JACS Au最新文献

{"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}

{"title":"An Integrative Framework for Mapping Orientational Landscapes of Peripheral Membrane Proteins by Paramagnetic NMR and Atomistic Simulation","authors":"Dan Liu,&nbsp;Yu Ni,&nbsp;Leilei Shui and Dong Long*,&nbsp;","doi":"10.1021/jacsau.5c0033110.1021/jacsau.5c00331","DOIUrl":"https://doi.org/10.1021/jacsau.5c00331https://doi.org/10.1021/jacsau.5c00331","url":null,"abstract":"<p >The functions of peripheral membrane proteins (PMPs) can be critically influenced by their orientations on membrane surfaces, which are inherently dynamic and challenging to characterize with precision. Molecular dynamics (MD) simulations, while powerful, face limitations in force field accuracy and sampling, particularly for systems involving intricate protein–lipid interactions. Here, we employ artifact-free membrane paramagnetic relaxation enhancement (mPRE) data as a quantitative benchmark to evaluate and refine MD simulations of KRas4B, a classical PMP, bound to anionic bilayers. Discrepancies between state-of-the-art simulations and experimental data are quantified and attributed to both inadequate sampling and force field inaccuracies. By fine-tuning the electrostatic interactions between the negatively charged protein and lipid, moderate improvement in agreement with experimental data was achieved. Furthermore, we employed the maximum entropy method (MEM) to reconcile MD simulations with the mPRE rates, generating a statistically robust orientational ensemble that quantitatively reproduces the mPRE measurements. This integrative approach establishes a powerful framework for atomic-detail characterization of orientational landscapes of PMPs, offering insights into their functional regulation and guiding therapeutic strategies.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2728–2737 2728–2737"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338098","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":"Selective CBP/EP300 Bromodomain Inhibitors: Novel Epigenetic Tools to Counter TNF-α-Driven Inflammation","authors":"Katherine A. Gosselé,&nbsp;Irene Latino,&nbsp;Eleen Laul,&nbsp;Mariia S. Kirillova,&nbsp;Vlad Pascanu,&nbsp;Emanuele Carloni,&nbsp;Rajiv K. Bedi,&nbsp;Chiara Pizzichetti,&nbsp;Amedeo Caflisch*,&nbsp;Santiago F. González* and Cristina Nevado*,&nbsp;","doi":"10.1021/jacsau.5c0008510.1021/jacsau.5c00085","DOIUrl":"https://doi.org/10.1021/jacsau.5c00085https://doi.org/10.1021/jacsau.5c00085","url":null,"abstract":"<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 2491–2499"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337946","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 Integrative Framework for Mapping Orientational Landscapes of Peripheral Membrane Proteins by Paramagnetic NMR and Atomistic Simulation.","authors":"Dan Liu, Yu Ni, Leilei Shui, Dong Long","doi":"10.1021/jacsau.5c00331","DOIUrl":"10.1021/jacsau.5c00331","url":null,"abstract":"<p><p>The functions of peripheral membrane proteins (PMPs) can be critically influenced by their orientations on membrane surfaces, which are inherently dynamic and challenging to characterize with precision. Molecular dynamics (MD) simulations, while powerful, face limitations in force field accuracy and sampling, particularly for systems involving intricate protein-lipid interactions. Here, we employ artifact-free membrane paramagnetic relaxation enhancement (mPRE) data as a quantitative benchmark to evaluate and refine MD simulations of KRas4B, a classical PMP, bound to anionic bilayers. Discrepancies between state-of-the-art simulations and experimental data are quantified and attributed to both inadequate sampling and force field inaccuracies. By fine-tuning the electrostatic interactions between the negatively charged protein and lipid, moderate improvement in agreement with experimental data was achieved. Furthermore, we employed the maximum entropy method (MEM) to reconcile MD simulations with the mPRE rates, generating a statistically robust orientational ensemble that quantitatively reproduces the mPRE measurements. This integrative approach establishes a powerful framework for atomic-detail characterization of orientational landscapes of PMPs, offering insights into their functional regulation and guiding therapeutic strategies.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2728-2737"},"PeriodicalIF":8.