ACS Central Science最新文献

{"title":"Versatile Pyridinium Trifluoroborate Platform for Facile Preparation of 18F-Labeled PET Tracers in Water","authors":"Wei Li,&nbsp;Yi Li,&nbsp;Tiyi Lyu,&nbsp;Yu Chen,&nbsp;Jingjing Ma*,&nbsp;Yi Fang* and Li Zhang*,&nbsp;","doi":"10.1021/acscentsci.6c00164","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00164","url":null,"abstract":"<p >[¹⁸F]-Organotrifluoroborate salts are important radioprosthetic groups for positron emission tomography (PET) imaging. However, their application is hindered by hydrolytic instability <i>in vivo</i>. Several water-tolerant trifluoroborate scaffolds have been developed, but their multistep syntheses restrict structural diversity. Consequently, access to water-stable organotrifluoroborates with broad structural and physicochemical variation remains a challenge. Herein, a library of water-stable trifluoroborate reagents for PET tracer preparation has been developed. The reagents feature one-step synthesis, structural diversity, and high stability under aqueous conditions. The hydrolysis-resistant feature of the reagents enables the preparation of PET tracer precursors in water. Facile ¹⁸F–¹⁹F isotope exchange reactions facilitate the preparation of diverse PET tracers with pyridinium [¹⁸F]BF₃ prosthetic groups.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"824–830"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299739","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":"When AI Starts Reading Battery Papers Like a Researcher","authors":"Dian-Zhao Lin,&nbsp; and ,&nbsp;Yayuan Liu​,&nbsp;","doi":"10.1021/acscentsci.6c00760","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00760","url":null,"abstract":"<p >A new AI agent mines both text and figures from lithium-metal-battery papers, pointing toward a future where the literature itself helps guide discovery.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"738–740"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00760","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299723","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":"Mechanical Taming of Hardy–Cope Rearrangements","authors":"Matthew J. Elardo,&nbsp;Mariia Kuznetsova,&nbsp;Jason D. Kaff,&nbsp;Kiyoshi J. Colon,&nbsp;Gregory L. Olsen,&nbsp;Paul R. McGonigal* and Matthew R. Golder*,&nbsp;","doi":"10.1021/acscentsci.6c00254","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00254","url":null,"abstract":"<p >Bullvalene is a fluxional molecule that rapidly rearranges via low-barrier [3,3] sigmatropic rearrangements, allowing each of its 10 carbon atoms to exchange rapidly at room temperature, accessing all possible configurational permutations with submillisecond half-lives. We previously demonstrated that the incorporation of this fluxional core into polymeric systems imbues materials with force-responsive properties, as bullvalene’s fluxionality can reversibly “respond” to applied mechanical stress. However, direct observation of such rearrangements within the bullvalene core in response to applied force has remained elusive in soft materials because of the complexity of the resulting isomer distributions and the rapid thermal reversion of perturbed isomers. In this work, we utilize a polymer-chain-centered fluorinated bullvalene core to provide direct spectroscopic evidence of changes to the bullvalene isomer distribution in response to mechanical force. These findings position bullvalene as the first example in a unique class of mechanophores capable of undergoing <i>multiple</i> mechanochemical reactions without requiring an external stimulus for subsequent mechanochemical activity. We anticipate these results to provide key insights into the development of force-responsive materials with enhanced mechanical properties and macromolecular sensing capabilities.