ACS Central Science最新文献_第4页

Solvent-Mediated Phase Propagation Governs Excitonic Heterogeneity in Chiral Fibrils 溶剂介导的相传播控制手性原纤维中的激子非均质性

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-09-23 Epub Date: 2026-08-28 DOI: 10.1021/acscentsci.6c00969

Philip Daniel Maret, Brijith Thomas, Mahesh Hariharan

{"title":"Solvent-Mediated Phase Propagation Governs Excitonic Heterogeneity in Chiral Fibrils","authors":"Philip Daniel Maret, Brijith Thomas, Mahesh Hariharan","doi":"10.1021/acscentsci.6c00969","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00969","url":null,"abstract":"Phase propagation and phase separation in biomolecularcondensateshave emerged as key concepts for understanding the nonequilibriumevolution of functional assemblies, yet achieving analogous processesin soft molecular aggregates remains challenging. Here, we directlyvisualize phase propagation between coexisting J-type coupled andexcimer-emitting domains within individual crystalline fibrils ofa chiral perylenediimide dimer (RCy-PDI2) using fluorescencelifetime imaging microscopy (FLIM). FLIM analysis revealed heterogeneousdistribution of short (τblue ≈1.5 ns) and long (τgreen ≈8 ns) fluorescence lifetime components in a single aggregate fibril.Time-dependent FLIM measurements facilitated the understanding ofphase propagation and shrinkage-induced fibril fracture in the aggregatefibrils. Steady-state and chiroptical measurements of (RCy-PDI2) aggregate fibrils indicated the presence of J-type aggregateformation and excimer emission. Three-dimensional electron diffraction(3D ED) reveals a toluene-intercalated structure enforcing a V-shapedgeometry (interplanar angle: 26.3°), enabling strong Coulombiccoupling (Jc = -55 to -73 meV) consistentwith J-type interactions. Toluene diffusion and detrapping drive structuralrelaxation, converting J-type domains into excimer-emitting regionswithin the same fibril, establishing a direct structural basis forexcitonic state selection. This work correlates excitonic heterogeneitywith phase propagation, expanding our understanding of the role ofsolvent diffusion and molecular stacking in the development of functionalsupramolecular materials.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 9","pages":"1468–1476"},"PeriodicalIF":11.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149022711","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

Correction to “Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression” 对“哌隆明调节TRPV2变构拮抗剂损害胶质母细胞瘤进展”的更正

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-09-23 Epub Date: 2026-08-12 DOI: 10.1021/acscentsci.6c01291

João Conde, Ruth A. Pumroy, Charlotte Baker, Tiago Rodrigues, Ana Guerreiro, Bárbara B. Sousa, Marta C. Marques, Bernardo P. de Almeida, Sohyon Lee, Elvira P. Leites, Daniel Picard, Amrita Samanta, Sandra H. Vaz, Florian Sieglitz, Maike Langini, Marc Remke, Rafael Roque, Tobias Weiss, Michael Weller, Yuhang Liu, Seungil Han, Francisco Corzana, Vanessa A. Morais, Cláudia C. Faria, Tânia Carvalho, Panagis Filippakopoulos, Berend Snijder, Nuno L. Barbosa-Morais, Vera Y. Moiseenkova-Bell, Gonçalo J. L. Bernardes

引用次数: 0

Chemical Distance-Based Acceleration of Large Library Docking with ChemSTEP 基于化学距离的大型文库与ChemSTEP对接加速

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-07-20 DOI: 10.1021/acscentsci.6c00396

Olivier Mailhot, Katie L. Holland, Lu Paris, Dmytro S. Radchenko, Yurii S. Moroz, John J. Irwin, Brian K. Shoichet

