JACS Au最新文献

{"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 (³IL) state localized on the thioester unit, as elucidated by computational analyses. However, their emission intensities and singlet oxygen (¹O₂)-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 ¹O₂-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 ¹O₂ 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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Advancing Multicolor Super-Resolution Volume Imaging: Illuminating Complex Cellular Dynamics","authors":"Navid Rabiee*,&nbsp; and ,&nbsp;Xun Lan*,&nbsp;","doi":"10.1021/jacsau.5c0031410.1021/jacsau.5c00314","DOIUrl":"https://doi.org/10.1021/jacsau.5c00314https://doi.org/10.1021/jacsau.5c00314","url":null,"abstract":"<p >The rapidly evolving field of live-cell super-resolution imaging has transformed our understanding of cellular structures and dynamic biological processes. This perspective delves into the importance and challenges of multicolor super-resolution volume imaging in the context of living cells, where the ability to visualize multiple molecular species simultaneously across three dimensions is critical for deciphering complex cellular functions. While recent innovations have made significant strides, challenges such as temporal and spatial resolution limits, photobleaching, and depth of field remain significant obstacles. This work explores emerging strategies aimed at overcoming these technical barriers, including the development of novel fluorophores, advanced computational techniques leveraging artificial intelligence, and hardware innovations in imaging systems. By addressing these challenges, the field is poised to move toward a future where high-precision, multicolor live-cell volume imaging becomes routine, enabling real-time visualization of intricate molecular interactions. The conclusion emphasizes that we are on the brink of a new frontier in cellular imaging, one that promises to revolutionize biological research and disease treatment by providing unprecedented access to the molecular mechanisms governing life at its most fundamental level.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2388–2419 2388–2419"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338025","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":"Effect of Sulfonation Level on the Percolated Morphology and Proton Conductivity of Hydrated Fluorine-Free Copolymers: Experiments and Simulations","authors":"Sol Mi Oh,&nbsp;Victoria S. Lee,&nbsp;William F. Drayer,&nbsp;Max S. Win,&nbsp;Lindsay F. Jones,&nbsp;Courtney M. Leo,&nbsp;Justin G. Kennemur,&nbsp;Amalie L. Frischknecht* and Karen I. Winey*,&nbsp;","doi":"10.1021/jacsau.5c0021810.1021/jacsau.5c00218","DOIUrl":"https://doi.org/10.1021/jacsau.5c00218https://doi.org/10.1021/jacsau.5c00218","url":null,"abstract":"<p >Using all-atom molecular dynamics simulations and a variety of experimental methods, we previously reported on a linear polyethylene with pendant phenyl sulfonated groups precisely on every fifth carbon along the backbone. With increasing relative humidity this fluorine-free polymer self-assembled to form nanoscale water channels and exhibited exceptional proton conductivity. Expanding upon those findings, here we explore partially sulfonated random copolymers, referred to as <i>p</i>5PhSH-<i>Y</i>. Using either acetyl sulfate or sulfuric acid, a wide range of sulfonation levels were prepared (<i>Y</i> = 34–98%) corresponding to ion-exchange capacities (IEC) of 2.0–4.4 mmol/g. Combining experimental techniques and all-atom molecular dynamics simulations, we study the effect of <i>Y</i> on water uptake, nanoscale morphology, and the proton/water transport properties of <i>p</i>5PhSH-<i>Y</i>. The proton conductivity of <i>p</i>5PhSH-<i>Y</i> increases with relative humidity and with <i>Y</i> and achieves values in excess of 0.1 S/cm. These high conductivities are attributed to high IEC and well-developed nanoscale percolated hydrophilic domains made possible by the flexible backbone. We quantitatively describe the nature of the water channels using the characteristic distance, channel width distribution, the area per sulfonate group at the hydrophilic/hydrophobic interface, and the fractal dimension. Notably, the channel widths and the areas per sulfonate group are nominally independent of the level of sulfonation, while depending significantly on the level of hydration. The fractal dimension of the water channels correlates strongly with the water diffusion coefficients calculated from the molecular dynamics (MD) simulations. These findings demonstrate that the <i>p</i>5PhSH-<i>Y</i> hydrocarbon copolymers can be modified to tune properties, particularly proton conductivity.