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"766–776"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299743","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":"Second-Generation of Deuterium-Substituted Glutamate Uptake Enhancers Exhibit Superior Drug-Like Properties in Preclinical Evaluation","authors":"Michał Abram,&nbsp;Marcin Jakubiec,&nbsp;Małgorzata Szafarz,&nbsp;Anna Rapacz,&nbsp;Magdalena Kolasa,&nbsp;Agata Faron-Górecka,&nbsp;Szczepan Mogilski,&nbsp;Kaliana Veros,&nbsp;Simran K. Gill,&nbsp;Angela Di Iacovo,&nbsp;Katarzyna Socała,&nbsp;Gniewomir Latacz,&nbsp;Joanna Karnafał,&nbsp;Krzysztof Pociecha,&nbsp;Justyna Kalinowska-Tłuścik,&nbsp;Melissa Barker-Haliski,&nbsp;Elżbieta Wyska,&nbsp;Andréia C. K. Fontana,&nbsp;Piotr Wlaź,&nbsp;Rafał M. Kamiński,&nbsp;Cristina Roseti,&nbsp;Elena Bossi,&nbsp;Karen S. Wilcox and Krzysztof Kamiński*,&nbsp;","doi":"10.1021/acscentsci.6c00080","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00080","url":null,"abstract":"<p >Strategic deuterium–hydrogen exchange applied to the first-in-class positive allosteric modulators (PAMs) of the glutamate transporter EAAT2/GLT-1, <b>(</b><i><b>R</b></i><b>)-AS-1</b> and <b>(</b><i><b>R</b></i><b>)-AS-7</b>, yielded novel analogues with improved drug-like properties. Specifically, incorporation of deuterium into the pyrrolidine-2,5-dione ring significantly prolonged the elimination half-life and increased both plasma and brain exposure in mice. These enhancements translated into more sustained antiseizure activity and a more favorable pharmacokinetic/pharmacodynamic (PK/PD) relationship. Similar to their nondeuterated counterparts, the new deuterated analogues displayed broad-spectrum antiseizure efficacy across multiple <i>in vivo</i> mouse seizure models, including maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazole (PTZ), and PTZ-induced kindling. Among these compounds, <b>d</b>_<b>6</b><b>-(</b><i><b>R</b></i><b>)-AS-7</b> demonstrated the most robust antiseizure effects and the most advantageous overall pharmacokinetic profile following both intraperitoneal and oral administration. Mechanistic studies revealed that <b>d</b>_<b>6</b><b>-(</b><i><b>R</b></i><b>)-AS-7</b> markedly enhanced glutamate uptake in COS-7 cells expressing EAAT2 as well as in primary astrocyte cultures. Furthermore, electrophysiological recordings in acute mouse hippocampal slices, together with two-electrode voltage-clamp recordings in <i>Xenopus laevis</i> oocytes expressing EAAT2, confirmed increased transporter-mediated currents. Collectively, these findings identify <b>d</b>_<b>6</b><b>-(</b><i><b>R</b></i><b>)-AS-7</b> as a potent EAAT2 PAM with improved pharmacokinetic properties and strong antiseizure efficacy, supporting its further development as a therapeutic candidate for epilepsy and other disorders associated with glutamate excitotoxicity.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"807–823"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299726","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":"From Fundamental Photophysics to Photocatalysis: Energy Gap Law Analysis of Anion Radical Excited States","authors":"Naresh Duvva,&nbsp;Tanjila Islam,&nbsp;Silvano R. Valandro,&nbsp;Habtom B. Gobeze,&nbsp;Abul Mansur Muhammed Fahim,&nbsp;Xiaodan Wang,&nbsp;Trang Le,&nbsp;Aimée L. Tomlinson* and Kirk S. Schanze*,&nbsp;","doi":"10.1021/acscentsci.6c00092","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00092","url":null,"abstract":"<p >Excited-state ion radicals have recently attracted attention as powerful reductants or oxidants for electron-transfer photocatalysis. A key challenge in their application as photocatalysts is the short lifetime of their excited states, which directly impacts the efficiency of bimolecular photoinduced electron transfer. Here, we present a comprehensive photophysical study aimed at elucidating the factors that govern the lifetime of the doublet excited state in a series of 10 anion radicals derived from structurally related π-conjugated donor–acceptor–donor (DAD) molecules. In these systems, the acceptor is a 2,1,3-benzothiadiazole (BTD) unit flanked by arylene or oligo(arylene) groups. The anion radicals, generated by chemical reduction in deoxygenated DMF, are stable and were characterized using UV–visible–near-IR absorption/emission spectroscopy and femtosecond transient absorption spectroscopy. Remarkably, the doublet excited state lifetimes vary by nearly 200-fold across the series, ranging from 2.9 to 565 ps. Nonradiative decay rates increase as the excited-state energy decreases, in a manner that is quantitatively consistent with the energy gap law for nonradiative decay. Faster decay is observed for anion radicals with highly delocalized π-systems, reflecting their lower excited-state energies. Finally, we demonstrate the catalytic utility of DAD anion radicals with long-lived doublet excited states in a consecutive photoinduced electron transfer (ConPET) process, using the photodebromination of 4-bromoacetophenone as a model reaction.