{"title":"Chemical Distance-Based Acceleration of Large Library Docking with ChemSTEP","authors":"Olivier Mailhot, Katie L. Holland, Lu Paris, Dmytro S. Radchenko, Yurii S. Moroz, John J. Irwin, Brian K. Shoichet","doi":"10.1021/acscentsci.6c00396","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00396","url":null,"abstract":"While make-on-demandlibraries now span trillions of molecules,full library docking struggles beyond a few billion, motivating prioritizationthat recovers top-scoring compounds while evaluating only a fractionof a library. Here we introduce a similarity-based prioritizationapproach, ChemSTEP, and define the effective size of a library treatedby any prioritization algorithm, Neff. ChemSTEP docks arepresentative seed set, selects diverse high-scoring “beacons”,and iteratively traverses the library through cycles of beacon selection,similarity search, and docking. Retrospectively on eight targets,ChemSTEP recovered over 75% of high-scoring compounds while dockingless than 5% of a library. We then tested ChemSTEP prospectively againstAmpC β-lactamase using a 13.2 billion molecule library. BecauseAmpC recognizes negatively charged inhibitors, we explicitly dockedall 360 million library anions, synthesizing and testing 241 high-rankingones in parallel to the ChemSTEP 13.2B run. Compared with previousdocking of 99 million and 1.7 billion molecules against AmpC, the13.2 billion library had higher hit-rates (2% vs 25% vs 37%, respectively)and found more potent compounds. Meanwhile, ChemSTEP retrieved 80%of the 241 high-ranking compounds within the first 0.5% docked. Trillion-moleculelibraries might be in reach with this approach.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 8","pages":"1178–1194"},"PeriodicalIF":11.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815792","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

Electric-Field Catalysis of Diels–Alder Reactions 电场催化Diels-Alder反应

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-07-24 DOI: 10.1021/acscentsci.6c00852

Bing-Ru Shao, Shen-Yi Guo, Miguel Paraja, Qing-Xia Zhang, Augustina Jozeliu̅naitė, Naomi Sakai, Stefan Matile

{"title":"Electric-Field Catalysis of Diels–Alder Reactions","authors":"Bing-Ru Shao, Shen-Yi Guo, Miguel Paraja, Qing-Xia Zhang, Augustina Jozeliu̅naitė, Naomi Sakai, Stefan Matile","doi":"10.1021/acscentsci.6c00852","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00852","url":null,"abstract":"The dream to catalyzereactions with externally appliedelectricfields is so obvious and so promising that it has attracted immensescientific attention. The Diels–Alder (DA) reaction has becomethe primary reaction to elaborate on this dream, but electric-fieldcatalysis (EFC) of DA reactions under practical organic synthesisconditions remained impossible. The objective of this study was tochallenge the emerging principles of scalable EFC in microfluidiccapacitors with this holy grail in the field. Functional Helmholtzlayers are assembled to translate applied electric fields into effectiveelectric fields that are, according to chronoamperometry, strong enoughfor the EFC. Yields increase nonlinearly from 0% up to 90% with appliedvoltage. In chiral cationic Helmholtz layers assembled from polyarginines,benzylated quinines, or ammonium binaphthyls, enantioselectivity upto 31% ee is obtained. These results demonstratethat the emerging principles of EFC in microfluidic capacitors passthe ultimate test in the field with distinction: Besides realizingDA-EFC with externally applied electric fields under practical conditions,this study also introduces chiral Helmholtz layers as (i) the primarycatalysts, with an impressive efficiency of EC50 = 0.2mol %, and (ii) the unique source of chirality for asymmetric EFC.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 8","pages":"1165–1177"},"PeriodicalIF":11.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815824","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

A Tumor-Microenvironment-Responsive Chemically Masked IL-2 Prodrug Potentiates PD-1 Checkpoint Blockade and Elicits Robust Antitumor Efficacy 肿瘤微环境反应性化学掩盖IL-2前药增强PD-1检查点阻断并引发强大的抗肿瘤功效

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-08-05 DOI: 10.1021/acscentsci.6c00344

Linzhi Tan, Yunwen Yang, Kerui Zhao, Jingjing Zhou, Xin Wang, Xingyu Zhao, Qiang Lu, Junyu Lin, Yijie Zhao, Yushun Tian, Yong Wang, Chao Zhong, Tao Liu

