JACS Au最新文献

{"title":"Biomineralization-Driven Advances in Materials Science and Biomedical Engineering.","authors":"Jun Guo, Feng Gao, Feng Zhang, Xinmin Zhao, Ruoyang Zhao","doi":"10.1021/jacsau.5c00669","DOIUrl":"10.1021/jacsau.5c00669","url":null,"abstract":"<p><p>This perspective articulates the transformative role of biomineralization in materials science and biomedical engineering. Establishing fundamental principles through systematic analysis of mineralization categories, dynamic processes, and crystal nucleation/growth mechanisms, the review progresses to contemporary bioinspired applicationsfrom biotemplated nanocarriers for targeted drug delivery to precision tooth remineralization and engineered bone scaffolds. Critical examination of persistent challenges (morphological precision, scalable production, biological template design) precedes discussion of emerging technological vectors: superhydrophilic/hydrophobic interfacial engineering and hybrid composite systems. The discourse extends to diagnostic biosensing platforms and AI-optimized mineralization architectures as frontier applications. Conclusively, the work frames an interdisciplinary convergence of biological, chemical, and engineering paradigms essential for realizing biomineralization's potential while mapping strategic research directions.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4134-4154"},"PeriodicalIF":8.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152428","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":"Arrested Cooperative Electron Transfer by Stabilization of a Long-Lived Confined Unpaired Electron.","authors":"Cheriehan Hessin, Mokhtar Ben Ghanem, Nolwenn Le Breton, Sylvie Choua, Aurélien Moncomble, Laurence Grimaud, Hervé Vezin, Marine Desage-El Murr","doi":"10.1021/jacsau.5c00484","DOIUrl":"10.1021/jacsau.5c00484","url":null,"abstract":"<p><p>Cooperative multielectron transfer is central to electron storage strategies and small-molecule activation and involves a thermodynamically favored second electron transfer occurring after the first electron transfer. This is the trademark of molecular systems with inverted redox potentials, but it is counterintuitive from an energetic point of view, and the nature of the transient intermediates involved has remained elusive. Using a nickel complex with inverted redox potentials, we show that a weakly coordinating anion (WCA), such as BAr^F ₄ ^- ([B-(C₆H₃(CF₃)₂)₄]^-), can act as a kinetic trap for the second electron to be transferred. Combined electrochemistry, UV-visible spectroscopy, advanced EPR studies, and theoretical calculations support its existence as a stabilized, confined unpaired electron, close to the concept of a solvated electron. This work sheds light on the nature of energized intermediates in cooperative electron transfer and the possibility of influencing that process through counterion effects.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4204-4210"},"PeriodicalIF":8.7,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152399","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":"Late-Stage Functionalization of Lysine to Organelle-Targeting Fluorescent Probes.","authors":"Patricia Rodriguez, Ankita Misra, Monika Raj","doi":"10.1021/jacsau.5c00680","DOIUrl":"10.1021/jacsau.5c00680","url":null,"abstract":"<p><p>The late-stage functionalization of peptides presents a promising avenue for expanding their chemical diversity and properties, particularly in the realm of drug discovery. Herein, we present a powerful late-stage functionalization (LSF) strategy for peptides that includes an addition-cyclization-aromatization (ACA) transformation to generate 2,3,4,6-substituted pyridinium, with inherent fluorescence, specifically at lysine residues. This method enables the precise and irreversible labeling of diverse peptide sequences, both in solution and on solid support, with quantum yields ranging from 0.02 to 0.03. Importantly, the 2,3,4,6-substituted pyridinium core represents a delocalized lipophilic cation (DLC), exhibiting strong mitochondrial-targeting properties. This unique platform facilitates real-time imaging and targeted delivery of drugs and peptides to mitochondria without the need for additional tagging, offering significant potential for theranostic applications.