JACS AuPub Date : 2025-06-09eCollection Date: 2025-06-23DOI: 10.1021/jacsau.5c00314
Navid Rabiee, Xun Lan
{"title":"Advancing Multicolor Super-Resolution Volume Imaging: Illuminating Complex Cellular Dynamics.","authors":"Navid Rabiee, Xun Lan","doi":"10.1021/jacsau.5c00314","DOIUrl":"10.1021/jacsau.5c00314","url":null,"abstract":"<p><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"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510106","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}
JACS AuPub Date : 2025-06-09DOI: 10.1021/jacsau.5c0031410.1021/jacsau.5c00314
Navid Rabiee*, and , Xun Lan*,
{"title":"Advancing Multicolor Super-Resolution Volume Imaging: Illuminating Complex Cellular Dynamics","authors":"Navid Rabiee*, and , Xun Lan*, ","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}
JACS AuPub Date : 2025-06-09eCollection Date: 2025-06-23DOI: 10.1021/jacsau.5c00379
Yusheng Liao, Yifan Sun, Hui Yu, Jiali Ren, Fengjiao He
{"title":"High-Fidelity, One-Pot Nucleic Acid Amplification via OMEGA IsrB Nickase Cycling for Clinical Pathogen Detection.","authors":"Yusheng Liao, Yifan Sun, Hui Yu, Jiali Ren, Fengjiao He","doi":"10.1021/jacsau.5c00379","DOIUrl":"10.1021/jacsau.5c00379","url":null,"abstract":"<p><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 Pseudomonas aeruginosa 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"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510133","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, Natsumi Maeda, Daisuke Yokogawa, Akira Matsumoto, Keiji Maruoka","doi":"10.1021/jacsau.5c00400","DOIUrl":"10.1021/jacsau.5c00400","url":null,"abstract":"<p><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"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510094","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}
JACS AuPub Date : 2025-06-09eCollection Date: 2025-06-23DOI: 10.1021/jacsau.5c00357
Lars E Burmeister, Lucie J Groth, Philipp R Meinhold, Johannes P Zurwellen, Dirk Bockfeld, René Frank, Michael Karnahl, Matthias Tamm, Stefanie Tschierlei
{"title":"Photoactive Neutral Three-Coordinate Cu(I) Complexes of Anionic N‑Heterocyclic Carbenes.","authors":"Lars E Burmeister, Lucie J Groth, Philipp R Meinhold, Johannes P Zurwellen, Dirk Bockfeld, René Frank, Michael Karnahl, Matthias Tamm, Stefanie Tschierlei","doi":"10.1021/jacsau.5c00357","DOIUrl":"10.1021/jacsau.5c00357","url":null,"abstract":"<p><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"},"PeriodicalIF":8.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510095","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}
JACS AuPub Date : 2025-06-05eCollection Date: 2025-06-23DOI: 10.1021/jacsau.5c00377
Vinson Liao, Arthi Jayaraman
{"title":"Inverse Design of Block Polymer Materials with Desired Nanoscale Structure and Macroscale Properties.","authors":"Vinson Liao, Arthi Jayaraman","doi":"10.1021/jacsau.5c00377","DOIUrl":"10.1021/jacsau.5c00377","url":null,"abstract":"<p><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"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510137","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}
JACS AuPub Date : 2025-06-05eCollection Date: 2025-06-23DOI: 10.1021/jacsau.5c00085
Katherine A Gosselé, Irene Latino, Eleen Laul, Mariia S Kirillova, Vlad Pascanu, Emanuele Carloni, Rajiv K Bedi, Chiara Pizzichetti, Amedeo Caflisch, Santiago F González, Cristina Nevado