{"title":"A Tumor-Microenvironment-Responsive Chemically Masked IL-2 Prodrug Potentiates PD-1 Checkpoint Blockade and Elicits Robust Antitumor Efficacy","authors":"Linzhi Tan, Yunwen Yang, Kerui Zhao, Jingjing Zhou, Xin Wang, Xingyu Zhao, Qiang Lu, Junyu Lin, Yijie Zhao, Yushun Tian, Yong Wang, Chao Zhong, Tao Liu","doi":"10.1021/acscentsci.6c00344","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00344","url":null,"abstract":"Interleukin-2 (IL-2)is a potent mediator of T-cell activationwith significant potential for cancer immunotherapy, yet its clinicalutility is severely constrained by its narrow therapeutic window.Here we report a chemically masked IL-2 prodrug (Cm-proIL2) that enablestumor-microenvironment-responsive cytokine activation through tumor-associatedprotease cleavage. Site-specific conjugation of a poly(ethylene glycol)(PEG) moiety selectively masks peripheral receptor engagement, whilePEG removal within the tumor microenvironment restores IL-2 receptorbinding and reduces molecular size, thereby enhancing intratumorallymphocyte penetration and effector T cell functionality. Buildingon this modular platform, we further engineered a PD-1-targeted nanobodyfusion, PD1-Cm-proIL2, to enable the cis delivery of IL-2 activityto PD-1+ tumor-infiltrating T cells. PD1-Cm-proIL2 inducesrobust antitumor immunity, resulting in complete tumor regressionand durable protection upon tumor rechallenge in a murine colorectalcancer model. Together, these findings demonstrate the feasibilityof chemically masked, tumor-responsive cytokine activation as a strategyfor improving the therapeutic index of IL-2-based immunotherapies.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 8","pages":"1223–1236"},"PeriodicalIF":11.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148810206","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

Spatial Evolution of Antimicrobial Metallopolymers toward the Main Chain Topology 抗菌金属聚合物主链拓扑结构的空间演化

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-06-19 DOI: 10.1021/acscentsci.6c00694

Md Waliullah Hossain, Marsh Kral, Aylin Feuerstein, Swagatam Barman, Alimi Abiodun, Markus Gallei, Chao Cai, André Schäfer, Chuanbing Tang

{"title":"Spatial Evolution of Antimicrobial Metallopolymers toward the Main Chain Topology","authors":"Md Waliullah Hossain, Marsh Kral, Aylin Feuerstein, Swagatam Barman, Alimi Abiodun, Markus Gallei, Chao Cai, André Schäfer, Chuanbing Tang","doi":"10.1021/acscentsci.6c00694","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00694","url":null,"abstract":"Synthetic polymersand peptides with spatial controlhave emergedas effective molecular agents for addressing antimicrobial resistance(AMR). We report on one of the first kinds of studies on how spatialcompositions in cationic metallopolymers can be tuned to control theirantimicrobial efficacy. As a representative, the evolution of cobaltoceniumcation from side chain to main chain has shown drastic impacts onpolymer–cell interactions and consequential killing of microbes.A main-chain cobaltocenium polymer exhibited broad-spectrum activityagainst multidrug-resistant (MDR) bacteria, primarily targeting bacterialcell membranes and outer leaflets. The polymer also showed a strongefficacy in treating mature biofilms across multiple bacterial strains.Resistance development was evaluated over 20 passages, with no detectableresistance. Overall, these findings reveal spatial control of cationiccenters in metallopolymers as a unique molecular platform for combatingMDR pathogens and alleviating the AMR burden on global healthcaresettings.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 8","pages":"1099–1109"},"PeriodicalIF":11.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815803","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

Controlled Acidity Gradients Enable CO2 Reduction to Formic Acid (Not Formate) by Molecular Electrocatalysts 控制酸度梯度使CO2通过分子电催化剂还原为甲酸（非甲酸）

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-07-17 DOI: 10.1021/acscentsci.6c00571

Sergio Fernández, Pablo Fernandez, Amanda I. Arnoff, Elizabeth A. Scholer, Charlotte L. Montgomery, Jillian L. Dempsey, Thomas E. Mallouk, René Lopez, Alexander J. M. Miller

引用次数: 0

Correction to “Propellane Alkaloid Biosynthesis and Total Synthesis via Interrupted Reaction Pathways” 修正“通过中断反应途径合成丙烷生物碱和全合成”

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-07-29 DOI: 10.1021/acscentsci.6c01223

