JACS Au最新文献

{"title":"Unambiguous Spectroscopic Characterization of a Gold Difluorocarbene.","authors":"Miquel Navarro, Louise Delaurenti, Alejandra Pita-Milleiro, Jesús Campos","doi":"10.1021/jacsau.5c00911","DOIUrl":"10.1021/jacsau.5c00911","url":null,"abstract":"<p><p>Gold-(I) carbenes, defined as [LAuCR₂]⁺, are key intermediates in catalysis. Their isolation is challenging due to the high electrophilic character of the carbene that cannot be tempered solely by π-backdonation from gold. Among those, the simple difluorocarbene complex has been invoked in several studies, but attempts to isolate it have failed, while its identification remains questionable. In this study, we report the unambiguous spectroscopic characterization of the gold difluorocarbene complex [P-AuCF₂]⁺, providing key insights into its structural and electronic features. The kinetic stabilization of the carbene was only possible owing to the shielding offered by a congested and cavity-shaped phosphine that prevents decomposition under strict anhydrous conditions. Besides, the nature of the anion is key to provide further thermal stability for prolonged times.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4604-4610"},"PeriodicalIF":8.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152533","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}

{"title":"Mismatch-Assisted Toehold Exchange Cascades for Magnetic Nanoparticle-based Nucleic Acid Diagnostics.","authors":"Rebecca Sack, Joshua Evans, Florian Wolgast, Meinhard Schilling, Thilo Viereck, Petr Šulc, Aidin Lak","doi":"10.1021/jacsau.5c00985","DOIUrl":"10.1021/jacsau.5c00985","url":null,"abstract":"<p><p>Sensitive, simple, and rapid detection of nucleic acid sequences at point-of-care settings is still an unmet quest. Magnetic readout assays combined with toehold-mediated strand displacement-based circuits are amplification- and wash-free, essential features for contributing to this demand. Nevertheless, nonenzymatic strand displacement circuits are slow, with low sensitivity for early disease diagnostics. Here, we propose novel mismatch-assisted toehold exchange (MATE) magnetic cascades, wherein magnetic susceptibility increases by dissociation of magnetic nanoparticles (MNPs) from engineered magnetic clusters upon detection of a nucleic acid target in solution. The MATE relies on the generation of an allosteric toehold by spontaneous dissociation to efficiently recycle the target, amplify magnetic signal output, and enhance the assay's kinetics. We show that introducing a mismatch in the allosteric toehold domain enhances the overall declustering kinetics 7-fold, as also confirmed with oxDNA simulations, with the largest effect gained for the mismatch being closest to where the branch migration by the target ends. By integrating MATE into magnetic diagnostics cascades, we demonstrate similar sensitivity in a 12-fold shorter assay time compared to our previous circuit design. Our work makes a major leap toward bringing MNP-based diagnostics much closer to the clinical point-of-care settings by offering a simple, rapid, isothermal, and nonenzymatic assay workflow.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4611-4624"},"PeriodicalIF":8.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152383","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}

{"title":"An Intelligent Allosteric DNAzyme Platform for On-Site Uracil-DNA Glycosylase Imaging and On-Demand Gene Regulation.","authors":"Yuqian Jiang, Yingying Chen, Xue Gong, Benrui Weng, Yuqiu He, Fuan Wang","doi":"10.1021/jacsau.5c00672","DOIUrl":"10.1021/jacsau.5c00672","url":null,"abstract":"<p><p>Uracil DNA glycosylase (UDG) is a crucial DNA repair enzyme involved in maintaining genomic stability. Precise monitoring of UDG facilitates in-depth elucidation of DNA repair and the onset and progression mechanisms of diseases. However, conventional UDG sensing approaches suffer from low accuracy and off-target signal leakage, limiting their applicability for precise <i>in situ</i> imaging and functional studies. Here, we report a UDG-activated allosteric DNAzyme (UAZ) platform that leverages an intramolecular recognition-allosteric-amplification strategy to achieve high-fidelity UDG detection and programmable gene regulation. In this design, the UDG-responsive uracil residue is introduced to disrupt the catalytic structure of DNAzyme and make DNAzyme inactive. Upon specific uracil excision by UDG, the precise allosteric reconfiguration restores the catalytic activity of DNAzyme, enabling efficient substrate cleavage and amplified fluorescence output. This mechanism eliminates off-target activation, realizing reliability and high-contrast UDG imaging. Furthermore, the modular UAZ platform was reprogrammed into a gene-silencing variant (gsUAZ) for selectively downregulating survivin mRNA in UDG-overexpressing cancer cells, thereby inducing cancer cell apoptosis with minimal effects on normal cells, ultimately realizing targeted gene therapy. This multifunctional UAZ system thus serves as both a sensitive molecular imaging tool and a targeted gene therapy agent, offering a versatile toolbox for disease diagnosis and precision gene therapy.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4288-4298"},"PeriodicalIF":8.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152397","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}

