ACS Central Science最新文献

{"title":"Targeted Protein Modification with an Antibody-Based System","authors":"Oded Rimon*,&nbsp;Juraj Konc,&nbsp;Inga Černauskienė,&nbsp;Montader Ali,&nbsp;Vaidehi Roy Chowdhury,&nbsp;Pietro Sormanni,&nbsp;Gonçalo J. L. Bernardes and Michele Vendruscolo*,&nbsp;","doi":"10.1021/acscentsci.5c00651","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00651","url":null,"abstract":"<p >The chemical modification of proteins is one of the major mechanisms used to regulate the properties and functions of these macromolecules in the cell. It is therefore of great interest to develop tools to exploit this type of modification for applications in molecular biology, medicine, and biotechnology. Here we present a method of using antibodies to perform post-translational covalent modifications of endogenous proteins in complex environments by exploiting proximity-driven chemistry. The method is based on the ability of antibodies to hold a weakly reactive group close to its intended site of reaction by binding the target protein on a nearby epitope. We characterize this approach by modifying the green fluorescent protein in increasingly complex environments and illustrate its applicability by targeting the disease-associated protein beta-2 microglobulin.</p><p >An antibody-based system designed to selectively install a post-translational modification on its target achieves robust and selective activity.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1364–1376"},"PeriodicalIF":10.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902064","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":"Identification of Metal–Organic Frameworks for near Practical Energy Limit CO2 Capture from Wet Flue Gases: An Integrated Atomistic and Process Simulation Screening of Experimental MOFs","authors":"Ohmin Kwon,&nbsp;Marco Gibaldi,&nbsp;Kasturi Nagesh Pai,&nbsp;Arvind Rajendran* and Tom K. Woo*,&nbsp;","doi":"10.1021/acscentsci.5c00777","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00777","url":null,"abstract":"<p >Metal–organic framework (MOF) materials have attracted significant attention as solid sorbents for low energy CO₂ capture with adsorption-based gas separation processes. In this work, an integrated screening workflow combining a series of atomistic and process simulations was applied to identify promising MOFs for a 4-step pressure-vacuum swing adsorption (P/VSA) process at three different CO₂ flue gas compositions (6%, 15% and 35%). Starting from 55,818 unique experimentally characterized MOFs, ∼19k porous MOFs were investigated via atomistic grand canonical Monte Carlo (GCMC) simulations and machine learning model-based process optimizations to accelerate the screening of a large candidate database. Thousands of MOFs were identified for each of the CO₂ compositions tested that could achieve within 4% of the practical energy limit of dry CO₂ capture for the P/VSA process while still meeting the 95% CO₂ purity and 90% recovery constraints. From this pool, 3D MOFs without open metal sites were subjected to the multicomponent (CO₂/N₂/H₂O) GCMC simulations at 40% relative humidity. Based on these simulations, hundreds of MOFs were identified at each CO₂ composition that could retain 90% of their CO₂ capture at this humidity while also adsorbing a minimal amount of water. A geometric analysis of these high performing materials revealed that narrow, straight 1D-channels were a common structural motif for low energy wet flue gas CO₂ capture with P/VSA.</p><p >An integrated screening using molecular and process simulations, followed by calculations of CO₂ retainability in humid conditions, identified hundreds of practical sorbents for CO₂ capture.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1438–1451"},"PeriodicalIF":10.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902066","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":"Bidirectional Modification of a Galbulimima Alkaloid Identifies Selective Opioid Ligands","authors":"Florian Martin Zielke,&nbsp;Stone Woo,&nbsp;Samuel Kasmali,&nbsp;Allison Volf,&nbsp;Vuong Q. Dang,&nbsp;Jake B. Bailey,&nbsp;Milan Gembicky,&nbsp;Laura M. Bohn* and Ryan A. Shenvi*,&nbsp;","doi":"10.1021/acscentsci.5c00573","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00573","url":null,"abstract":"<p >We report a bidirectional diversification and optimization campaign of the newly identified <i>mu</i>- and <i>kappa</i>-opioid receptor antagonist GB18, a naturally occurring <i>Galbulimima</i> alkaloid. First, we find that replacement of the GB18 piperidine with pyridine alters the pharmacology from antagonism to partial agonism, with reduced potency but markedly higher receptor selectivity