IF 8.7

JACS Au Pub Date : 2025-08-27 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00522

Mingyu Luo, Linya Xu, Xin Gao, Chun-Ming Chan, Qiushi Shen, Bingnan Du, Wing-Yiu Yu

{"title":"Ni-Catalyzed Distal-Selective gem-Difluorovinylation of Unactivated Alkenes with 2,2-Difluorovinyl Benzoates.","authors":"Mingyu Luo, Linya Xu, Xin Gao, Chun-Ming Chan, Qiushi Shen, Bingnan Du, Wing-Yiu Yu","doi":"10.1021/jacsau.5c00522","DOIUrl":"10.1021/jacsau.5c00522","url":null,"abstract":"The gem-difluoroalkene is a bioisostere of the carbonyl group, used for improving the bioavailability of drug candidates. Here, we present an intermolecular Ni-catalyzed strategy for the distal-selective hydro gem-difluorovinylation of unactivated alkenes, utilizing 2,2-difluorovinyl benzoates (BzO-DFs) as building blocks for the synthesis of a wide array of gem-difluoroenol ethers that are otherwise challenging to produce. Diverse BzO-DF derivatives bearing sensitive functional groups, strained carbocycles, and natural products are prepared from inexpensive bromodifluoroacetates by using metallic zinc as a reductant. The cross-coupling reaction is initiated by Ni(0) oxidative addition to BzO-DFs to form the difluorovinyl Ni-(II) complexes as the resting state. The vinyl Ni-(II) complexes have been characterized by ESI-MS. The precoordination of the picolinimide auxiliary facilitates the migratory insertion of the difluorovinyl Ni-(II) into alkenes, exhibiting exceptional regiocontrol and broad functional group tolerance. Complementary to the methods involving organometallic nucleophiles, this approach employs alkenes as abundant nucleophiles, achieving high distal-selectivity without chain-walked isomerization. The synthetic utility is further demonstrated through late-stage modifications with complex, medicinally relevant molecules.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4224-4232"},"PeriodicalIF":8.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152351","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

Ru(II) Complex-Mediated Phase Separation Amplifies Photocatalytic RNA Damage to Stimulate RIG‑I Immunotherapy. Ru（II）络合物介导的相分离放大光催化RNA损伤以刺激RIG - I免疫治疗。

IF 8.7

JACS Au Pub Date : 2025-08-27 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00867

Xiao-Xiao Chen, Xia Mu, Zhi-Yuan Li, Kun Peng, Qing-Hua Shen, Yue-Bin Zhang, Cai-Ping Tan

{"title":"Ru(II) Complex-Mediated Phase Separation Amplifies Photocatalytic RNA Damage to Stimulate RIG‑I Immunotherapy.","authors":"Xiao-Xiao Chen, Xia Mu, Zhi-Yuan Li, Kun Peng, Qing-Hua Shen, Yue-Bin Zhang, Cai-Ping Tan","doi":"10.1021/jacsau.5c00867","DOIUrl":"10.1021/jacsau.5c00867","url":null,"abstract":"Phase separation is closely related to the transcription, processing, translation, and metabolism of RNA, and regulating RNA phase separation may serve as an effective antitumor strategy. However, small molecule-based RNA phase separation inducers have not yet been reported. Herein, based on our previous work, we designed a Ru-(II) complex (Ru1) that can form multivalent interactions with RNA and induce the phase separation of both double-stranded RNA (dsRNA) and single-stranded RNA (ssRNA) in vitro. Interestingly, the substituents on the ligands, including the positively charged triphenylphosphine and the hydroxyl groups, play decisive roles in its capability to induce RNA phase separation, which is also confirmed by molecular dynamics simulations. Moreover, Ru1-mediated phase separation preceding photoactivation establishes a novel RNA-centric immune activation mechanism, wherein subsequent photodamage to RNA triggers the retinoic-acid-inducible gene I (RIG-I) pathway. Finally, we demonstrate that Ru1 can significantly improve tumor immune microenvironments.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4547-4559"},"PeriodicalIF":8.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208760","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