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4309-4320"},"PeriodicalIF":8.7,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208662","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":"Lipid-Oxidative Enzymes and Fenton-Like Reactions Are Synergistic in Promoting Membrane Lipid Peroxidation.","authors":"Hye Jin Jeong, Sein Min, Lucas A Villalon, Keunhong Jeong, Jean K Chung","doi":"10.1021/jacsau.5c00696","DOIUrl":"10.1021/jacsau.5c00696","url":null,"abstract":"<p><p>Lipid peroxidation (LPO) of cellular membranes is a near-universal indicator of aging and disease, yet the mechanistic link between the LPO and disease remains elusive. In this study, we demonstrate that efficient LPO in model membranes is accomplished through synergy between selective enzymatic oxidation by lipoxygenase (LOX) and nonspecific oxidation by reactive oxygen species (ROS). Through fluorescence-based oxidation kinetic measurements, we show that soluble ROS alone fails to induce significant oxidation under physiologically relevant conditions. However, enzymatic oxidation enhances the ROS-driven LPO by altering membrane permeability. Strikingly, this process drives the macroscopic clustering of the membrane-bound protein KRAS on giant unilamellar vesicles (GUVs), revealing potential functional consequences. If this mechanism extends to living cells, it could reshape our understanding of oxidative stress in disease. Our findings represent an essential step toward advancing an integrated understanding of oxidative membrane biology, encompassing both enzymatic oxidation and oxidation by ROS.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 9","pages":"4337-4345"},"PeriodicalIF":8.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152392","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":"Lanthanide Ionic Radius Modulation for Tailored Triple-Cross-Linked Luminescent Gelatin/Alginate Hydrogels: Structural, Mechanical, and Sensing Insights","authors":"Shu-Ying Wu,&nbsp;Yu-Ning An and Yi-Cheun Yeh*,&nbsp;","doi":"10.1021/jacsau.5c00647","DOIUrl":"https://doi.org/10.1021/jacsau.5c00647","url":null,"abstract":"<p >Lanthanide-containing hydrogels have emerged as a promising category of luminescent materials for sensing applications. However, a systematic investigation of lanthanide ions with varying ionic radii to reveal the structure–property–function relationships within the hydrogel network remains unexplored. This study integrates different lanthanide (Ln³⁺) ions (i.e., samarium (Sm³⁺), europium (Eu³⁺), or terbium (Tb³⁺)) into polymeric networks composed of phenylboronic acid-grafted polyethylenimine (PBA-PEI)-modified gelatin (PPG) and alginate-dialdehyde (ADA), resulting in triple-cross-linked PPG/ADA-Ln³⁺ hydrogels that are stabilized via dynamic bonds. The influence of lanthanide ionic radius on the microstructures, properties (i.e., luminescence, rheological behavior, mechanical strength, swelling capacity, and stability), and sensing performance is systematically investigated. PPG/ADA-Ln³⁺ lyophilized hydrogels demonstrate a remarkable ability to differentiate acidic and basic vapors in volatile organic compounds through linear discriminant analysis (LDA), and this capability is further explored for bacterial differentiation. Overall, smaller Tb³⁺ ions induce the formation of denser networks with enhanced mechanical properties and contribute superior sensing capabilities to the hydrogel, attributed to optimized coordination with the carboxylate groups of the polymers. This comprehensive study elucidates the critical role of lanthanide ionic radius in shaping the structural and functional attributes of PPG/ADA-Ln³⁺ hydrogels, showing their potential as versatile biomaterials with tailored properties for a wide range of applications.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 8","pages":"4022–4035"},"PeriodicalIF":8.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jacsau.5c00647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892602","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":"Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies","authors":"Kazuma Murakami*,&nbsp;Thi Hong Van Nguyen,&nbsp;Chioko Nagao,&nbsp;Kenji Mizuguchi and Gal Bitan*,&nbsp;","doi":"10.1021/jacsau.5c00269","DOIUrl":"https://doi.org/10.1021/jacsau.5c00269","url":null,"abstract":"<p >Inhibition of amyloidogenic-protein oligomerization and aggregation is a promising therapy-development strategy for proteinopathies, such as Alzheimer’s and Parkinson’s diseases, in which proteins self-associate into a variety of abnormal, toxic assemblies. Despite discovery of numerous compounds modulating the self-assembly process in vitro, few have reached advanced clinical trials, and none have translated into effective therapy to date. A potential reason is a lack of clear mechanistic understanding of the interaction between the inhibitors/modulators and the target metastable protein assemblies. A unique class of compounds targets specifically Lys residues, which have been shown to be important mediators of many amyloidogenic-protein aberrant self-assembly processes due to their participation in both electrostatic and hydrophobic interactions. Although seemingly paradoxical, as these compounds do not target a specific protein, compounds targeting Lys show a remarkable ability to selectively disrupt the interactions mediating abnormal protein self-assembly. Such compounds include covalent and noncovalent Lys-binding small molecules, as well as agents controlling Lys-post-translational modification (PTM). Recent advances in this area show that the application of Lys-targeting inhibitors in antiamyloid drug discovery campaigns and Lys-reactive rational-design approaches have led to intriguing results in multiple systems, including animal models of various proteinopathies. As this strategy is applicable and promising for targeting most of the proteins involved in proteinopathies, including amyloid β-protein, tau, and α-synuclein, here we highlight Lys-binding inhibitors of abnormal protein self-assembly leading to preclinical therapeutic applications for the central nervous system.