for <i>kappa-</i> over <i>mu-</i>. Second, we optimize this hit via development of a mutually chemoselective cross-coupling of an alkyl iodide/vinyl triflate pair that leads to a series of low- and sub-nanomolar KOR-selective full agonists, some of which demonstrate bias for G protein activation over β-arrestin2 recruitment. Third, we advance three leads to <i>in vivo</i> (mouse) analysis and demonstrate brain penetrance and behavioral effects. In an open-field activity assay, we demonstrate that by increasing G protein signaling preference, agonists display an increase in exploratory, anxiolytic-like behaviors with no signs of sedation. The brevity and success of this campaign, combined with <i>in vitro</i> and <i>in vivo</i> pharmacology, demonstrate GB18 and its analogs as tractable new opioid scaffolds that allow favorable properties to be dialed in and unwanted properties removed.</p><p >Newly discovered GB opioids can be diversified in two steps by mutually chemoselective attached-ring cross-coupling, yielding a series of high potency, G protein-biased, KOR-selective agonists.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1391–1399"},"PeriodicalIF":10.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902067","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":"Investigation on Reactivity and Selectivity of Electrocatalytic CO2 Reduction in Photochemically Synthesized Ag19 and Alloyed Ag19Cu2 and Ag12Cu7 Nanoclusters","authors":"Yu-Xin Wang,&nbsp;Jijie Li,&nbsp;Fu-Qiang Zhang,&nbsp;Zhikai Qi,&nbsp;Fengwei Zhang and Xian-Ming Zhang*,&nbsp;","doi":"10.1021/acscentsci.5c00784","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00784","url":null,"abstract":"<p >Atomically precise nanoclusters are desirable for understanding the structure–property relationships in the electrocatalytic CO₂ reduction reaction (eCO₂RR), but suitable related models are lacking, especially those of low- or zerovalent noble metal nanoclusters and their alloyed analogues. We first developed a photochemical method toward silver nanocluster Ag₁₉(4-^<i>t</i>BuPhC≡C)₁₄(Dpppe)₃(SbF₆)₃ (<b>Ag</b>_<b>19</b>-<b>2e</b>) and then related copper-doped alloyed nanocluster Ag₁₂Cu₇(4-^<i>t</i>BuPhC≡C)₁₄(Dpppe)₃Cl₃(SbF₆)₂ (<b>Ag</b>_<b>12</b><b>Cu</b>_<b>7</b>-<b>0e</b>). Herein, we present a larger alloyed nanocluster, Ag₁₉Cu₂(4-^<i>t</i>BuPhC≡C)₁₆(Dpppe)₄(SbF₆)₃ (<b>Ag</b>_<b>19</b><b>Cu</b>_<b>2</b>-<b>2e</b>) and investigate the relationship between the structures and the eCO₂RR performance of those related nanoclusters. The UV–vis and mass spectra revealed that <b>Ag</b>_<b>19</b><b>Cu</b>_<b>2</b>-<b>2e</b> forms via light-induced <b>Ag</b>_<b>19</b>-<b>2e</b> generation followed by Cu(II) attachment. eCO₂RR tests showed that <b>Ag</b>_<b>19</b>-<b>2e</b> is the least efficient, while its dicopper alloyed <b>Ag</b>_<b>19</b><b>Cu</b>_<b>2</b><b>-2e</b> favors formate, highlighting the important role of copper doping in regulating Ag cluster catalysis. This conclusion is further confirmed by the good catalytic performance of <b>Ag</b>_<b>12</b><b>Cu</b>_<b>7</b>-<b>0e</b>, which demonstrated the best C₁ product selectivity for both CO and formate. Experimental and theoretical calculations indicate that its excellent catalytic performance is attributed to the removal of Cl ligands, exposing active Ag sites for launching the eCO₂RR process. This work not only demonstrates that copper-doped silver nanoclusters significantly enhance catalytic activity but also reveals that varying copper doping levels enable modulation of product selectivity in eCO₂RR.</p><p >This study establishes three structurally related nanocluster catalytic models and reveals that Cu-doping level significantly influences the eCO₂RR product selectivity of Ag nanoclusters.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1428–1437"},"PeriodicalIF":10.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902059","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":"Future Trends in Asymmetric Organo-Metal Combined Catalysis","authors":"Dian-Feng Chen,&nbsp;Jin Song and Liu-Zhu Gong*,&nbsp;","doi":"10.1021/acscentsci.5c00393","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00393","url":null,"abstract":"<p >Asymmetric organo-metal combined catalysis, which integrates the catalytic functions of chiral organocatalysts and metal complexes, enables the enantioselective formation of challenging chemical bonds and facilitates cascade transformations, often without the need for intermediate purification. Since its inception in 2001, this paradigm has evolved into a versatile strategy for the rapid construction of molecular complexity with a high level of enantioselectivity. In this Outlook, we have highlighted the most recent contributions to this field, showcasing exciting opportunities to overcome current efficiency limits. Looking ahead, we foresee the continued evolution of asymmetric organo-metal catalysis, particularly through the exploration of new catalyst scaffolds, the incorporation of external stimuli, the use of heterogeneous metal catalysts, and the application in macromolecular synthesis.