ACS Central Science最新文献

A Robust π-Conjugated Radical Cocrystal 一种鲁棒π共轭自由基共晶

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-10-05 DOI: 10.1021/acscentsci.6c01649

Han Han, Lei Fang

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Room Temperature Structures of Solvated Organic Molecules Enabled by Liquid Cell Electron Diffraction 液体电池电子衍射使溶剂化有机分子的室温结构成为可能

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-09-22 DOI: 10.1021/acscentsci.6c00603

Niko W. Vlahakis, Krzysztof Konieczny, Cameron W. Flowers, Miguel A. Garcia-Garibay, Jose A. Rodriguez

{"title":"Room Temperature Structures of Solvated Organic Molecules Enabled by Liquid Cell Electron Diffraction","authors":"Niko W. Vlahakis, Krzysztof Konieczny, Cameron W. Flowers, Miguel A. Garcia-Garibay, Jose A. Rodriguez","doi":"10.1021/acscentsci.6c00603","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00603","url":null,"abstract":"Electron diffraction(MicroED/3DED) enables atomic structuredeterminationfrom nano- or microcrystals, including dry crystalline powders ormixtures. However, radiation damage and instrument vacuum can limitthe interrogation of molecular crystals in solution at room temperature.We now present a strategy for room-temperature MicroED of organicmolecular microcrystals suspended in solution, using simple liquidcells: grid sandwiches comprised of two continuous carbon grids thatwhen pressed retain a thin liquid layer between them. In this setting,we find that some room-temperature, hydrated microcrystals are particularlyprone to electron beam radiation damage, requiring fast, low dosedata collection schemes, direct electron detectors, and multi-crystaldata collection. These approaches minimize damage of crystals in liquidcells and facilitate ab initio structures at sub-Ångstromresolution. This tactic enables study of molecular conformations andcrystalline phases that may only be accessible in a room-temperaturesolvated state.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 10","pages":"1592–1600"},"PeriodicalIF":11.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Quantifying Directedness in Chemical Reaction Networks Using Assembly Theory 用装配理论量化化学反应网络的方向性

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-09-30 DOI: 10.1021/acscentsci.6c00618

Michael Jirasek, Abhishek Sharma, Mary Wong, Jennifer Munro, Leroy Cronin

{"title":"Quantifying Directedness in Chemical Reaction Networks Using Assembly Theory","authors":"Michael Jirasek, Abhishek Sharma, Mary Wong, Jennifer Munro, Leroy Cronin","doi":"10.1021/acscentsci.6c00618","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00618","url":null,"abstract":"There is currentlyno general experimental frameworkfor determiningwhether an open-ended reaction network explores chemical space undirectedlyor with some level of directedness. Assembly Theory (AT) providesa quantitative framework for mapping experimentally observed molecularensembles into assembly space. Here we show that directedness in chemicalsystems can be quantified using two experimentally accessible observables,the exploration ratio (ER) and ensemble assembly (A). ER measuresthe fraction of the inferred joint assembly space sampled, while Aintegrates the molecular assembly index with the observed copy number.Together, these quantities distinguish undirected from directed explorationand, when applied to time-resolved data or matched controls, providea quantitative measure of transitions associated with selection. Byanalyzing peptide ensembles generated under diverse polymerizationconditions, we find that nonspecific activation conditions yield explorationratios of 0.77–0.96, whereas sequence-selective proteases yieldlower ratios of 0.51–0.75 and elevated A. These differencesare consistent across multiple environments and amino-acid combinations.The results establish ER and A as experimentally tractable metricsfor directedness in chemical reaction networks and provide a routeto quantify selection when the relevant temporal or causal contextis defined, with implications for reaction-network analysis, combinatorialsynthesis, and chemical evolution.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 10","pages":"1601–1609"},"PeriodicalIF":11.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Accelerating Reactions with Invisible Forces 用看不见的力量加速反应