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510107","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":"Identifying Key Factors Influencing Advanced Hydrogen Evolution Reaction Catalysts.","authors":"Jiaqian Wang, Xiaojuan Hu, Ying Jiang, Wentao Yuan, Hangsheng Yang, Zhong-Kang Han, Yong Wang","doi":"10.1021/jacsau.5c00339","DOIUrl":"10.1021/jacsau.5c00339","url":null,"abstract":"<p><p>Data-driven approaches are increasingly vital in the field of catalyst design, significantly accelerating catalyst development. However, the mechanisms and rules underlying these approaches often lack transparency, potentially leading to unreliable outcomes due to an insufficient understanding of the specific processes involved. Here, we developed a method that combines analytical learning with constrained data mining techniques to not only identify high-performance materials but also elucidate the optimization pathways for enhancing their performance. Using this method, we screened over a thousand potential catalysts, identifying top-performing single-atom catalysts for the hydrogen evolution reaction and mapping out optimization pathways to progressively improve performance. Notably, our findings suggest that decisions aimed at enhancing material performance, when based on tuning key factors identified from entire data sets, can be misleading. Instead, a more effective strategy is to make decisions through a systematic, step-by-step analysis of subgroup data sets, specifically focusing on subsets of high-performance materials that exhibit common characteristics. This approach enhances both the development of knowledge from data and the trustworthiness of the results, offering new insights for advancing data-driven approaches in the rational design of material properties.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2762-2769"},"PeriodicalIF":8.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510134","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":"Identifying Key Factors Influencing Advanced Hydrogen Evolution Reaction Catalysts","authors":"Jiaqian Wang,&nbsp;Xiaojuan Hu,&nbsp;Ying Jiang,&nbsp;Wentao Yuan,&nbsp;Hangsheng Yang,&nbsp;Zhong-Kang Han* and Yong Wang*,&nbsp;","doi":"10.1021/jacsau.5c0033910.1021/jacsau.5c00339","DOIUrl":"https://doi.org/10.1021/jacsau.5c00339https://doi.org/10.1021/jacsau.5c00339","url":null,"abstract":"<p >Data-driven approaches are increasingly vital in the field of catalyst design, significantly accelerating catalyst development. However, the mechanisms and rules underlying these approaches often lack transparency, potentially leading to unreliable outcomes due to an insufficient understanding of the specific processes involved. Here, we developed a method that combines analytical learning with constrained data mining techniques to not only identify high-performance materials but also elucidate the optimization pathways for enhancing their performance. Using this method, we screened over a thousand potential catalysts, identifying top-performing single-atom catalysts for the hydrogen evolution reaction and mapping out optimization pathways to progressively improve performance. Notably, our findings suggest that decisions aimed at enhancing material performance, when based on tuning key factors identified from entire data sets, can be misleading. Instead, a more effective strategy is to make decisions through a systematic, step-by-step analysis of subgroup data sets, specifically focusing on subsets of high-performance materials that exhibit common characteristics. This approach enhances both the development of knowledge from data and the trustworthiness of the results, offering new insights for advancing data-driven approaches in the rational design of material properties.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2762–2769 2762–2769"},"PeriodicalIF":8.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337964","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 Remarkable Catalyst-Free Photochemical Alkene Hydrophosphination with Bis(trimethylsilyl)phosphonite.","authors":"Eloïse Bréger, Jade Dussart-Gautheret, Rachid Taakili, Fabien Fontaine-Vive, Christopher C Cummins, Rachid Benhida","doi":"10.1021/jacsau.5c00444","DOIUrl":"10.1021/jacsau.5c00444","url":null,"abstract":"<p><p>This publication delves into a comprehensive exploration of a new synthetic route to functionalized phosphorus-derived compounds. Bis-(trimethylsilyl)-phosphonite HP-(OSiMe₃)₂, prepared in a high yield from H₃PO₂, was found to be an excellent reagent for hydrophosphination of activated, unactivated, and amino acid-derived olefins under UV irradiation and catalyst-, solvent- and glovebox-free conditions. The resulting phosphorus trivalent compounds have been subjected to postfunctionalization, leading to the formation of <i>H</i>-phosphinate, phosphonate, and thiophosphonate end products in good to excellent yields. With a combination of experimental and theoretical calculations, the mechanism for this hydrophosphination reaction has been investigated, revealing a radical process.