</p><p >Asymmetric organo-metal combined catalysis has emerged as a versatile platform for enantioselective synthesis. This Outlook reviews the most recent contributions and foresees opportunities to pursue.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1275–1288"},"PeriodicalIF":10.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00393","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902057","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":"Targeting Sialidase to PD1 Enhances T cell Function and Tumor Control","authors":"Brett M. Garabedian,&nbsp;Eleanor E. Bashian,&nbsp;Xiaoshuang Wang,&nbsp;Andrew J. Thompson and James C. Paulson*,&nbsp;","doi":"10.1021/acscentsci.5c00510","DOIUrl":"https://doi.org/10.1021/acscentsci.5c00510","url":null,"abstract":"<p >Immune therapies targeting the PD1 axis have transformed outcomes in cancer treatment by enhancing T cell-mediated immune responses. However, many tumors evade immune clearance through orthogonal escape mechanisms. Excessive production of immunosuppressive sialic acid-containing glycans (sialoglycans) can impair immune surveillance by recruiting inhibitory Siglecs to the immune synapse where, like PD1, they act as checkpoints for cell activation. Sialic acids can also impact T cell activation by dampening the ligation of the costimulatory receptor CD28 with its ligands. This polypharmacology implicates sialoglycans as a linchpin of tumor immunity that can be targeted to further improve outcomes of PD1 therapies. In this work we conjugated sialidase to anti-PD1 (αPD1-S) to selectively degrade sialic acids on immune cells expressing PD1. Glycan profiling confirmed targeted desialylation, and functional assays demonstrated enhancements to T cell activation and cytotoxic capacity. In a melanoma model, αPD1-S promoted inflammatory macrophage polarization and reduced T cell exhaustion, collectively restricting melanoma growth beyond anti-PD1 (αPD1) alone. By simultaneously blocking PD1 and degrading sialoglycans, αPD1-S provides a novel strategy to enhance T cell-mediated immune responses and improve tumor control in refractory cancers.</p><p >Sialidase conjugated to anti-PD1 degrades inhibitory sialoglycans from PD1+ T cells and tumor cells, enhancing T cell activation and tumor control beyond PD1 blockade alone in refractory cancers.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1417–1427"},"PeriodicalIF":10.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902058","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":"Supramolecular Chiral Assembly Films with Dynamic Handedness and Emitting-Color Afterglow","authors":"Xinkun Ma,&nbsp;Wei Yuan,&nbsp;Wangjian Fang,&nbsp;Letian Chen,&nbsp;Zujin Zhao* and Yanli Zhao*,&nbsp;","doi":"10.1021/acscentsci.5c00847","DOIUrl":"10.1021/acscentsci.5c00847","url":null,"abstract":"<p >This work presents a strategy for the fabrication of multicolor-emitting circularly polarized afterglow (CPA) films by assembling achiral phosphorescent donors and fluorescent emitters in a photonic crystal matrix. Achiral positively charged phosphors and fluorophores with good spectral overlap are selected as the donor and sequential receptors, which are then coassembled with poly(vinyl alcohol) and cellulose nanocrystals. CPA can be achieved in the blue to near-infrared (NIR) range with stepwise amplification of the dissymmetry factor (lifetime up to 4.52 s and dissymmetry factor up to −0.038) through synergistic chirality and energy transfer processes. Notably, the handedness of the CPA signal can be amplified or reversed by altering the receptor types or the direction of incident light. With the flexibility in manipulating emission and handedness, these materials show potential applications in multidimensional anticounterfeiting and high-definition noctilucent displays.</p><p >Supramolecular assembly with chiral cellulose nanocrystal template and Förster resonance energy transfer cascade enables direction-switchable circularly polarized afterglow and NIR emission.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1230–1239"},"PeriodicalIF":10.