Directed Evolution of Nonheme Iron Enzymes for Enantioselective Aminative Difunctionalization of Alkenes. 烯烃对映选择性胺双官能化非血红素铁酶的定向进化。

IF 8.7

JACS Au Pub Date : 2025-08-27 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00817

Fei Liu, Si-Yi Li, Zi-Shan Fan, Jia-Hua Luo, Xue Zeng, Long Wei, Ye Li, Jia-Yao Li, Yongxiang Zheng, Xin Wang, Chun Zhang, Peng Chen, Zhi-Jun Jia

引用次数: 0

Direct Observation of the Conformational Transitions in Tau and Their Correlation with Phase Behavior. Tau中构象转变的直接观察及其与相行为的关系。

IF 8.7

JACS Au Pub Date : 2025-08-26 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00625

Jitao Wen, Yiming Tang, Tomas Sneideris, Hannes Ausserwöger, Liu Hong, Tuomas P J Knowles, Sarah Perrett, Guanghong Wei, Si Wu

{"title":"Direct Observation of the Conformational Transitions in Tau and Their Correlation with Phase Behavior.","authors":"Jitao Wen, Yiming Tang, Tomas Sneideris, Hannes Ausserwöger, Liu Hong, Tuomas P J Knowles, Sarah Perrett, Guanghong Wei, Si Wu","doi":"10.1021/jacsau.5c00625","DOIUrl":"10.1021/jacsau.5c00625","url":null,"abstract":"Liquid-liquid phase separation (LLPS) is now recognized as one of the key mechanisms underlying the formation of membraneless organelles. Typically, condensates formed through LLPS are dynamic and play a crucial role in the spatiotemporal regulation of essential cellular processes. In some cases, however, condensates can undergo an aberrant liquid-to-solid transition, which is now recognized as being related to the onset of cancers and neurodegeneration. The microtubule-associated protein Tau, the aberrant aggregation of which is implicated in neurodegenerative disorders like Alzheimer's and Parkinson's, has been found to undergo LLPS. The Tau condensates formed through LLPS are considered to be intermediate on-pathway precursors of amyloid aggregates. Unlike other known phase-separating proteins (e.g., FUS or TDP-43) that have low-complexity domains (LCDs), Tau is intrinsically disordered. Thus, Tau exhibits a highly flexible structure that can be modulated by changes in environmental changes. The intricate relationship between different conformations of full-length Tau and its phase behavior remains poorly understood. To bridge this gap, here, by employing a combination of single-molecule FRET and molecular dynamics simulations, we demonstrate that Tau undergoes conformational transitions from compact to extended states during LLPS, irrespective of diverse driving forces. Moreover, we show that intramolecular interactions responsible for stabilizing the compact conformations of monomeric Tau correlate with the intermolecular interactions driving the LLPS of Tau, thereby facilitating the formation of dynamic networks. These findings provide crucial mechanistic insights into how the conformational state of Tau governs its propensity for phase separation, shedding light on sequence-encoded structural processes that ultimately drive biological phase separation.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4268-4280"},"PeriodicalIF":8.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152395","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

Synthesis of Anhydro-dc-Tetracyclic Saxitoxin Via a Photoinduced Cycloaddition. 光诱导环加成法合成无水dc-四环蛤蚌毒素。

IF 8.7

JACS Au Pub Date : 2025-08-26 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c01028

Runting Fang, Yang Jiao, Tianrun Xia, Jiaqi Liu, Tuoping Luo

引用次数: 0

Bioinspired Synthesis of Bridged Isochromane Fused Pyrazoles by a Silver Catalyzed Cascade Reaction and Its Application for Antibacterial Activity. 银催化级联反应合成桥接等铬胺融合吡唑及其抗菌活性研究。