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2861-2870"},"PeriodicalIF":8.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510102","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 Remarkable Catalyst-Free Photochemical Alkene Hydrophosphination with Bis(trimethylsilyl)phosphonite","authors":"Eloïse Bréger,&nbsp;Jade Dussart-Gautheret,&nbsp;Rachid Taakili,&nbsp;Fabien Fontaine-Vive,&nbsp;Christopher C. Cummins* and Rachid Benhida*,&nbsp;","doi":"10.1021/jacsau.5c0044410.1021/jacsau.5c00444","DOIUrl":"https://doi.org/10.1021/jacsau.5c00444https://doi.org/10.1021/jacsau.5c00444","url":null,"abstract":"<p >This publication delves into a comprehensive exploration of a new synthetic route to functionalized phosphorus-derived compounds. Bis(trimethylsilyl)phosphonite HP(OSiMe₃)₂, prepared in a high yield from H₃PO₂, was found to be an excellent reagent for hydrophosphination of activated, unactivated, and amino acid-derived olefins under UV irradiation and catalyst-, solvent- and glovebox-free conditions. The resulting phosphorus trivalent compounds have been subjected to postfunctionalization, leading to the formation of <i>H</i>-phosphinate, phosphonate, and thiophosphonate end products in good to excellent yields. With a combination of experimental and theoretical calculations, the mechanism for this hydrophosphination reaction has been investigated, revealing a radical process.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2861–2870 2861–2870"},"PeriodicalIF":8.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338160","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":"Direct O₂ Activation by Ligand-Constrained Pnictogen Complexes: Contrasting Mechanisms and OAT Reactivity across the P, Sb, and Bi Triad.","authors":"Sung Gyu Kim, Jinrok Oh, Dongyoung Kim, Dae Eui Choi, Seung Jun Hwang","doi":"10.1021/jacsau.5c00371","DOIUrl":"10.1021/jacsau.5c00371","url":null,"abstract":"<p><p>Electronic structure-reactivity relationships are fundamental to advancing the redox chemistry of main-group elements. Herein, we investigate a series of planarized <i>C</i> _2v pnictogen complexes (Pn = P, Sb, Bi) to correlate their electronic structures with reactivity trends across the pnictogen group. Through single-crystal X-ray diffraction, UV-vis spectroscopy, electrochemical measurements, and density functional theory (DFT) calculations, we demonstrate a systematic reduction in HOMO-LUMO gap progressing from phosphorus to bismuth, accompanied by enhanced stabilization of the nucleophilic lone pair. Oxygen atom transfer (OAT) reactivity, probed using triphenylpnictines (PnPh₃, Pn = P, Sb, Bi) as mechanistic and thermodynamic reporters, reveals distinctive oxidation pathways. The phosphorus complex (<b>1</b>) undergoes a four-electron oxidation to yield a dioxophosphorane species, whereas the heavier congeners (<b>2</b> and <b>3</b>) generate monooxygenated Pn=O products exclusively. This mechanistic divergence is attributed to pronounced orbital contraction in heavier pnictogens, which stabilizes the lone pair and attenuates its participation in multielectron redox processes. Computational and experimental analyses corroborate these trends, with Hammett studies and p<i>K</i> _a calculations of peroxo intermediates revealing enhanced nucleophilicity of the oxygen center with increasing pnictogen atomic weight, thereby influencing the OAT mechanism. These findings provide fundamental insights into periodic trends governing oxidation chemistry and demonstrate how strategic ligand design can modulate pnictogen-based multielectron reactivity. The broader implications extend to small-molecule activation and catalysis, offering a predictive framework for designing advanced redox-active main-group systems.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2779-2791"},"PeriodicalIF":8.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510112","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}