{"title":"Benzo-Extended [<i>n</i>]Phenacenes: e‑Flow Synthesis and Length-Dependent Properties.","authors":"Qiang Wang, Wei-Zhen Wang, Ruiying Zhang, Zi'ang Zhai, Xinyu Chen, Minggang Li, Yi Jin, Lingyun Zhu, Yuanming Li, Ke-Yin Ye","doi":"10.1021/jacsau.5c00653","DOIUrl":"10.1021/jacsau.5c00653","url":null,"abstract":"<p><p>This study presents an efficient method for synthesizing twisted benzo-extended [<i>n</i>]-phenacenes ([<i>n</i>]-BPs) featuring an electrochemical flow (e-flow) Scholl reaction of the corresponding [<i>n</i>]-BP precursors from a one-pot three-component Suzuki-Miyaura coupling reaction. The e-flow Scholl reaction offers advantages such as reduced oxidant usage and overoxidation byproducts, and easy scale-up through extended electrolysis time toward these intricate polycyclic aromatic hydrocarbons. In addition, the increase in molecular length decreases the optical bandgap of [<i>n</i>]-BPs and thus tunes their photophysical properties. This work provides a green and sustainable synthetic strategy for diverse [<i>n</i>]-BPs and enables facile bandgap modulation through π-conjugation extension, offering potential for organic semiconductor applications in optoelectronic devices.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4281-4287"},"PeriodicalIF":8.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152348","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}

{"title":"Electrochemical Investigation of Post-Translational Modification-Modulated Biomolecular Liquid-Liquid Phase Separation.","authors":"Yiwei Han, Jianyang Lu, Zhenzhen Guo, Peng Miao","doi":"10.1021/jacsau.5c00865","DOIUrl":"10.1021/jacsau.5c00865","url":null,"abstract":"<p><p>Post-translational modification (PTM) plays a key role in the regulation of liquid-liquid phase separation (LLPS), which participates in cell behaviors and pathological processes. Quantitative analysis of PTM-regulated LLPS is therefore essential for understanding cellular processes and discovering new disease targets. However, the membrane-free structure, dynamic characteristics, and distinct chemical microenvironment of biomolecular condensates pose challenges to traditional methods. In this contribution, an electrochemical method is proposed to analyze PTM-regulated LLPS for the first time by exploring its effect on electrochemical species. By taking dephosphorylation as a model, we demonstrate that the degree of LLPS initiated by dephosphorylation can be quantitatively assessed. Importantly, this label-free method does not require probe immobilization or signal tagging, making it easily extendable to various PTM-involved LLPS processes. Overall, this work provides a highly sensitive, simplified, and universal approach for the quantitative study of LLPS, with broad potential applications in physiological and pathological research studies.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4539-4546"},"PeriodicalIF":8.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152368","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}

