ACS Central Science最新文献

{"title":"A Multicomponent Reaction-Based Platform Opens New Avenues in Aryl Hydrocarbon Receptor Modulation","authors":"Pau Nadal Rodríguez,&nbsp;Frederick Hartung,&nbsp;Marina Pedrola,&nbsp;Seemon Coomar,&nbsp;Alejandro Diaz-Moreno,&nbsp;Anna M. Hätälä,&nbsp;Katharina M. Rolfes,&nbsp;Ismael Sánchez-Vera,&nbsp;Joan Gil,&nbsp;Elies Molins,&nbsp;Antonio Viayna,&nbsp;Alexander Hanzl,&nbsp;Nicolas H. Thomä,&nbsp;Thomas Haarmann-Stemmann*,&nbsp;F. Javier Luque*,&nbsp;Rodolfo Lavilla* and Ouldouz Ghashghaei*,&nbsp;","doi":"10.1021/acscentsci.5c0019410.1021/acscentsci.5c00194","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00194https://doi.org/10.1021/acscentsci.5c00194","url":null,"abstract":"<p >A multidisciplinary platform is presented to address aryl hydrocarbon receptor (AhR) modulation. A rewired Yonemitsu multicomponent reaction with indole 2-carboxaldehydes and nucleophilic species was designed to access a family of 6-substituted indolocarbazoles. The conformational behavior of these compounds was examined to rationalize their axial chirality. <i>In silico</i> docking and molecular simulations highlighted key features implicated in their binding to AhR. Furthermore, the synthesis of linkable derivatives allowed the direct development of conjugated entities. Reporter gene and target gene expression analyses identified these novel structures as potent noncytotoxic activating AhR ligands, that can be extended to bifunctional molecules. The anti-inflammatory properties of these AhR agonists were assessed in interleukin-13 treated keratinocytes. Altogether, the synergistic research in synthetic and computational chemistry integrated with biological studies opens novel avenues toward understanding the biological roles of AhR and the development of targeted therapeutics.</p><p >A multicomponent reaction platform yields 6-substituted indolocarbazoles as potent, safe, and modular activators of the Aryl hydrocarbon Receptor (AhR), opening new avenues in AhR research.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"629–641 629–641"},"PeriodicalIF":12.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858524","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 Conversation with Sambuddha Misra","authors":"Payal Dhar,&nbsp;","doi":"10.1021/acscentsci.5c0055710.1021/acscentsci.5c00557","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00557https://doi.org/10.1021/acscentsci.5c00557","url":null,"abstract":"<p >The oceanographer found that lead levels doubled in the western Indian Ocean between 1989 and 2013.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"498–499 498–499"},"PeriodicalIF":12.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858607","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":"Electric-Field Molecular Fingerprinting to Probe Cancer","authors":"Kosmas V. Kepesidis,&nbsp;Philip Jacob,&nbsp;Wolfgang Schweinberger,&nbsp;Marinus Huber,&nbsp;Nico Feiler,&nbsp;Frank Fleischmann,&nbsp;Michael Trubetskov,&nbsp;Liudmila Voronina,&nbsp;Jacqueline Aschauer,&nbsp;Tarek Eissa,&nbsp;Lea Gigou,&nbsp;Patrik Karandušovsky,&nbsp;Ioachim Pupeza,&nbsp;Alexander Weigel,&nbsp;Abdallah Azzeer,&nbsp;Christian G. Stief,&nbsp;Michael Chaloupka,&nbsp;Niels Reinmuth,&nbsp;Jürgen Behr,&nbsp;Thomas Kolben,&nbsp;Nadia Harbeck,&nbsp;Maximilian Reiser,&nbsp;Ferenc Krausz and Mihaela Žigman*,&nbsp;","doi":"10.1021/acscentsci.4c0216410.1021/acscentsci.4c02164","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02164https://doi.org/10.1021/acscentsci.4c02164","url":null,"abstract":"<p >Human biofluids serve as indicators of various physiological states, and recent advances in molecular profiling technologies hold great potential for enhancing clinical diagnostics. Leveraging recent developments in laser-based electric-field molecular fingerprinting, we assess its potential for <i>in vitro</i> diagnostics. In a proof-of-concept clinical study involving 2533 participants, we conducted randomized measurement campaigns to spectroscopically profile bulk venous blood plasma across lung, prostate, breast, and bladder cancer. Employing machine learning, we detected infrared signatures specific to therapy-naı̈ve cancer states, distinguishing them from matched control individuals with a cross-validation ROC AUC of 0.88 for lung cancer and values ranging from 0.68 to 0.69 for the other three cancer entities. In an independent held-out test data set, designed to reflect different experimental conditions from those used during model training, we achieved a lung cancer detection ROC AUC of 0.81. Our study demonstrates that electric-field molecular fingerprinting is a robust technological framework broadly applicable to disease phenotyping under real-world conditions.</p><p >Laser-based infrared molecular fingerprinting detects cancer, demonstrating its potential for clinical disease diagnostics.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"560–573 560–573"},"PeriodicalIF":12.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858519","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":"Detecting the Feeble Electromagnetic Emissions from Cancer Biomarkers","authors":"Marcos Dantus​,&nbsp;","doi":"10.1021/acscentsci.5c0055610.1021/acscentsci.5c00556","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00556https://doi.org/10.1021/acscentsci.5c00556","url":null,"abstract":"<p >Zigman and colleagues use electric-field molecular fingerprinting and machine learning on blood plasma to detect and differentiate major cancers with high precision.