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-10-01 DOI: 10.1021/acscentsci.6c01592

Ismael Díez-Pérez, Josep Puigmartí-Luis

引用次数: 0

O2-Coupled Copper–Cysteine Redox Chemistry Drives Oxidative Modifications and Higher-Order Assembly of Monomeric Transthyretin o2偶联铜-半胱氨酸氧化还原化学驱动单体转甲状腺素的氧化修饰和高阶组装

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-10-05 DOI: 10.1021/acscentsci.6c00619

Yelim Yi, Wooyeol Ryu, Bokyung Kim, Srinivasan Muniyappan, Jin Hae Kim, Kiyoung Park, Mi Hee Lim

{"title":"O2-Coupled Copper–Cysteine Redox Chemistry Drives Oxidative Modifications and Higher-Order Assembly of Monomeric Transthyretin","authors":"Yelim Yi, Wooyeol Ryu, Bokyung Kim, Srinivasan Muniyappan, Jin Hae Kim, Kiyoung Park, Mi Hee Lim","doi":"10.1021/acscentsci.6c00619","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00619","url":null,"abstract":"Copper–cysteine (Cu–Cys) coordination ispervasivein biology, yet how Cu–thiol redox chemistry engages O2 and translates into protein-level consequences remains incompletelyunderstood. Here, we establish a generalizable protein-based platformthat directly captures O2-coupled Cu(II)–Cys redoxprocesses and delineates their structural and functional outcomes.Integrated spectroscopic, mass spectrometric, and computational investigationsreveal that Cu(II) coordination to a protein Cys residue initiatesredox cycling that generates thiyl radicals and/or disulfide radicalanions. This chemically defined process drives disulfide bond formationtogether with O2-dependent oxidative transformations, producingsite-specific Cys modifications, dityrosine cross-links, and higher-orderprotein assemblies. Under these conditions, these structural changesabolish the protein’s anti-amyloidogenic activity and resultin apoptotic responses. By directly linking Cu–thiol redoxchemistry to protein oxidation and aggregation, this work establishesa fundamental chemical principle by which redox-active metal ionsgovern protein fate under aerobic conditions. More broadly, thesefindings provide a mechanistic framework for understanding how metal-mediatedoxidative chemistry contributes to protein misfolding and aggregationin human diseases.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 10","pages":"1659–1671"},"PeriodicalIF":11.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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A Chemist’s Guide to Solid-State Qubits: Diamond Color Centers as Embedded Vacancy-Centered Molecules 固态量子比特的化学家指南：钻石色中心作为嵌入的空位中心分子

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-07-27 DOI: 10.1021/acscentsci.6c00548

John Mark P. Martirez

{"title":"A Chemist’s Guide to Solid-State Qubits: Diamond Color Centers as Embedded Vacancy-Centered Molecules","authors":"John Mark P. Martirez","doi":"10.1021/acscentsci.6c00548","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00548","url":null,"abstract":"Diamond point defectsor color centers are at the cruxof solid-statequantum technology applications, from computing to sensing. Modelingmolecular qubits has advanced by leaps and bounds mainly due to theadvanced quantum mechanical (QM) tools in the arsenal of quantum chemistsfor modeling (isolated) molecular systems, which should be easilytranslatable for analogous systems in the solid state. Here, we simulatea series of diamond defects: a carbon vacancy (VC) andsecond row substitutions that are adjacent to a VC or DCVC, with D = B,N, and O, to evaluate their magnetic and optical properties. We appliedmolecular orbital principles, an embedded cluster method, and a multiconfigurationalQM theory to computationally characterize the above-mentioned defectsfor a multitude of spin, charge, and excited states. Our computationalapproach delivered high-quality QM insights that compare well withexperiments. Furthermore, with this framework, we confirm the spin-tripletsBCVC– and OCVC0 to be analogous to NCVC–, with calculated bright transitions that respectivelycorrespond to UV (3.80 eV) and blue (2.65 eV) light absorption andemission lifetimes (τ) of 2.3 and 5.6 ns, which are higher inenergy and more short-lived (and thus brighter) than that for NCVC–: green (2.26 eV), τ= 9.5 ns.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 10","pages":"1578–1591"},"PeriodicalIF":11.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Ninhydrin as a Covalent Warhead for Chemical Proteomic-Enabled Discovery and Selective Engagement of Reactive Arginines Ninhydrin作为化学蛋白质组学发现和选择性接合活性精氨酸的共价战斗部