{"title":"A Molecular Mechanism for the Reduction of the Cu Site in Lytic Polysaccharide Monooxygenases by Phenol Reductants.","authors":"Langxing Liao, Jian Kuang, Peng Wu, Xianhang Sang, Heng Yin, Changlin Tian, Xingwang Zhang, Wei Peng, Lu Yu, Binju Wang","doi":"10.1021/jacsau.5c00562","DOIUrl":"10.1021/jacsau.5c00562","url":null,"abstract":"<p><p>Lytic polysaccharide monooxygenases (LPMOs) play a pivotal role in the degradation of recalcitrant polysaccharides. As abundant reductants in nature, phenolic compounds may serve as sustainable reducing agents for LPMO reactions. However, the mechanism by which phenolic compounds drive the LPMO reactions remains elusive. In this study, we propose a molecular mechanism for the reduction of LPMO-Cu-(II) by phenolic reductants. Among the mechanisms that we investigated, the most favorable one involves the coordination replacement of water by the phenolic reductant. The coordination of phenols to LPMO-Cu-(II) significantly enhances the proton-coupled electron transfer process for the LPMO-Cu-(II) reduction. The proposed mechanism has been cross-validated by MD, QM/MM and QM/MM-MD studies, EPR spectroscopy, and phenol reductant oxidation experiments. Further analysis reveals that the different ligand effects between LPMOs and copper-dependent particulate methane monooxygenase (pMMO) can lead to divergent mechanisms for Cu-(II) reduction. These investigations underscore how differences in copper coordination environments dictate distinct reduction mechanisms. Collectively, our findings provide profound insights into phenol-mediated copper reduction in nature, advancing a broader understanding of copper enzyme reactivity and redox regulation.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4233-4248"},"PeriodicalIF":8.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152414","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}

{"title":"Sequential, Multiplexed Immunofluorescent Imaging of Live Cells Based on DNA-Mediated Reversible Fluorophore Attachment/Detachment with Antibodies.","authors":"Li Xu, Yuki Maeda, Noriko Nakamura, Seiichi Ohta","doi":"10.1021/jacsau.5c00752","DOIUrl":"10.1021/jacsau.5c00752","url":null,"abstract":"<p><p>Given the spectral overlap of fluorophores, traditional immunofluorescence imaging is limited by the number of proteins that can be imaged simultaneously. Although sequential imaging techniques have been proposed, in which repeated staining and destaining are performed to obtain the merged image of several proteins, they are applied only to fixed cells presumably due to their harsh conditions. Therefore, observation and analysis of live cells have not been achieved with the sequential imaging approach. In this study, we develop a sequential, multiplexed immunofluorescence imaging method for live cells using DNA as a detachable linker to bind antibodies to fluorophores. The use of toehold-mediated strand displacement of DNAs enables the attachment and detachment of fluorophores under mild physiological conditions. Consequently, at least six imaging cycles and the simultaneous use of three different fluorophores are demonstrated in live A431 and A549 cells, indicating the potential of imaging numerous protein markers in a single sample. Furthermore, by performing sequential staining at different time points, the dynamic expression changes of multiple proteins (EGFR, CD44, and Integrin β1) during EGF stimulation can also be detected. This approach is expected to facilitate comprehensive analysis of complex protein networks and their spatiotemporal regulation in live cells.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4389-4397"},"PeriodicalIF":8.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152407","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}

{"title":"A Metal-Peptide Framework as a Nanozyme for the Attenuation of Amyloid‑β Aggregation and Reactive Oxygen Species.","authors":"Zhuo Zhang, Mingchen Lv, Jiaxi Xu, Yaping Liu, Jinlong Qin, Zhen Fan, Jianzhong Du","doi":"10.1021/jacsau.5c00721","DOIUrl":"10.1021/jacsau.5c00721","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by abnormal performance in memory, cognition, and language, and it imposes a heavy economic burden worldwide. Amyloidosis and oxidative stress are highly associated with AD progression, yet limited clinical drugs are available at present. Nanozymes exhibit diverse enzyme-mimetic activities and have attracted widespread attention as a promising alternative candidate for scavenging reactive oxygen species to maintain the oxidation-antioxidation balance in cells. Neurotoxic amyloid-β (Aβ) aggregation is also a critical event in AD pathology. The development of dual-targeting nanomaterials with antiamyloidosis ability and enzyme-mimicking activity is expected to be a promising strategy for the treatment of amyloidosis and reactive oxygen species-mediated AD progression. Here, bimetallic-peptide framework nanozymes (CuZn-PEP NZs) with amyloid-β (Aβ) attenuating ability, multiple enzyme-mimicking properties, and broad-spectrum reactive oxygen species scavenging capacity were endowed to inhibit Aβ fibrillization, disaggregate Aβ fibrils, and scavenge Aβ fibril-induced reactive oxygen species. An obvious inhibitory effect on Aβ fibrillization and a disaggregation effect on Aβ fibrils were observed after treatment with CuZn-PEP NZs. Meanwhile, the cytotoxicity of Aβ fibrils toward PC12 cells was significantly reduced by CuZn-PEP NZs. Meanwhile, CuZn-PEP NZs with multiple redox pairs exhibit superoxide dismutase, catalase, and glutathione peroxidase-mimicking enzyme properties simultaneously, which further display cytoprotective effects against Aβ fibril-induced reactive oxygen species and mitochondrial damage. Besides, cellular studies verified that CuZn-PEP NZs possess excellent biocompatibility and blood-brain barrier penetration capacity. Overall, these bimetallic-peptide framework nanozymes represent a promising perspective for attenuation of amyloid-β aggregation and reactive oxygen species simultaneously, which highlights the potential of nanozymes for the treatment of amyloidosis and reactive oxygen species-mediated AD progression.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4346-4360"},"PeriodicalIF":8.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152426","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}