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"505–507 505–507"},"PeriodicalIF":12.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00556","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858608","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":"Oceanographers Comb Waters for Genetic Warnings of a Coastal Neurotoxin","authors":"Jonathan Feakins,&nbsp;","doi":"10.1021/acscentsci.5c0055810.1021/acscentsci.5c00558","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00558https://doi.org/10.1021/acscentsci.5c00558","url":null,"abstract":"<p >To catch toxic algal blooms before they take over ecosystems, researchers are analyzing the vast body of environmental DNA, loose genetic material, in the ocean.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"500–504 500–504"},"PeriodicalIF":12.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858703","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":"Where Molecules Meet Mucus: Mutanofactins in the Oral Microbiome","authors":"McKenna Loop Yao,&nbsp; and ,&nbsp;Wenjun Zhang​​,&nbsp;","doi":"10.1021/acscentsci.5c0054610.1021/acscentsci.5c00546","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00546https://doi.org/10.1021/acscentsci.5c00546","url":null,"abstract":"<p >Fully synthesized mutanofactins modulate biofilms in select oral species and alter mucins, revealing broader roles for oral specialized metabolism.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"508–510 508–510"},"PeriodicalIF":12.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858395","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 Source of the Mysterious m/z 36 Ions Identified: Implications for the Stability of Water and Unusual Chemistry in Microdroplets","authors":"Casey J. Chen,&nbsp; and ,&nbsp;Evan R. Williams*,&nbsp;","doi":"10.1021/acscentsci.5c0030610.1021/acscentsci.5c00306","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00306https://doi.org/10.1021/acscentsci.5c00306","url":null,"abstract":"<p >Many unusual reactions involving aqueous microdroplets have been reported, including nitrogen fixation at room temperature, production of abundant hydrogen peroxide, and formation of an ion at <i>m/z</i> 36, attributed to (H₂O–OH₂)^+•, (H₃O + OH)^+•, or (H₂O)₂^+•, which was used to support the hypothesis of spontaneous production of hydroxyl radicals. Here, <i>m</i>/<i>z</i> 36 ions and extensive hydrated clusters of this ion are formed using either nanoelectrospray ionization or a vibrating mesh nebulizer that produces water droplets ranging from ∼100 nm to ∼20 μm. Exhalation of a single breath near the droplets leads to a substantial increase in the abundance of this ion series, whereas purging the source with N₂ gas leads to its near complete disappearance. Accurate mass measurements show that <i>m</i>/z 36 ions formed from pure water are NH₄⁺(H₂O) and not (H₂O)₂^+•. Both the high sensitivity to trace levels of gaseous ammonia (unoptimized detection limit of low parts-per-billion) in these experiments and the likely misidentification of the <i>m</i>/<i>z</i> 36 ion in many previous experiments indicate that many results that have been used to support hypotheses about unusual chemistry and the effects of high intrinsic electric fields at microdroplet surfaces may require a more thorough evaluation.</p><p >Accurate mass measurements show that a <i>m</i>/<i>z</i> 36 ion that is sometimes formed from aqueous microdroplets is NH₄⁺(H₂O), not (H₂O)₂^+•, and is abundant when droplets are exposed to human breath.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"622–628 622–628"},"PeriodicalIF":12.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.5c00306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858394","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":"Leveraging Prompt Engineering in Large Language Models for Accelerating Chemical Research","authors":"Feifei Luo,&nbsp;Jinglang Zhang,&nbsp;Qilong Wang* and Chunpeng Yang*,&nbsp;","doi":"10.1021/acscentsci.4c0193510.1021/acscentsci.4c01935","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01935https://doi.org/10.1021/acscentsci.4c01935","url":null,"abstract":"<p >Artificial intelligence (AI) using large language models (LLMs) such as GPTs has revolutionized various fields. Recently, LLMs have also made inroads in chemical research even for users without expertise in coding. However, applying LLMs directly may lead to “hallucinations”, where the model generates unreliable or inaccurate information and is further exacerbated by limited data set and inherent complexity of chemical reports. To counteract this, researchers have suggested prompt engineering, which can convey human ideas formatively and unambiguously to LLMs and simultaneously improve LLMs’ reasoning capability. So far, prompt engineering remains underutilized in chemistry, with many chemists barely acquainted with its principle and techniques. In this Outlook, we delve into various prompt engineering techniques and illustrate relevant examples for extensive research from metal–organic frameworks and fast-charging batteries to autonomous experiments. We also elucidate the current limitations of prompt engineering with LLMs such as incomplete or biased outcomes and constraints imposed by closed-source limitations. Although LLM-assisted chemical research is still in its early stages, the application of prompt engineering will significantly enhance accuracy and reliability, thereby accelerating chemical research.