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-09-30 DOI: 10.1021/acscentsci.6c00922

Andrew K. Ecker, Andreas Langen, Chloe S. Fields, José L. Montaño, Minh Tran, Ian B. Seiple, Balyn W. Zaro

{"title":"Ninhydrin as a Covalent Warhead for Chemical Proteomic-Enabled Discovery and Selective Engagement of Reactive Arginines","authors":"Andrew K. Ecker, Andreas Langen, Chloe S. Fields, José L. Montaño, Minh Tran, Ian B. Seiple, Balyn W. Zaro","doi":"10.1021/acscentsci.6c00922","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00922","url":null,"abstract":"Covalent moleculeshave emerged as next-generation therapeuticsand as powerful tools for perturbing fundamental biological processes.Chemical proteomic methods to screen for reactive proteinaceous aminoacids have transformed small-molecule discovery pipelines, but theirapplication remains mostly limited to sites where reactive cysteinesand lysines are present. Here we report a ninhydrin-based warheadthat selectively modifies arginine residues, thus expanding the repertoireof amino acids targetable by covalent molecules. Specifically, wedeveloped alkyne-functionalized variants of ninhydrin to establishan arginine-specific chemical proteomics platform, enabling the classificationof more than 6,800 unique reactive arginines from one cell line. Thesestudies uncovered potential modification sites on disease-relevantproteins, including reactive arginines within catalytic sites thatare essential for function and reactive arginines on proteins lackingreactive cysteines. By endowing a reversible small-molecule binderof cyclophilin A with a ninhydrin warhead, we achieved selective,covalent engagement in cell lysates and attenuation of enzymatic activity in vitro. These findings establish ninhydrin as a warheadfor studying arginine reactivity and identifying at scale argininesamenable to covalent modification.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 10","pages":"1610–1624"},"PeriodicalIF":11.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Flavorists Are Recreating Smoke to Save Europe’s Snacks 调味师正在重新创造烟雾来拯救欧洲的小吃

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-10-14 DOI: 10.1021/acscentsci.6c01681

Matt Blois

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Overcoming EGFR Resistance by Monovalent and Bident Inhibitors Targeting Cys775 靶向Cys775的单价和双抗抑制剂克服EGFR耐药性

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-09-29 DOI: 10.1021/acscentsci.6c01219

Zhengnian Li, Jie Jiang, Yaning Wang, Scott B. Ficarro, Stephen J. Collins, Tyler S. Beyett, Ilse K. Schaeffner, Isidoro Tavares, Felix H. Gottlieb, Dhiraj Suda, Prafulla C. Gokhale, Leah M. Black-Holmes, Dimitris Gazgalis, Michael J. Eck, Pasi A. Jänne, Jarrod A. Marto, Jianwei Che, Nathanael S. Gray, Tinghu Zhang