{"title":"Microneedle-Based DNA Tension Gauge Tethers Enable In Vivo Monitoring of Cell Mechanics during Skin Tissue Regeneration.","authors":"Xiaofei Ma, Yuanbin Guo, Haotian Li, Chen Zhao, Xuran Dai, Mo Ma, Pinyi Ma, Daqian Song, Yongxi Zhao, Feng Chen, Ying Sun","doi":"10.1021/jacsau.5c00870","DOIUrl":"10.1021/jacsau.5c00870","url":null,"abstract":"<p><p>The mechanical force exerted by dermal fibroblasts is crucial for promoting cutaneous tissue regeneration and wound healing. However, the implantation of a force interface in vivo or within tissue has become a new challenge in measuring mechanical force. Here, we report a microneedle patch with DNA tension gauge tethers (ME-TGT patch) to monitor the mechanical force of dermal fibroblasts in mice. Microneedles served as the force and electrode interface. When the integrin of the fibroblast membrane is successfully recognized by the integrin ligand (cRGDfk) in the tension probe, the duplex splits irreversibly by cellular mechanical force. The conformation rearrangement driven by a mechanical force can be converted into electrochemical signals. The ME-TGT patch can be used for verification of approximately 12 piconewtons (pN) of mechanical force exerted by fibroblasts in vitro and in vivo. Moreover, we used the ME-TGT patch to monitor cell mechanics during wound healing in skin tissue and found fluctuation (rising first and then falling in the process of 0-14 days) in mice. The ME-TGT patch allowed for monitoring mechanical force on fibroblasts in vivo and provided a novel tool for further research into mechanical mechanisms in tissue regeneration.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4560-4569"},"PeriodicalIF":8.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152344","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}

{"title":"Molecular Interactions within Nanoconfinement of Model DNA Nanostructures Controlled by Compensatory Kinetics as Revealed by Single-Molecule Fluorescence Analysis.","authors":"Nora Hagleitner-Ertuğrul, Yongzheng Xing, Juergen Pfeffermann, Alexia Rottensteiner, Anna Gaugutz, Denis G Knyazev, Peter Pohl, Stefan Howorka","doi":"10.1021/jacsau.5c00774","DOIUrl":"10.1021/jacsau.5c00774","url":null,"abstract":"<p><p>Molecular interactions under steric confinement are important in chemistry, biology, biotechnology, and medicine. The impact of nanoconfinement on the underpinning kinetics and affinities is, however, unclear. While theoretical frameworks predict any effect only for very fast diffusion-limited association kinetics, experimental studies report that molecules can be trapped inside confined spaces to increase the effective local concentration and impact binding kinetics. Understanding is furthermore complicated by poorly comparable confinement geometries and reactions. Here, we determine the kinetics and affinities for interactions slower than the diffusion limit using highly modular DNA origami nanopores as model nanoconfinement systems. The pores feature either inside or outside their narrow lumen a single receptor, which can bind to three differently sized biomolecular ligands. We conduct kinetic binding analysis at the single-molecule resolution using fluorescence correlation spectroscopy to readily acquire large datasets and help overcome limitations of other single-molecule approaches. Nanoconfinement is found to hinder ligand association and dissociation, even below the diffusion limit. Yet, both suppressed kinetics compensate for each other to yield the same overall equillibrium affinity as nonconfined receptors, while local concentration enhancement by ligand trapping was not observed. We expect our insights and experimental strategy to guide the development of biosensing nanopores and help advance the understanding of biological nanochannels.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4427-4438"},"PeriodicalIF":8.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152389","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}