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"856–866"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299682","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":"Validation of De Novo Designs of Solid-Binding Peptides","authors":"Michael T. Bergman,&nbsp;Fiona Mukherjee,&nbsp;Yufan Feng,&nbsp;Carol K. Hall* and Nicholas L. Abbott*,&nbsp;","doi":"10.1021/acscentsci.5c02193","DOIUrl":"https://doi.org/10.1021/acscentsci.5c02193","url":null,"abstract":"<p >Solid-binding peptides (SBPs) are versatile molecules that can control a range of atomic-scale interfacial processes, but they remain challenging to discover. Current approaches for discovery rely on directed evolution, which samples only a small fraction of possible sequences. Data-driven methods for therapeutic peptides are also not applicable as they rely on crystal structures whereas peptides adopt varied conformations at solid surfaces. To address this challenge, we recently combined biophysical modeling and machine learning to design plastic-binding peptides that were predicted to have strong adsorption enthalpies. Here, we evaluate these designs using steered molecular dynamics and single-molecule force measurements and identify <i>de novo</i> designed peptides that bind strongly to polyethylene. Experimental adhesion forces exceed those previously reported for SBPs, and adsorption free energies from metadynamics simulations support strong binding. Analysis of the designed peptides reveals blocks of non-polar and charged residues, which enables them to adopt conformations that segregate non-polar amino acids to the plastic surfaces (generating hydrophobic interactions) and charged amino acids away from the surfaces. The contact patterns within the non-polar blocks depend on sequence context and polyolefin type. Overall, we validate a general approach for <i>de novo</i> SBP discovery that has broad scientific and engineering applications.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"789–806"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c02193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299735","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":"Local Energy Decomposition of Intramolecular Interactions: The CovaLED Approach and Its Application to Molecular Recognition in Biomolecular Assemblies","authors":"Martina Colucci,&nbsp;Christoph Riplinger,&nbsp;Ahmet Altun,&nbsp;Frank Neese and Giovanni Bistoni*,&nbsp;","doi":"10.1021/acscentsci.6c00336","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00336","url":null,"abstract":"<p >Achieving quantitative insight into the noncovalent interactions that govern molecular function and biological activity in complex assemblies remains a major challenge for quantum chemical analysis, particularly in systems such as nucleic acids where standard force-fields are known to struggle. Local energy decomposition (LED) provides gold-standard coupled-cluster descriptions of intermolecular interactions but can become difficult to interpret chemically when interacting fragments are covalently connected, such as ligands embedded in nucleic acid frameworks or functional groups linked through bonding networks. In these situations, shared electron density across fragment boundaries obscures the physical interpretation of energy contributions. Here we introduce CovaLED, an extension of the LED scheme that enables a rigorous treatment of covalent connectivity within the LED framework. Application to nucleic-acid-based recognition systems demonstrates the capabilities of the approach. In a riboswitch RNA–ligand complex, CovaLED reveals how methylation of guanine leads to a loss of stabilizing hydrogen-bonding interactions, consistent with experimental binding affinity trends. In a segment of human DNA, the method enables accurate quantification of interactions between nucleotides covalently linked within the backbone. CovaLED thus enables coupled-cluster-level energy decomposition in realistic biomolecular systems, where covalent structure and noncovalent recognition are intrinsically intertwined.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"847–855"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299725","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":"Interrupted Reactions in the Synthesis of Subrubine Alkaloids","authors":"Jelena Golijanin,&nbsp;Logan R. Fagu and Andrei K. Yudin​,&nbsp;","doi":"10.1021/acscentsci.6c00767","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00767","url":null,"abstract":"<p >Efficient bio- and chemical total syntheses of subrubine alkaloids are achieved using interrupted construction of the diaza[3.3.3]propellane core.