{"title":"Overcoming EGFR Resistance by Monovalent and Bident Inhibitors Targeting Cys775","authors":"Zhengnian Li, Jie Jiang, Yaning Wang, Scott B. Ficarro, Stephen J. Collins, Tyler S. Beyett, Ilse K. Schaeffner, Isidoro Tavares, Felix H. Gottlieb, Dhiraj Suda, Prafulla C. Gokhale, Leah M. Black-Holmes, Dimitris Gazgalis, Michael J. Eck, Pasi A. Jänne, Jarrod A. Marto, Jianwei Che, Nathanael S. Gray, Tinghu Zhang","doi":"10.1021/acscentsci.6c01219","DOIUrl":"https://doi.org/10.1021/acscentsci.6c01219","url":null,"abstract":"Covalent targetingof EGFR cysteine 797 by osimertinib is one ofthe most successful breakthroughs in targeted therapy, fundamentallytransforming the treatment landscape for non-small-cell lung cancer(NSCLC) patients. However, resistance driven by the mutation of C797remains a major clinical challenge. Developing novel covalent strategiesbeyond C797 targeting presents a compelling opportunity for next-generationEGFR inhibitors. We first demonstrated that cysteine 775, locateddeep within the ATP-binding pocket, is accessible by a rationallydesigned covalent molecule ZNL-3, which as the first-in-class covalentcysteine 775 inhibitor exhibited strong efficacy in osimertinib-resistantmouse models. To further enhance resilience to resistance-causingmutations, we developed a dual-warhead, bident compound YNW-1 whichcovalently targets both cysteines 775 and 797 simultaneously. YNW-1is the first intramolecular lock to exhibit balanced reactive efficiencyon both cysteines, rendering single-site mutations ineffective atconferring resistance. This study establishes the therapeutic potentialof an EGFR covalent inhibitor through unprecedented targeting of cysteine775. It also provides the first evidence that dual-cysteine engagementoffers superior efficacy to conventional covalent inhibitors by delayingthe emergence of resistance. Further optimization for clinical translationis currently ongoing in our laboratory.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 10","pages":"1647–1658"},"PeriodicalIF":11.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Late-Stage Radical (Radio)fluorosulfonylation of Amines with [19F]fluoride and [18F]fluoride [19F]氟化物和[18F]氟化物对胺的晚期自由基（无线电）氟磺化反应

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-10-28 Epub Date: 2026-09-17 DOI: 10.1021/acscentsci.6c00992

Juanjuan Wang, Yiwei Huang, Zhiwei Xiao, Yong He, Yongkang Gai, Dan Xu, Kui Xu, Zhiqing Su, Xiao Shen, Qiang Cheng

{"title":"Late-Stage Radical (Radio)fluorosulfonylation of Amines with [19F]fluoride and [18F]fluoride","authors":"Juanjuan Wang, Yiwei Huang, Zhiwei Xiao, Yong He, Yongkang Gai, Dan Xu, Kui Xu, Zhiqing Su, Xiao Shen, Qiang Cheng","doi":"10.1021/acscentsci.6c00992","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00992","url":null,"abstract":"Late-stage labelingwith fluorine-18 serves to advance clinicalcare and drug discovery via positron emission tomography (PET). Thisgoal motivates efforts to expand the accessible chemical space withtailored 18F-containing groups. Sulfamoyl fluorides arepromising because of their potential physiological stability. Existingsynthetic routes largely depend on group-transfer protocols from preformedfluorosulfonyl reagents. As a result, synthetic methods for [18F]sulfamoyl fluorides are fundamentally based on isotopeexchange. None of the methods have enabled a no-carrier-added (NCA)protocol for radiofluorosulfonylation of amines. Herein, we providenitrogen-centered radical-mediated assembling fluorosulfonylationreactions, enabling conversion of abundant NH-containing substratesinto sulfamoyl fluorides with [19F]fluoride and [18F]fluoride as an exclusive fluorine source. Our method features highfunctional group tolerance, broad NH-substrates, and an NCA radiochemicaltechnique. The initial preclinical evaluation of the freshly synthesized[18F]SUFA-flurpiridaz and its in vivo myocardialperfusion PET imaging collectively highlights the potential physiologicalstability of sulfamoyl [18F]fluoride groups and the potentialapplication of our radical radiofluorosulfonylation strategy.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 10","pages":"1625–1636"},"PeriodicalIF":11.1,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149306053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0