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 8","pages":"3680–3700"},"PeriodicalIF":8.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jacsau.5c00269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892558","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":"Enhancing Reaction Compatibility in Telescoped Multistep Flow Synthesis via Hybridizing Micro Packed-Bed/Micro Tubing Reactors: Application to Cyproflanilide and Broflanilide","authors":"Xingyu Zhang,&nbsp;Gangqin Huang,&nbsp;Yihui Ou,&nbsp;Zeyi Luo,&nbsp;Zheyao Huang,&nbsp;Chenguang Liu* and Fen-Er Chen*,&nbsp;","doi":"10.1021/jacsau.5c00771","DOIUrl":"https://doi.org/10.1021/jacsau.5c00771","url":null,"abstract":"<p >Telescoped multistep flow synthesis, which integrates sequential reactions into a seamless sequence without intermediate isolation, serves as a transformative force propelling the advancement of continuous drug manufacturing. However, interstep incompatibility caused by varying reaction conditions hinders its development and application. To address this critical challenge, we present a hybrid flow system combining micro packed bed reactors (μPBRs) and microtubular reactors (μTRs). μPBRs house heterogeneous catalytic processes, improving solvent and reagent compatibility and operational ease, while μTRs enable intensified homogeneous reactions with enhanced kinetics. This hybrid strategy was applied to the telescoped synthesis of <i>N</i>-acyl-<i>N</i>-alkyl anilines─key pharmacophores in pharmaceuticals and agrichemicals─via a four-step continuous process: nitro reduction, reductive amination, amide coupling, and ester hydrolysis. High yields of <i>N</i>-acyl-<i>N</i>-alkyl anilines <b>5a</b> (87% in 15.5 min) and <b>5b</b> (84% in 13.8 min) were achieved without intermediate isolation. Furthermore, the complete eight-step continuous synthesis of both insecticides, cyproflanilide and broflanilide, was also realized. Notably, this project leveraged dibenzo-18-crown-6 to modulate intrinsic kinetics and tailored flow configurations to intensify apparent kinetics, thus enabling a scalable, biphasic (water/oil) sulfinato-dehalogenation protocol, producing insecticide intermediates at the kilogram-per-day scale. This hybrid strategy demonstrates versatility in addressing reaction incompatibility during telescoped flow synthesis, advancing the practical implementation of continuous manufacturing.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 8","pages":"4114–4122"},"PeriodicalIF":8.7,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jacsau.5c00771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892722","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":"Design and Synthesis of 3-Amino-4-azidoethoxyfurazan: A Supramolecular Energetic Material with Insensitivity Properties","authors":"Yang Wu,&nbsp;Yuezhou Liu,&nbsp;Ke Liang,&nbsp;Xiaokai He,&nbsp;Yingzhe Liu,&nbsp;Chuan Xiao and Yinglei Wang*,&nbsp;","doi":"10.1021/jacsau.5c00511","DOIUrl":"https://doi.org/10.1021/jacsau.5c00511","url":null,"abstract":"<p >High-performance insensitive energetic materials have long been a central focus of energetic materials research. To effectively balance high energy density and insensitivity, a structure-based screening was performed using the Cambridge Crystallographic Data Centre database. Consequently, a strategy enhancing the stability of energetic compounds through supramolecular assembly based on self-complementary hydrogen bonding was developed. Guided by this approach, a novel energetic compound, 3-amino-4-azidoethoxyfurazan (AAeF), was designed and synthesized successfully. Single-crystal X-ray diffraction analysis revealed the formation of two pairs of self-complementary hydrogen bonds within AAeF, which adopt a zigzag arrangement, resulting in a supramolecular structure characterized by rigid “plate-like” and flexible “chain-like” configurations. This structure, containing the “Fz–NH₂–N₃” moiety, efficiently absorbs external impacts and enhances the stability of energetic groups via hydrogen bond-mediated electron transfer, resulting in exceptional insensitivity characteristics for AAeF (IS &gt; 90 J). These results highlight that supramolecular assembly driven by self-complementary hydrogen bonding is an effective strategy for improving the safety of energetic materials, particularly for applications in high-safety melt-cast explosives.