ACS Central Science最新文献

{"title":"Transforming Aluminum-Ion Batteries with Recyclable Solid-State Electrolytes","authors":"Zhitong Xiao,&nbsp; and ,&nbsp;Quanquan Pang​​,&nbsp;","doi":"10.1021/acscentsci.5c0022410.1021/acscentsci.5c00224","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00224https://doi.org/10.1021/acscentsci.5c00224","url":null,"abstract":"<p >A recyclable solid-state electrolyte enabled by a novel aluminum fluoride framework enhances aluminum-ion battery longevity, safety, and cost-efficiency.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"180–182 180–182"},"PeriodicalIF":12.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct (LC-)MS Identification of Regioisomers from C–H Functionalization by Partial Isotopic Labeling","authors":"Christopher A. Sojdak,&nbsp;David A. Polefrone,&nbsp;Hriday M. Shah,&nbsp;Cassandra D. Vu,&nbsp;Brandon J. Orzolek,&nbsp;Pedro M. Jimenez Antenucci,&nbsp;Micah Valadez Bush and Marisa C. Kozlowski*,&nbsp;","doi":"10.1021/acscentsci.4c0176510.1021/acscentsci.4c01765","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01765https://doi.org/10.1021/acscentsci.4c01765","url":null,"abstract":"<p >C–H functionalization of complex substrates is highly enabling in total synthesis and in the development of late-stage drug candidates. Much work has been dedicated to developing new methods as well as predictive modeling to accelerate route scouting. However, workflows to identify regioisomeric products are arduous, typically requiring chromatographic separation and/or nuclear magnetic resonance spectroscopy analysis. In addition, most reports focus on major products or do not assign regioisomeric products, which biases predictive models constructed from such data. Herein, we present a novel approach to complex reaction analysis utilizing partial deuterium labels, which enables direct product identification via liquid chromatography–mass spectrometry. When combined with spectral deconvolution, the method generates product ratios while circumventing chromatography altogether. Competitive kinetic isotope effects can also be determined. The resultant data are expected to be useful in the construction of predictive models across several dimensions including reaction selectivity, the impact of structure on mechanism, and mass spectral ionization patterns and expedite the identification of drug metabolites.</p><p >Partial isotopic labels allow direct identification of regioisomers via their distinct isotopic distributions. Alternately, spectral deconvolution of unseparated mixtures delivers regioisomer ratios.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"272–278 272–278"},"PeriodicalIF":12.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01765","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stars by the Pocketful","authors":"Clara E. Lavis,&nbsp; and ,&nbsp;Luke D. Lavis​,&nbsp;","doi":"10.1021/acscentsci.5c0022310.1021/acscentsci.5c00223","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00223https://doi.org/10.1021/acscentsci.5c00223","url":null,"abstract":"<p >SWIR dyes─The Eras Tour. This love story between chemistry and biology shines.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"183–186 183–186"},"PeriodicalIF":12.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pumping Iron for Tuberculosis Diagnostics","authors":"Abdulai Zigli,&nbsp; and ,&nbsp;Benjamin M. Swarts​,&nbsp;","doi":"10.1021/acscentsci.5c0013310.1021/acscentsci.5c00133","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00133https://doi.org/10.1021/acscentsci.5c00133","url":null,"abstract":"<p >Synthetic mycobactin−fluorophore conjugates exploit the mycobacterial iron acquisition pathway to enable sensitive fluorogenic detection of <i>Mycobacterium tuberculosis</i>.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"190–192 190–192"},"PeriodicalIF":12.