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725833","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":"Is There More to Magic Mushrooms than Psilocybin?","authors":"Mara Johnson-Groh,&nbsp;","doi":"10.1021/acscentsci.5c01146","DOIUrl":"https://doi.org/10.1021/acscentsci.5c01146","url":null,"abstract":"<p >Some scientists think that including secondary compounds from psychedelic mushrooms can make for better drugs. With scarce data, others remain skeptical.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 8","pages":"1256–1260"},"PeriodicalIF":10.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c01146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902055","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":"Chemistries Moonshot: An Entirely Recyclable Car","authors":"Robin Schoemaker,&nbsp;Chunning Sun,&nbsp;Davide Chiarugi,&nbsp;Theodore Tyrikos-Ergas* and Peter H. Seeberger*,&nbsp;","doi":"10.1021/acscentsci.5c00589","DOIUrl":"10.1021/acscentsci.5c00589","url":null,"abstract":"<p >Automobiles depend on fossil resources – both to create the device and to power it. The automotive industry has decreased this dependency on fossil fuels by developing more fuel-efficient combustion engines, lightweight designs, and biofuels. The rise of battery electric vehicles (BEVs) offers the chance to reduce the fossil footprint by avoiding fuel combustion and exhaust emission. Disruptive approaches toward a truly sustainable car are far from being market-ready. To reach a completely sustainable car, the automotive industry must address the carbon footprint of material production, which is based in the chemical sector. The automotive and chemical industries have to adopt closed-loop thinking, utilize renewable resources for biodegradables, as well as develop novel materials and designs for efficient recycling. Disruptive approaches can arise from predictive models that can accelerate chemical research and enable the discovery of sustainable materials with desirable recycling properties. Integrating generative artificial intelligence (AI) with high-throughput experimental validation will shorten material development cycles and advance the transition to more sustainable products. Moving toward a fully recyclable car is aligning research and development efforts from the chemical sector to the automotive industry and beyond, presenting a giant leap toward a circular economy.</p><p >An outlook on sustainability in the auto industry, focusing on data-driven chemistry to reduce fossil dependency and enable a transition toward a circular economy.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1052–1061"},"PeriodicalIF":10.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725799","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":"Nanoparticles with Ampholytic Surfaces for Binding and Disintegration of Amyloid Fibrils","authors":"Suman Mandal,&nbsp;Minh Dang Nguyen,&nbsp;Nikhil Ranjan Jana* and T. Randall Lee*,&nbsp;","doi":"10.1021/acscentsci.5c00519","DOIUrl":"10.1021/acscentsci.5c00519","url":null,"abstract":"<p >Amyloid fibrils and associated protein aggregates are key contributors to a range of neurodegenerative diseases. Recent studies suggest that nanoparticles with tailored surface chemistries can effectively bind to and disrupt these fibrils. Here, we investigate the role of nanoparticle surface charge in mediating interactions with amyloid fibrils and promoting their disintegration. We synthesized seven types of charged iron oxide nanoparticles (cationic, anionic, and ampholytic) in colloidal form with hydrodynamic diameters ranging from 15 to 40 nm. Interaction studies with mature lysozyme fibrils revealed that ampholytic nanoparticles exhibited the highest binding affinity among the tested surface types. This enhanced affinity is attributed to reduced nonspecific interactions and favorable electrostatic compatibility. Ampholytic nanoparticles disrupted mature amyloid fibrils approximately 2.5 times more effectively than other surface-charged nanoparticles, leading to smaller fibril fragments via mechanical agitation. We further show that agitation-induced mechanical force, along with piezocatalytically generated reactive oxygen species (ROS), contributes to fibril degradation. These findings highlight the critical role of ampholytic surface charge in promoting fibril disintegration and suggest that such nanoparticles could be leveraged in therapeutic strategies for neurodegenerative diseases involving amyloid aggregation.</p><p >Ampholytic nanoparticles bind and disintegrate amyloid fibrils efficiently via electrostatic interactions and ROS generation under agitation; cationic and anionic types are less effective.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 7","pages":"1218–1229"},"PeriodicalIF":10.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725826","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}