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 8","pages":"3904–3913"},"PeriodicalIF":8.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jacsau.5c00511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892613","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":"Bridged Azobenzene Exhibits Fully Reversible Photocontrolled Binding to a G-Quadruplex DNA/Duplex Junction","authors":"Javier Ramos-Soriano*,&nbsp;Y. Jennifer Jiang,&nbsp;Bowen Deng,&nbsp;Michael P. O′Hagan,&nbsp;Aditya G. Rao,&nbsp;Doudou Lu,&nbsp;Susanta Haldar,&nbsp;A. Sofia F. Oliveira,&nbsp;Adrian J. Mulholland* and M. Carmen Galan*,&nbsp;","doi":"10.1021/jacsau.5c00532","DOIUrl":"https://doi.org/10.1021/jacsau.5c00532","url":null,"abstract":"<p >The ability to selectively control DNA conformation using light as an external stimulus offers unique opportunities to control specific DNA sequences in biological settings and to develop nucleotide-based nanodevices. We describe a duplex/G-quadruplex (G4) junction-binding chemotype derived from a cyclic azobenzene core that reversibly photoswitches between <i>cis</i> and <i>trans</i> isomers, mediated exclusively by visible light under physiological conditions. We demonstrate the selective binding of the elongated <i>trans</i> conformation, with over 50-fold higher affinity, toward LTR-III G4 (an important HIV-1 sequence), and show that binding and dissociation from the LTR-III G4 can be controlled reversibly by alternate irradiation with low-intensity blue and green light. NMR and MD simulations indicate that the different isomers exhibit very distinct binding modes. While the elongated <i>trans</i> ligand preferentially binds at the G4/duplex junction of the LTR-III sequence, a DNA motif which is gaining increasing attention as a potential drug target, the bent <i>cis</i> isomer favors the duplex region.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 8","pages":"3846–3857"},"PeriodicalIF":8.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jacsau.5c00532","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892651","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":"Quantifying Landscape and Flux from Single-Cell Omics: Unraveling the Physical Mechanisms of Cell Function","authors":"Ligang Zhu,&nbsp; and ,&nbsp;Jin Wang*,&nbsp;","doi":"10.1021/jacsau.5c00620","DOIUrl":"https://doi.org/10.1021/jacsau.5c00620","url":null,"abstract":"<p >Recent advancements in single-cell sequencing technology have reshaped our understanding of cellular processes. While in the realm of biological research, the understanding of the underlying physical and chemical mechanisms from single-cell omics stands as a promising frontier, yet it is still not quite adequately explored. This knowledge gap stems from the complexities of mapping nonequilibrium physical and chemical principles onto the heterogeneous and complex dynamics of cellular functions. Herein, several key biological processes are highlighted to embark on this challenging journey of harnessing the power of single-cell omics to elucidate the nonequilibrium physical and chemical basis of various biological cell functions, including cell cycle, cell differentiation/reprogramming, cancer progression and metastasis, and embryonic dynamic development. This perspective presents breakthrough insights into cell division and differentiation, highlighting the nonequilibrium landscape and flux as the driving forces governing the cellular function which can be quantified through the single-cell omics data, providing new insights into cellular plasticity and fate determination. In addition, it provides possible early warning signals of cancer formation and metastasis based on omics data. Venturing into the wonders of dynamical development, it shows the uncovered nonequilibrium physicochemical mechanisms determined by the dynamical landscape-flux of embryogenesis from time-resolved single-cell data. This perspective further offers an outlook on challenges and opportunities for the integrations of spatiotemporal multiomics and nonequilibrium physical and chemical theories, in anticipation of a more comprehensive and in-depth understanding of the myriad processes of life. Hence, this perspective summarizes key advances in this emerging field and points to the next opportunities and challenges to fully integrate the potential of single-cell biotechnology and physical chemistry theory in life science.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 8","pages":"3738–3757"},"PeriodicalIF":8.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/jacsau.5c00620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892616","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}