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemically Informed Coarse-Graining of Electrostatic Forces in Charge-Rich Biomolecular Condensates","authors":"Andrés R. Tejedor,&nbsp;Anne Aguirre Gonzalez,&nbsp;M. Julia Maristany,&nbsp;Pin Yu Chew,&nbsp;Kieran Russell,&nbsp;Jorge Ramirez,&nbsp;Jorge R. Espinosa* and Rosana Collepardo-Guevara*,&nbsp;","doi":"10.1021/acscentsci.4c0161710.1021/acscentsci.4c01617","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01617https://doi.org/10.1021/acscentsci.4c01617","url":null,"abstract":"<p >Biomolecular condensates composed of highly charged biomolecules, such as DNA, RNA, chromatin, and nucleic-acid binding proteins, are ubiquitous in the cell nucleus. The biophysical properties of these charge-rich condensates are largely regulated by electrostatic interactions. Residue-resolution coarse-grained models that describe solvent and ions implicitly are widely used to gain mechanistic insights into the biophysical properties of condensates, offering transferability, computational efficiency, and accurate predictions for multiple systems. However, their predictive accuracy diminishes for charge-rich condensates due to the implicit treatment of solvent and ions. Here, we present Mpipi-Recharged, a residue-resolution coarse-grained model that improves the description of charge effects in biomolecular condensates containing disordered proteins, multidomain proteins, and/or disordered single-stranded RNAs. Mpipi-Recharged introduces a pair-specific asymmetric Yukawa electrostatic potential, informed by atomistic simulations. We show that this asymmetric coarse-graining of electrostatic forces captures intricate effects, such as charge blockiness, stoichiometry variations in complex coacervates, and modulation of salt concentration, without requiring explicit solvation. Mpipi-Recharged provides excellent agreement with experiments in predicting the phase behavior of highly charged condensates. Overall, Mpipi-Recharged improves the computational tools available to investigate the physicochemical mechanisms regulating biomolecular condensates, enhancing the scope of computer simulations in this field.</p><p >Mpipi-Recharged is a residue-resolution coarse-grained model that innovatively treats screened electrostatic interactions, improving predictions for charged biomolecular condensates and ensuring computational efficiency.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"302–321 302–321"},"PeriodicalIF":12.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atroposelective Construction of Biaryls Enabled by a Ni(II)-Catalyzed Aerobic Oxidation Strategy","authors":"Chandini Pradhan,&nbsp; and ,&nbsp;Benudhar Punji​,&nbsp;","doi":"10.1021/acscentsci.5c0016910.1021/acscentsci.5c00169","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00169https://doi.org/10.1021/acscentsci.5c00169","url":null,"abstract":"<p >Enantioriched biaryls synthesis via aerobic oxidative cross-coupling of arenes involving bioinspired oxygen activation by Ni(II).</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"187–189 187–189"},"PeriodicalIF":12.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Natural Resorcylic Acid Lactones as Novel Potent Copper Ionophores Covalently Targeting PRDX1 to Induce Cuproptosis for Triple-Negative Breast Cancer Therapy","authors":"Li Feng,&nbsp;Ti-Zhi Wu,&nbsp;Xin-Rui Guo,&nbsp;Yun-Jie Wang,&nbsp;Xin-Jia Wang,&nbsp;Shao-Xuan Liu,&nbsp;Rui Zhang,&nbsp;Yi Ma,&nbsp;Ning-Hua Tan*,&nbsp;Jin-Lei Bian* and Zhe Wang*,&nbsp;","doi":"10.1021/acscentsci.4c0218810.1021/acscentsci.4c02188","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02188https://doi.org/10.1021/acscentsci.4c02188","url":null,"abstract":"<p >Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. Cuproptosis, a novel identified cell death form, is triggered by the direct binding of copper to lipoylated components of the tricarboxylic acid cycle. Identifying new effective drug targets and copper ionophores inducing cuproptosis for TNBC therapy is an urgent clinical need. In this study, a total of 24 resorcylic acid lactones (RALs, <b>1</b>–<b>24</b>), including 9 previously unreported ones, were isolated from the endophyte <i>Ilyonectria</i> sp. Various assays demonstrated that pochonin D (<b>16</b>, PoD) effectively inhibited the proliferation of TNBC cells <i>in vivo</i> and <i>in vitro</i>. Further investigations, including transcriptomics, proteomics, bioinformatics analysis, CMap, OTTER, clinical samples, and the use of PoD as molecular probe, revealed that PRDX1 is associated with cuproptosis and served as a potential target in TNBC. Mechanistically, PRDX1 was involved in the process of cuproptosis, and PoD bound to the Cys173 site of PRDX1, inhibited its enzymatic activity, and intervened with cuproptosis, thereby exerting anti-TNBC activity. Our study revealed that PRDX1 is not only a promising biomarker associated with cuproptosis but also a therapeutic target for TNBC, and PoD is a novel copper ionophore capable of inducing cuproptosis in TNBC cells by targeting PRDX1.