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"741–743"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00767","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299727","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":"Charge-Assisted Hydrogen-Bonding Enables Quantitative Multicomponent Self-Assembly in Strongly Polar Environments","authors":"Beatriz Torres-Calvo,&nbsp;Alberto de Juan,&nbsp;Isabel López-Martín,&nbsp;Miguel García-Iglesias and David González-Rodríguez*,&nbsp;","doi":"10.1021/acscentsci.6c00472","DOIUrl":"https://doi.org/10.1021/acscentsci.6c00472","url":null,"abstract":"<p >Multicomponent discrete assemblies, composed of a defined number of molecular building blocks, represent valuable supramolecular constructs with broad functional potential. Their formation relies on cooperativity, on one hand, and on directional noncovalent interactions, on the other. Many of these interactions have a marked electrostatic component, like H-bonding, and cannot survive in strongly competing polar solvents. A notable exception is the coordination bond, which offers enough strength and selectivity to enable assembly in such polar environments. In this work, we introduce a unique, versatile alternative based on amidinium–carboxylate salt bridges. Concretely, a [2+4] hexacomponent assembly, comprising 2 cofacial tetracarboxylate porphyrins linked through 4 diamidine spacers that exhibits remarkably high kinetic and thermodynamic stability is quantitatively formed in DMSO-rich environments, as a result of the charge-assisted hydrogen-bonding interactions employed and the strong chelate cooperativities attained.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"841–846"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c00472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299730","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":"Synthetic Surrogates of Collagen-Rich Microenvironments: Integrating Modular Bioactive Fibrillar Structure and Tunable Viscoelasticity via Multifunctional Assembling Peptides","authors":"Rafael A. Castro,&nbsp;Lina Pradhan,&nbsp;Jeffrey Caplan,&nbsp;Caitlin D’Ambrosio and April M. Kloxin*,&nbsp;","doi":"10.1021/acscentsci.5c02175","DOIUrl":"https://doi.org/10.1021/acscentsci.5c02175","url":null,"abstract":"<p >Collagen imparts structure, viscoelasticity, and bioactivity to the extracellular matrix (ECM) with variance between organs and between healthy and diseased states. Synthetic mimics of collagen-rich tissues remain a need in applications, from biological studies to regenerative medicine, for parsing and controlling these properties. We designed multifunctional collagen mimetic peptides (mfCMPs) that self-assemble into triple helices and fibrils <i>and</i> contain integrin binding motifs: GFOGER, a binding site within intact collagen I, and RGD, a cryptic binding site available within denatured collagen I. These mfCMPs are incorporated into hydrogel-based synthetic ECMs to impart collagen-like hierarchical structures, viscoelasticity, and bioactivity with modularity. We establish innovative methods for imaging the resulting nano- and micro-structures within the hydrogel using super-resolution microscopy. The physically assembled mfCMPs impart tunable, concentration-dependent viscoelasticity within otherwise elastic, covalently cross-linked hydrogels, exhibiting relaxation half times over orders of magnitude and similar to soft tissues. Notably, breast cancer cells encapsulated and cultured in synthetic ECMs with a bioactive fibrillar structure and viscoelastic properties formed large, growing spheroids. Overall, these modular building blocks provide an innovative tool for creating fully synthetic surrogates of collagen-rich microenvironments, aiding both fundamental and translational biological studies and providing a framework to imbue tunable viscoelasticity to synthetic ECMs.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"12 6","pages":"777–788"},"PeriodicalIF":11.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c02175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148299733","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}