</p><p >AI using large language models creates an unprecedented opportunity for chemical discovery and prompt engineering hopefully unleashes their true potential for accelerating chemical research.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"511–519 511–519"},"PeriodicalIF":12.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858351","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":"Amino Acid Sequence Controls Enhanced Electron Transport in Heme-Binding Peptide Monolayers","authors":"Hao Yang,&nbsp;Xiaolin Liu,&nbsp;Moeen Meigooni,&nbsp;Li Zhang,&nbsp;Jitong Ren,&nbsp;Qian Chen,&nbsp;Mark Losego,&nbsp;Emad Tajkhorshid*,&nbsp;Jeffrey S. Moore* and Charles M. Schroeder*,&nbsp;","doi":"10.1021/acscentsci.4c0184910.1021/acscentsci.4c01849","DOIUrl":"https://doi.org/10.1021/acscentsci.4c01849https://doi.org/10.1021/acscentsci.4c01849","url":null,"abstract":"<p >Metal-binding proteins have the exceptional ability to facilitate long-range electron transport in nature. Despite recent progress, the sequence-structure–function relationships governing electron transport in heme-binding peptides and protein assemblies are not yet fully understood. In this work, the electronic properties of a series of heme-binding peptides inspired by cytochrome <i>bc</i>₁ are studied using a combination of molecular electronics experiments, molecular modeling, and simulation. Self-assembled monolayers (SAMs) are prepared using sequence-defined heme-binding peptides capable of forming helical secondary structures. Following monolayer formation, the structural properties and chemical composition of assembled peptides are determined using atomic force microscopy and X-ray photoelectron spectroscopy, and the electronic properties (current density–voltage response) are characterized using a soft contact liquid metal electrode method based on eutectic gallium–indium alloys (EGaIn). Our results show a substantial 1000-fold increase in current density across SAM junctions upon addition of heme compared to identical peptide sequences in the absence of heme, while maintaining a constant junction thickness. These findings show that amino acid composition and sequence directly control enhancements in electron transport in heme-binding peptides. Overall, this study demonstrates the potential of using sequence-defined synthetic peptides inspired by nature as functional bioelectronic materials.</p><p >Self-assembled peptide monolayers show a 1000-fold increase in electronic conductivity upon heme binding, demonstrating that electronic properties in bioelectronic materials can be tuned by controlling peptide sequence and composition.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"612–621 612–621"},"PeriodicalIF":12.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c01849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858349","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":"Synthesis, Microbiology, and Biophysical Characterization of Mutanofactins from the Human Oral Microbiome","authors":"Lukas Lüthy,&nbsp;Leon Gabor Sacha Thies,&nbsp;Konstantin Nikolaus Beitl,&nbsp;Moritz Hansen,&nbsp;Joshua McManus,&nbsp;Muhammad Afzal,&nbsp;Lukas Schrangl,&nbsp;Susanne Bloch,&nbsp;Guruprakash Subbiahdoss,&nbsp;Erik Reimhult*,&nbsp;Christina Schäffer* and Erick M. Carreira*,&nbsp;","doi":"10.1021/acscentsci.4c0218410.1021/acscentsci.4c02184","DOIUrl":"https://doi.org/10.1021/acscentsci.4c02184https://doi.org/10.1021/acscentsci.4c02184","url":null,"abstract":"<p >Mutanofactins are a family of natural products produced by <i>Streptococcus mutans</i> from the human oral microbiome. We report a unified approach to all mutanofactins by developing a total synthesis amenable to diversification. The key to success for the most complex members, mutanofactins 607 and 697, was an acyl ketene based strategy. Access to the family enabled comprehensive biological profiling, where we demonstrate that all mutanofactins are biofilm promoting in <i>Streptococcus mutans</i>. Experiments were extended to other inhabitants of the oral microbiome for the first time: <i>Streptococcus gordonii</i> and <i>Streptococcus oralis</i>, two early colonizers, were similarly affected with mutanofactins being biofilm promoting. Conversely, <i>Veillonella dispar</i> and <i>Fusobacterium nucleatum</i> showed little to no reaction to mutanofactins. Biophysical investigations based on quartz crystal microbalance with dissipation monitoring and atomic force microscopy reveal a previously unknown mucin–mutanofactin 697 interaction. Incubation of a mucin layer with mutanofactin 697 induces a morphology change within the mucin layer, which promotes bacterial adhesion and biofilm formation. This unique property of mutanofactin 697 might be key to early stages of biofilm formation in the human oral microbiome. Combined, an interdisciplinary approach consisting of total synthesis, microbiology and biophysical characterization provides insight into the roles of mutanofactins in the oral microbiome.</p><p >Mutanofactins are metabolites from the human oral microbiome. Our study includes synthesis, microbiology and biophysics. Key results are effects on mucin and biofilms of commensal bacteria.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 4","pages":"601–611 601–611"},"PeriodicalIF":12.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.4c02184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858425","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}