IF 8.7

JACS Au Pub Date : 2025-08-26 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00105

Bhuvnesh Singh, Shreya Tewari, Manleen Kaur, Himanshu Sharma, Kumar Vanka, Neetu Singh, Ravi P Singh

引用次数: 0

The Role of Structural Dispersity of Polymer Brushes in Determining the Colloidal Stability of Core-Shell Nanoparticles and Their Interaction with Anti-PEG Antibodies. 聚合物刷的结构分散性在决定核壳纳米颗粒胶体稳定性及其与抗peg抗体的相互作用中的作用。

IF 8.7

JACS Au Pub Date : 2025-08-26 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00852

Carlos Pavón, Antonella Grigoletto, Verena Kempkes, Ander Eguskiza, Maria Morbidelli, Roberto Fiammengo, Emanuele Papini, Andrea Mattarei, Gianfranco Pasut, Krzysztof Matyjaszewski, Francesca Lorandi, Edmondo M Benetti

{"title":"The Role of Structural Dispersity of Polymer Brushes in Determining the Colloidal Stability of Core-Shell Nanoparticles and Their Interaction with Anti-PEG Antibodies.","authors":"Carlos Pavón, Antonella Grigoletto, Verena Kempkes, Ander Eguskiza, Maria Morbidelli, Roberto Fiammengo, Emanuele Papini, Andrea Mattarei, Gianfranco Pasut, Krzysztof Matyjaszewski, Francesca Lorandi, Edmondo M Benetti","doi":"10.1021/jacsau.5c00852","DOIUrl":"10.1021/jacsau.5c00852","url":null,"abstract":"The structural dispersity of poly-[oligo-(ethylene glycol) methacrylate] (POEGMA) brushes critically influences the stabilization of Au nanoparticles (NPs) and their interactions with anti-PEG antibodies (APAs). Commercial oligo-(ethylene glycol) methacrylate (OEG p MA) macromonomers are intrinsically polydisperse, featuring a distribution of ethylene glycol (EG) units spanning from n = 2 to n = 15. Flash chromatography was applied to isolate OEG 8 MA with discrete length (n = 8)the most abundant species in commercial mixtures. Controlled radical polymerization of polydisperse and discrete monomer sources was subsequently applied to generate POEG p MA and POEG 8 MA, which feature heterogeneous and homogeneous structures, respectively, while displaying an overall identical composition. When used to form shells on Au NPs, uniform POEG 8 MA brushes provided enhanced colloidal stability across a wide temperature range compared to their polydisperse counterparts. While serum protein corona formation was largely determined by polymer composition, APA binding was promoted by longer OEG segments present in polydisperse POEG p MA shells, which acted as epitopes for antibody recognition. These findings highlight how controlling polymer architecture and dispersity in the design of PEG-based shells for NPs could give access to nonimmunogenic formulations. More broadly, polymer dispersity emerges as an additional tool for modulating the behavior of nanomaterials within biological systems.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4519-4529"},"PeriodicalIF":8.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152440","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

Advances in Small Molecule Activation Toward Sustainable Chemical Transformations 面向可持续化学转化的小分子活化研究进展

IF 8.7

JACS Au Pub Date : 2025-08-25 DOI: 10.1021/jacsau.5c00935

Christian Limberg, Jaeheung Cho and Carole Duboc*,

引用次数: 0

fac-Re(2,2'-bipyridine)(CO)₃Cl Catalyzes Visible-Light-Driven Functionalization of an Organic Substrate with CO₂. 面- re（2,2′-联吡啶）（CO）3Cl催化CO2催化有机底物的可见光功能化

IF 8.7

JACS Au Pub Date : 2025-08-25 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00665

Phurinat Lorwongkamol, Taito Watanabe, Masaki Kitada, Yuta Uetake, Yutaka Saga, Tetsuya Kambe, Mio Kondo, Shigeyuki Masaoka

