety (WCA-NHC) and different methyl substituted dipyridylamine-based N,N′-ligands. This ligand design significantly improves the stability and photophysical properties of these complexes in solution. Steady-state and time-resolved spectroscopy, electrochemical measurements, temperature-dependent emission studies and quantum chemical calculations were used to elucidate the electronic and excited-state properties of these complexes. Our results demonstrate metal-to-ligand charge transfer absorption and thermally activated delayed fluorescence (TADF), leading to extended excited-state lifetimes (up to 8.6 μs) and high excited-state energies (≈2.7 eV). All four complexes efficiently photosensitize the norbornadiene-to-quadricyclane photoisomerization, a key reaction for molecular solar thermal energy storage (MOST). By demonstrating that careful ligand selection allows the design of three-coordinate Cu(I) complexes with excellent photophysical and photocatalytic properties, this study expands the scope of Cu(I) photosensitizers and lays the foundation for further applications in photochemistry.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2792–2801 2792–2801"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phosphonium Ylide as Hydrogen Atom Transfer Catalyst Platform Based on Carbon-Centered Radical with High Structural Tunability 基于高结构可调性碳中心自由基的氢化磷转移催化剂平台
IF 8.5
JACS Au Pub Date : 2025-06-09 DOI: 10.1021/jacsau.5c0040010.1021/jacsau.5c00400
Joaquim Caner, Natsumi Maeda, Daisuke Yokogawa, Akira Matsumoto* and Keiji Maruoka*, 
{"title":"Phosphonium Ylide as Hydrogen Atom Transfer Catalyst Platform Based on Carbon-Centered Radical with High Structural Tunability","authors":"Joaquim Caner,&nbsp;Natsumi Maeda,&nbsp;Daisuke Yokogawa,&nbsp;Akira Matsumoto* and Keiji Maruoka*,&nbsp;","doi":"10.1021/jacsau.5c0040010.1021/jacsau.5c00400","DOIUrl":"https://doi.org/10.1021/jacsau.5c00400https://doi.org/10.1021/jacsau.5c00400","url":null,"abstract":"<p >Hydrogen atom transfer (HAT) catalysis has emerged as a powerful tool for the C–H functionalization of organic molecules. While several HAT catalysts based on heteroatom-centered radicals have been developed, the study of the catalytic use of carbon-centered radicals responsible for the HAT process has been underexplored. Herein, we introduce phosphonium ylides as a HAT catalyst platform based on a carbon-centered radical. The readily available and highly tunable features of this platform have allowed the systematic study of the effect of the catalyst structure on its physical properties. The ability of these ylides as practical HAT catalysts has been demonstrated in the photoinduced C–H alkylation of various small organic molecules, including alcohols, heterocycles, and primary amines.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2463–2468 2463–2468"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unconventional Ring Opening Triggers Intramolecular C–H Amination of Anthranils via Electrocyclization under Cobalt Catalysis 非常规开环触发分子内C-H胺化在钴催化下的电环化
IF 8.5
JACS Au Pub Date : 2025-06-09 DOI: 10.1021/jacsau.5c0028110.1021/jacsau.5c00281
Yogesh N. Aher, Susovon Ghosh, Bhaskar Mondal* and Amit B. Pawar*, 
{"title":"Unconventional Ring Opening Triggers Intramolecular C–H Amination of Anthranils via Electrocyclization under Cobalt Catalysis","authors":"Yogesh N. Aher,&nbsp;Susovon Ghosh,&nbsp;Bhaskar Mondal* and Amit B. Pawar*,&nbsp;","doi":"10.1021/jacsau.5c0028110.1021/jacsau.5c00281","DOIUrl":"https://doi.org/10.1021/jacsau.5c00281https://doi.org/10.1021/jacsau.5c00281","url":null,"abstract":"<p >Transition metal-catalyzed anthranil ring opening offers a robust and versatile approach for constructing a wide range of nitrogen-containing heterocycles. Here, we report an unprecedented ring opening of anthranil that triggers its intramolecular C–H amination through an electrocyclization pathway. This novel mechanistic approach enabled the first Cp*Co(III)-catalyzed intramolecular C–H amination of anthranils utilizing C7 aryl/alkenyl-substituted congeners to access carbazoles and indoles under redox-neutral conditions. The mechanistic and computational investigation revealed that anthranil derivatives undergo “unconventional” ring opening facilitated by electron donation from the aryl ring at the C7 position to form a unique cobalt-nitrenoid species, which follows an electrocyclization pathway to achieve the intramolecular C–H amination. The “true” electronic nature of the Co-nitrenoid species has been revealed through meticulous electronic structure analysis. The developed synthetic protocol is 100% atom-economic, ensuring no byproduct formation while maintaining exceptional efficiency. Notably, the reaction demonstrated remarkable regioselectivity, preferentially yielding the carbazole derivative over the acridone derivative. Moreover, we showcased the synthetic versatility of the synthesized carbazole derivative through successful formyl C–H amidation and arylation reactions.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2677–2688 2677–2688"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-Fidelity, One-Pot Nucleic Acid Amplification via OMEGA IsrB Nickase Cycling for Clinical Pathogen Detection OMEGA IsrB镍酶循环高保真一锅核酸扩增技术用于临床病原体检测
IF 8.5
JACS Au Pub Date : 2025-06-09 DOI: 10.1021/jacsau.5c0037910.1021/jacsau.5c00379
Yusheng Liao, Yifan Sun, Hui Yu, Jiali Ren* and Fengjiao He*, 
{"title":"High-Fidelity, One-Pot Nucleic Acid Amplification via OMEGA IsrB Nickase Cycling for Clinical Pathogen Detection","authors":"Yusheng Liao,&nbsp;Yifan Sun,&nbsp;Hui Yu,&nbsp;Jiali Ren* and Fengjiao He*,&nbsp;","doi":"10.1021/jacsau.5c0037910.1021/jacsau.5c00379","DOIUrl":"https://doi.org/10.1021/jacsau.5c00379https://doi.org/10.1021/jacsau.5c00379","url":null,"abstract":"<p >Nucleic acid amplification technologies are pivotal in diagnostics but face challenges from nonspecific amplification and inefficient proofreading. CRISPR-based methods are hindered by persistent protein occupation postcleavage, limiting scalability. Here, we present an OMEGA IsrB Nickase Cyclic Exponential (ONCE) amplification, a novel isothermal strategy leveraging the RNA-guided nickase IsrB for site-specific proofreading. ONCE uniquely integrates DNA polymerase to cyclically displace IsrB from target sites, enabling high-fidelity, one-pot exponential amplification. Systematic validation demonstrates attomolar sensitivity and single-nucleotide mismatch discrimination, outperforming those of CRISPR-Cas9 and conventional nickases. Applied to bacterial detection, ONCE quantifies <i>Pseudomonas aeruginosa</i> at 4.16 CFU/mL within 70 min, achieving 94.12% sensitivity and 100% specificity in clinical urine samples with no false-positives compared to qPCR. This work establishes ONCE as a robust, scalable tool for precision diagnostics in clinical and point-of-care settings.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2802–2809 2802–2809"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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