</p><p >24 RALs were identified from <i>Ilyonectria</i> sp., in which PoD (<b>16</b>) exhibited potent anti-TNBC activity. PoD was used as probe to identify PRDX1 as a drug target involved in cuproptosis for TNBC therapy.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"357–370 357–370"},"PeriodicalIF":12.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bayesian Optimization over Multiple Experimental Fidelities Accelerates Automated Discovery of Drug Molecules","authors":"Matthew A. McDonald,&nbsp;Brent A. Koscher,&nbsp;Richard B. Canty,&nbsp;Jason Zhang,&nbsp;Angelina Ning and Klavs F. Jensen*,&nbsp;","doi":"10.1021/acscentsci.4c0199110.1021/acscentsci.4c01991","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01991https://doi.org/10.1021/acscentsci.4c01991","url":null,"abstract":"<p >Different experiments of differing fidelities are commonly used in the search for new drug molecules. In classic experimental funnels, libraries of molecules undergo sequential rounds of virtual, coarse, and refined experimental screenings, with each level balanced between the cost of experiments and the number of molecules screened. Bayesian optimization offers an alternative approach, using iterative experiments to locate optimal molecules with fewer experiments than large-scale screening, but without the ability to weigh the costs and benefits of different types of experiments. In this work, we combine the multifidelity approach of the experimental funnel with Bayesian optimization to search for drug molecules iteratively, taking full advantage of different types of experiments, their costs, and the quality of the data they produce. We first demonstrate the utility of the multifidelity Bayesian optimization (MF-BO) approach on a series of drug targets with data reported in ChEMBL, emphasizing what properties of the chemical search space result in substantial acceleration with MF-BO. Then we integrate the MF-BO experiment selection algorithm into an autonomous molecular discovery platform to illustrate the prospective search for new histone deacetylase inhibitors using docking scores, single-point percent inhibitions, and dose–response IC₅₀ values as low-, medium-, and high-fidelity experiments. A chemical search space with appropriate diversity and fidelity correlation for use with MF-BO was constructed with a genetic generative algorithm. The MF-BO integrated platform then docked more than 3,500 molecules, automatically synthesized and screened more than 120 molecules for percent inhibition, and selected a handful of molecules for manual evaluation at the highest fidelity. Many of the molecules screened have never been reported in any capacity. At the end of the search, several new histone deacetylase inhibitors were found with submicromolar inhibition, free of problematic hydroxamate moieties that constrain the use of current inhibitors.</p><p >Potential new drug molecules are automatically generated, synthesized, and tested for potency with assays of differing fidelities in each iteration of a batched Bayesian optimization campaign.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"346–356 346–356"},"PeriodicalIF":12.