{"title":"fac-Re(2,2'-bipyridine)(CO)3Cl Catalyzes Visible-Light-Driven Functionalization of an Organic Substrate with CO2.","authors":"Phurinat Lorwongkamol, Taito Watanabe, Masaki Kitada, Yuta Uetake, Yutaka Saga, Tetsuya Kambe, Mio Kondo, Shigeyuki Masaoka","doi":"10.1021/jacsau.5c00665","DOIUrl":"10.1021/jacsau.5c00665","url":null,"abstract":"The molecular photocatalyst fac-Re-(2,2'-bipyridine)-(CO)3Cl ([Re-Cl]) is well established and has been extensively investigated for the highly active and selective conversion of CO2 to CO. However, its reactivity in processes other than CO2 reduction has rarely been explored. Herein, we report the application of [Re-Cl] as a catalyst for the visible-light-driven carboxylation of an alkene using CO2, with phenyl vinyl sulfone (1) serving as a model substrate. The catalytic system successfully catalyzed the carboxylation of 1 to its corresponding carboxylic acid, with complete suppression of CO formation throughout the reaction. A turnover number (TON) of up to 2600, along with excellent regioselectivity, was achieved under optimized conditions. Control experiments revealed the key role of each reaction component, while isotope labeling with 13CO2 confirmed that the carboxyl group originated from CO2. Furthermore, mechanistic investigations suggested that the Re-CO2 intermediate reacts directly with the alkene. These findings highlight the potential of Re-based molecular complexes for broader reactivities and expand their applicability in sustainable synthetic transformations.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4170-4177"},"PeriodicalIF":8.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152341","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

Multicomponent Reaction-Enabled Semisynthesis of Taxanes Yields an Analogue with Reduced Chemotherapy-Induced Neuropathy. 多组分反应激活的紫杉烷半合成产生减少化疗诱导的神经病变的类似物。

IF 8.7

JACS Au Pub Date : 2025-08-25 eCollection Date: 2025-09-22 DOI: 10.1021/jacsau.5c00675

Xiang Fu, Haoyi Yang, Yaxin Li, Gejun Niu, Junxin Ren, Xiangrong Liu, Xinglin Li, Yukai Li, Jirong Shu, Weijie Guo, Tao Liu, Song Cai, Taoda Shi, Wenhao Hu

{"title":"Multicomponent Reaction-Enabled Semisynthesis of Taxanes Yields an Analogue with Reduced Chemotherapy-Induced Neuropathy.","authors":"Xiang Fu, Haoyi Yang, Yaxin Li, Gejun Niu, Junxin Ren, Xiangrong Liu, Xinglin Li, Yukai Li, Jirong Shu, Weijie Guo, Tao Liu, Song Cai, Taoda Shi, Wenhao Hu","doi":"10.1021/jacsau.5c00675","DOIUrl":"10.1021/jacsau.5c00675","url":null,"abstract":"Chemotherapy-induced peripheral neuropathy (TIPN) affects up to 97% of patients receiving taxane regimens, yet no single-agent solution exists. Current practice relies on coadministration of pain-modulating agents with taxanes, which adds complexity, potential drug-drug interactions, and patient-compliance hurdles. To address TIPN at its source, we set out to create a taxane analogue that intrinsically prevents neuropathy while retaining anticancer potency. Because building even small libraries of taxane derivatives via traditional semisynthetic or total-synthesis routes is laborious and step-intensive, we developed a late-stage, multicomponent reaction (MCR)-based platform on baccatin III for rapid, modular side-chain assembly. Using this approach, we synthesized over 30 C13-diversified taxanes in two steps with excellent stereocontrol and overall yields (35-68%). Lead compound 6v displays slightly better anticancer potency and a reduced TIPN effect than paclitaxel. This one-agent strategy streamlines therapy, obviates combination regimens, and establishes a broadly applicable MCR platform for natural-product optimization.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4299-4308"},"PeriodicalIF":8.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152434","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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