{"title":"Selective CBP/EP300 Bromodomain Inhibitors: Novel Epigenetic Tools to Counter TNF-α-Driven Inflammation.","authors":"Katherine A Gosselé, Irene Latino, Eleen Laul, Mariia S Kirillova, Vlad Pascanu, Emanuele Carloni, Rajiv K Bedi, Chiara Pizzichetti, Amedeo Caflisch, Santiago F González, Cristina Nevado","doi":"10.1021/jacsau.5c00085","DOIUrl":"10.1021/jacsau.5c00085","url":null,"abstract":"<p><p>Tumor necrosis factor α (TNF-α) is a central driver of inflammation in autoimmune conditions such as Crohn's disease and rheumatoid arthritis (RA). Targeting epigenetic regulators involved in cytokine expression holds therapeutic promise, yet the precise role of the CBP/EP300 bromodomains (BRDs) in modulating immune responses remains poorly understood. Here, we introduce a distinct class of selective CBP/EP300-BRD inhibitors based on a unique 3-methylcinnoline acetyl-lysine mimic, identified through high-throughput fragment docking. These inhibitors significantly reduce TNF-α-driven cytokine expression <i>in vitro</i> by blocking NFκB signaling in immune cells. <i>In vivo</i>, BRD inhibition led to a robust anti-inflammatory effect, decreasing cytokine secretion (including IL-1β, MCP-1, IL-1α, and IL-6) and preventing immune cell migration to inflamed lymph nodes in a TNF-α-stimulated murine model. Our findings highlight CBP/EP300-BRDs as promising targets for autoimmune therapy, with these non-cytotoxic inhibitors offering a potential complementary approach for RA and other TNF-α-mediated inflammatory conditions.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2491-2499"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510098","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}
JACS AuPub Date : 2025-06-05eCollection Date: 2025-06-23DOI: 10.1021/jacsau.5c00218
Sol Mi Oh, Victoria S Lee, William F Drayer, Max S Win, Lindsay F Jones, Courtney M Leo, Justin G Kennemur, Amalie L Frischknecht, Karen I Winey
{"title":"Effect of Sulfonation Level on the Percolated Morphology and Proton Conductivity of Hydrated Fluorine-Free Copolymers: Experiments and Simulations.","authors":"Sol Mi Oh, Victoria S Lee, William F Drayer, Max S Win, Lindsay F Jones, Courtney M Leo, Justin G Kennemur, Amalie L Frischknecht, Karen I Winey","doi":"10.1021/jacsau.5c00218","DOIUrl":"10.1021/jacsau.5c00218","url":null,"abstract":"<p><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"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510127","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}
JACS AuPub Date : 2025-06-05eCollection Date: 2025-06-23DOI: 10.1021/jacsau.5c00491
Yury Kutin, Justus Reitz, Maria Drosou, Patrick W Antoni, Yijie He, Victor R Selve, Sergius Boschmann, Anton Savitsky, Dimitrios A Pantazis, Müge Kasanmascheff, Max M Hansmann
{"title":"Triplet Vinylidenes Based on (Benz)imidazole and 1,2,3-Triazole N‑Heterocycles.","authors":"Yury Kutin, Justus Reitz, Maria Drosou, Patrick W Antoni, Yijie He, Victor R Selve, Sergius Boschmann, Anton Savitsky, Dimitrios A Pantazis, Müge Kasanmascheff, Max M Hansmann","doi":"10.1021/jacsau.5c00491","DOIUrl":"10.1021/jacsau.5c00491","url":null,"abstract":"<p><p>Triplet vinylidenes, a new class of carbon-centered diradicals containing a monosubstituted carbon atom, 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<sup>-1</sup>. Electron nuclear double resonance (ENDOR) studies with <sup>13</sup>C-labeled samples combined with quantum chemical calculations reveal a common motif of <i>A</i> <sub>iso</sub>(<sup>13</sup>C) ≈ 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"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510101","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}
JACS AuPub Date : 2025-06-05DOI: 10.1021/jacsau.5c0021810.1021/jacsau.5c00218
Sol Mi Oh, Victoria S. Lee, William F. Drayer, Max S. Win, Lindsay F. Jones, Courtney M. Leo, Justin G. Kennemur, Amalie L. Frischknecht* and Karen I. Winey*,
{"title":"Effect of Sulfonation Level on the Percolated Morphology and Proton Conductivity of Hydrated Fluorine-Free Copolymers: Experiments and Simulations","authors":"Sol Mi Oh, Victoria S. Lee, William F. Drayer, Max S. Win, Lindsay F. Jones, Courtney M. Leo, Justin G. Kennemur, Amalie L. Frischknecht* and Karen I. Winey*, ","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}