John M. Billingsley, Jiaming Ding, Allison T. Hands, Kanji Niwa, Nathan J. Adamson, Lukas A. Wein, Bruno Perlatti, Neil K. Garg, Yi Tang

引用次数: 0

A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly 二聚体蛋白- rna胶促进多价eIF4A-RNA组装

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-08-01 DOI: 10.1021/acscentsci.6c00662

Jie Liu, Megan K. Moore, Kevin Lou, Douglas R. Wassarman, Abolfazl Arab, Samuel Ojeda, Barbara Karakyriakou, Ann-Sophie Koglin, Christopher J. Ott, Luke A. Gilbert, Kevan M. Shokat

{"title":"A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly","authors":"Jie Liu, Megan K. Moore, Kevin Lou, Douglas R. Wassarman, Abolfazl Arab, Samuel Ojeda, Barbara Karakyriakou, Ann-Sophie Koglin, Christopher J. Ott, Luke A. Gilbert, Kevan M. Shokat","doi":"10.1021/acscentsci.6c00662","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00662","url":null,"abstract":"Ligand dimerizationrepresents a powerful strategy toenhance avidity,potency, and selectivity. Leveraging the natural-product molecularglue rocaglamide (RocA), we identified BisRoc, a dimeric rocaglateligand that potently and durably suppresses translation and exhibitsgreater specificity across a cancer cell line panel than the monomericRocA. CRISPRi screening revealed that BisRoc activity is influencedby cellular context, including IFITM-mediated uptake, ABC-type effluxtransporters, and the translation initiation factor eIF4A2. Mechanisticstudies showed that the paralogs eIF4A1 and eIF4A2 are differentiallysensitive to BisRoc-induced dimerization. Owing to the presence ofmultiple binding sites on RNAs, BisRoc-bridged eIF4A-RNA motifs assembleinto higher-order complexes that promote stress-granule formationmore efficiently than monomeric RocA. Given the widespread multivalencyof RNA-RBP interactions, this ligand dimerization strategy may beextended to modulate the higher-order assembly of other RNA-bindingproteins.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 8","pages":"1195–1206"},"PeriodicalIF":11.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815622","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

Design Rules for Tuning Thermal Lifetimes of Arylazopyrazole Photoswitches 调谐芳唑吡唑光开关热寿命的设计规则

IF 11.1 1区化学

ACS Central Science Pub Date : 2026-08-26 Epub Date: 2026-08-04 DOI: 10.1021/acscentsci.6c00586

Maximilian X. Tiefenbacher, Johannes C. B. Dietschreit, Simon Axelrod, Rafael Gómez-Bombarelli, Leticia González

{"title":"Design Rules for Tuning Thermal Lifetimes of Arylazopyrazole Photoswitches","authors":"Maximilian X. Tiefenbacher, Johannes C. B. Dietschreit, Simon Axelrod, Rafael Gómez-Bombarelli, Leticia González","doi":"10.1021/acscentsci.6c00586","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00586","url":null,"abstract":"Predicting thermal relaxation rates in molecular photoswitchesremains a major challenge, as competing reaction pathways and multipleelectronic states govern their isomerization dynamics. Arylazopyrazolesexemplify this complexity while offering nearly quantitative bidirectionalphotoconversion and widely tunable thermal half-lives. Here, we mapthe isomerization landscapes of nearly 30,000 arylazopyrazole derivativesusing a machine-learned interatomic potential trained on density functionaltheory data, enabling high-throughput simultaneous exploration ofadiabatic and nonadiabatic pathways. The workflow identifies minima,transition states, and minimum-energy crossing points, allowing thermalrelaxation rates to be computed at scale. Comparison with availableexperimental data demonstrates reliable prediction of absolute rateconstants. Across chemical space, we uncover clear structure-mechanism-propertyrelationships linking substituent position, pyrazole methylation,and electronic substitution patterns to mechanistic preference andoverall relaxation kinetics. These results provide practical designrules for tuning the thermal stability of arylazopyrazole photoswitchesand establish a general strategy for predicting relaxation kineticsin complex molecular switches.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 8","pages":"1246–1257"},"PeriodicalIF":11.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148815741","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