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directed Gas-Phase Formation of Azulene (C10H8): Unraveling the Bottom-Up Chemistry of Saddle-Shaped Aromatics","authors":"Zhenghai Yang,&nbsp;Kazuumi Fujioka,&nbsp;Galiya R. Galimova,&nbsp;Iakov A. Medvedkov,&nbsp;Shane J. Goettl,&nbsp;Rui Sun*,&nbsp;Alexander M. Mebel* and Ralf I. Kaiser*,&nbsp;","doi":"10.1021/acscentsci.4c0160610.1021/acscentsci.4c01606","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01606https://doi.org/10.1021/acscentsci.4c01606","url":null,"abstract":"<p >The azulene (C₁₀H₈) molecule, the simplest polycyclic aromatic hydrocarbon (PAH) carrying a fused seven- and five-membered ring, is regarded as a fundamental molecular building block of saddle-shaped carbonaceous nanostructures such as curved nanographenes in the interstellar medium. However, an understanding of the underlying gas-phase formation mechanisms of this nonbenzenoid 10π-Hückel aromatic molecule under low-temperature conditions is in its infancy. Here, by merging crossed molecular beam experiments with electronic structure calculations and molecular dynamics simulations, our investigations unravel an unconventional low-temperature, barrierless route to azulene via the reaction of the simplest organic radical, methylidyne (CH), with indene (C₉H₈) through ring expansion. This reaction might represent the initial step toward to the formation of saddle-shaped PAHs with seven-membered ring moieties in hydrocarbon-rich cold molecular clouds such as the Taurus Molecular Cloud-1 (TMC-1). These findings challenge conventional wisdom that molecular mass growth processes to nonplanar PAHs, especially those containing seven-membered rings, operate only at elevated pressure and high-temperature conditions, thus affording a versatile low-temperature route to contorted aromatics in our galaxy.</p><p >The azulene (C₁₀H₈) molecule, a fundamental molecular building block of saddle-shaped aromatics, is formed for the first time under single collision conditions.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"322–330 322–330"},"PeriodicalIF":12.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Collagen Triple Helix without the Superhelical Twist","authors":"Mark A. B. Kreutzberger,&nbsp;Le Tracy Yu,&nbsp;Thi H. Bui,&nbsp;Maria C. Hancu,&nbsp;Michael D. Purdy,&nbsp;Tomasz Osinski,&nbsp;Peter M. Kasson,&nbsp;Edward H. Egelman* and Jeffrey D. Hartgerink*,&nbsp;","doi":"10.1021/acscentsci.5c0001810.1021/acscentsci.5c00018","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00018https://doi.org/10.1021/acscentsci.5c00018","url":null,"abstract":"<p >Collagens are ubiquitous in biology: functioning as the backbone of the extracellular matrix, forming the primary structural components of key immune system complexes, and fulfilling numerous other structural roles in a variety of systems. Despite this, there is limited understanding of how triple helices, the basic collagen structural units, pack into collagenous assemblies. Here we use a peptide self-assembly system to design collagenous assemblies based on the C1q collagen-like region. Using cryo-EM we solved a structure of one assembly to 3.5 Å resolution and built an atomic model. From this, we identify a triple helix conformation with no superhelical twist, starkly in contrast to the canonical right-handed triple helix. This nontwisting region allows for unique hydroxyproline stacking between adjacent triple helices and also results in the formation of an exposed cavity with rings of hydrophobic amino acids packed symmetrically. We find no precedent for such an arrangement of collagen triple helices and designed assemblies with substituted amino acids in various locations to probe key stabilizing amino acid interactions in the complex. The stability of these altered complexes behaves as predicted by our atomic model. Our findings, combined with the extremely limited experimental structural data on triple helix packing in the literature, suggest that collagen and collagen-like assemblies may adopt a far more varied conformational landscape than previously appreciated. We hypothesize that this is particularly likely in packed assemblies of triple helices, adjacent to the termini of these helices and at discontinuities in the required Xaa-Yaa-Gly repeating primary sequence, a discontinuity found in the majority of this class of proteins and in many collagen-associated diseases.</p><p >The atomic structure of the N-terminal domain of C1q was solved using cryo-EM. This revealed collagen triple helices lacking the canonical superhelical twist, a folding motif not previously observed.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 2","pages":"331–345 331–345"},"PeriodicalIF":12.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}