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2641–2653 2641–2653"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337948","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":"Inverse Design of Block Polymer Materials with Desired Nanoscale Structure and Macroscale Properties","authors":"Vinson Liao,&nbsp; and ,&nbsp;Arthi Jayaraman*,&nbsp;","doi":"10.1021/jacsau.5c0037710.1021/jacsau.5c00377","DOIUrl":"https://doi.org/10.1021/jacsau.5c00377https://doi.org/10.1021/jacsau.5c00377","url":null,"abstract":"<p >The rational design of novel polymers with tailored material properties has been a long-standing challenge in the field due to the large number of possible polymer design variables. To accelerate this design process, there is a critical need to develop novel tools to aid in the inverse design process and to efficiently explore the high-dimensional polymer design space. Optimizing macroscale material properties for polymeric systems is even more challenging than inorganics and small molecules as these properties are dictated by features on a multitude of length scales, ranging from the chosen monomer chemistries to the chain level design to larger-scale (nm to microns) domain structures. In this work, we present an efficient high-throughput in-silico based framework to effectively design high-performance polymers (blends, copolymers) with desired multiscale nanostructure and macroscale properties which we call RAPSIDY 2.0 - Rapid Analysis of Polymer Structure and Inverse Design strategY 2.0. This new version of RAPSIDY builds upon our previous work, RAPSIDY 1.0, which focused purely on identifying polymer designs that stabilized a desired nanoscale morphology. In RAPSIDY 2.0 we use a combination of molecular dynamics (MD) simulations and Bayesian optimization driven active learning to optimally query high-dimensional polymer design spaces and propose promising design candidates that simultaneously stabilize a selected nanoscale morphology and exhibit desired macroscale material properties (e.g., tensile strength, thermal conductivity). We utilize MD simulations with polymer chains preplaced into selected nanoscale morphologies and perform virtual experiments to determine the stability of the chosen polymer design within the target morphology and calculate the desired macroscale material properties. Our methodology directly addresses the unique challenge associated with copolymers whose macroscale properties are a function of both their chain design and mesoscale morphology, which are coupled. We showcase the efficacy of our methodology in engineering high-performance blends of block copolymers that exhibit (1) high thermal conductivity and (2) high tensile strength. We also discuss the impact of our work in accelerating the design of novel polymeric materials for targeted applications.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2810–2824 2810–2824"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338099","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":"Triplet Vinylidenes Based on (Benz)imidazole and 1,2,3-Triazole N-Heterocycles","authors":"Yury Kutin,&nbsp;Justus Reitz,&nbsp;Maria Drosou,&nbsp;Patrick W. Antoni,&nbsp;Yijie He,&nbsp;Victor R. Selve,&nbsp;Sergius Boschmann,&nbsp;Anton Savitsky,&nbsp;Dimitrios A. Pantazis*,&nbsp;Müge Kasanmascheff* and Max M. Hansmann*,&nbsp;","doi":"10.1021/jacsau.5c0049110.1021/jacsau.5c00491","DOIUrl":"https://doi.org/10.1021/jacsau.5c00491https://doi.org/10.1021/jacsau.5c00491","url":null,"abstract":"<p >Triplet vinylidenes, a new class of carbon-centered diradicals containing a monosubstituted carbon atom<u>,</u> remain largely unexplored. A series of triplet vinylidenes based on five-membered heterocycles, featuring 2- and 4-imidazole, benzimidazole as well as 1,2,3-triazole backbones, are generated upon irradiation of stable diazoalkenes and are investigated by electron paramagnetic resonance (EPR) spectroscopy. While the calculated S/T gaps strongly vary (∼9.9–18.4 kcal/mol), the experimental zero-field splitting (ZFS) <i>D</i> values are positioned in a rather narrow and characteristic range of <i>D</i> ∼ 0.366–0.399 cm^–1. Electron nuclear double resonance (ENDOR) studies with ¹³C-labeled samples combined with quantum chemical calculations reveal a common motif of <i>A</i>_iso(¹³C) ≈ 50 MHz for the electronic structure of the vinylidene class. EPR decay experiments confirm that steric and electronic tuning of the heterocycle can hinder C–H activation pathways leading to the highest reported stabilities of up to 150 K. Quantum chemical studies elucidate and contrast plausible C–H insertion pathways, identifying an early triplet-to-singlet spin surface transition as the key factor that governs the stability of the vinylidenes.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2884–2897 2884–2897"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00491","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338019","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}