Chemical Science最新文献

{"title":"Molecular Engineering of CRISPR/Cas12a: From Activity Enhancement to Exponential Signal Amplification","authors":"Qing-Nan Li, Qi-Fan Yang, Wei-Liang jin, Xiaozhe Pang, Wen-Bo Sun, Jia Xin Wang, Xin Yue Wang, An-na Tang, Deming Kong, Li-Na Zhu","doi":"10.1039/d6sc02276f","DOIUrl":"https://doi.org/10.1039/d6sc02276f","url":null,"abstract":"CRISPR/Cas12a has emerged as a powerful tool for molecular diagnostics, yet its inherent linear signal output and limited amplification efficiency constrain its detection sensitivity. Conventional approaches that rely on coupling with pre-amplification techniques increase operational complexity and introduce potential uncertainties, thereby hindering clinical translation. This review highlights a paradigm shift: moving beyond the canonical \"one-target–one-enzyme\" model through molecular engineering to intrinsically enhance the catalytic activity of CRISPR/Cas12a and even achieve exponential signal amplification. We systematically summarize key strategies, including crRNA reprogramming, activator strand engineering, reporter probe design, and reaction environment optimization, that collectively enhance Cas12a’s kinetics, specificity, and intrinsic signal gain. These integrated engineering approaches enable ultrasensitive, pre-amplification-free detection of both nucleic acids and non-nucleic acid targets, paving the way for the next generation of robust and field-deployable point-of-care diagnostics.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"2 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751630","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}

{"title":"How Fluorine Substituents Strengthen Aryl C-H Bonds","authors":"Daniel Arley Santos Oliveira, Daniela Rodrigues Silva, Ataualpa A. C. Braga, Célia Fonseca Guerra, Robin Perutz, Odile Eisenstein, F. Matthias Bickelhaupt","doi":"10.1039/d6sc01846g","DOIUrl":"https://doi.org/10.1039/d6sc01846g","url":null,"abstract":"We have investigated the nature and bond dissociation energies (BDEs) of the aromatic C–H bonds in fluorinated benzenes C6R5H (each R can be H or F) using quantitative Kohn-Sham molecular orbital theory and a matching energy decomposition analysis (EDA). The C–H bond becomes stronger as the number of fluorine atoms in the benzene ring increases. This increase in the calculated BDE is additive and most pronounced for ortho-substituted C–H bonds. Our analyses of the C–H bond between C6R5• and H• reveal that a fluorine inductive effect is responsible for this. Fluorine polarizes the closed-shell molecular orbitals of C6R5• away from the carbon radical center and in this way reduces Pauli repulsion between [C•] and the H• radical, leading to a stronger C–H bond. The ortho effect can be accurately modelled by a combination of Pauli repulsion (main contribution) and orbital interactions. We extend our analysis to other substituents, including ones with the opposite effect on C–H bond strength.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"18 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753519","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}

{"title":"Direct Visualization of Inner-Sphere Electrocatalytic Reactions as They Occur at Detachable Electrochemical Interfaces","authors":"Xiangbiao Zeng, Peimeng Qiu, Xi Cui, Chengbiao Zhu, Chen Zeng, Jianxiong Chen, Peng Li, Shengli Chen, Zhenwei Wei","doi":"10.1039/d6sc01821a","DOIUrl":"https://doi.org/10.1039/d6sc01821a","url":null,"abstract":"Molecular-level observation of inner-sphere electrocatalytic reaction has remained a longstanding challenge. Although recent advances in in situ and operando mass spectrometry enable probing of complex electrochemical processes, intrinsic limitations of mass spectrometry hinder characterization of adsorbed intermediates at inner-sphere interfaces.Here, we report a detachable electrochemical interface strategy that enables direct visualization of inner-sphere electrocatalytic reactions as they occur. A positively charged [Au9(PPh3)8]3+ nanocluster acts as a molecular interfacial carrier that selectively assembles at the cathodic interface and mediates electron transfer.Under reaction potentials, changes in the charges of the cluster weaken its interaction with the electrode, allowing reaction information bearing clusters to desorb into solution for immediate mass spectrometric analysis while retaining their interfacial origin. Based on this strategy, we achieve operando visualization of multiple types of inner-sphere electrocatalytic processes. In the hydrogen evolution reaction, we directly observed short-lived hydrogen intermediates on the [Au9(PPh3)8]3+ associated with proton-coupled electron transfer pathways, with the interfacial species identified as [Au9H(PPh3)8]3+. In the reduction of nitrosobenzene, we captured the formation of nitrosobenzene radical anions at the interface ([Au9(PPh3)7 + PhNO]2+) and their evolution pathway in solution phase. Additionally, in the interface reconstruction reaction, we observed the potential-dependent reconstruction and growth of [Au9(PPh3)8]3+ and [Au11(PPh3)8]3+ in the presence of metal ions, providing new insights into interfacial reconstruction phenomena.By converting previously elusive interfacial reactions into directly observable single chemical entities, this work establishes a general operando platform for probing short-lived inner-sphere electrocatalytic intermediates, bridging a critical gap between interfacial reaction chemistry and molecular-level detection.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"28 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751613","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}

{"title":"Light-Driven Radical Catch-and-Release with BODIPY Photocages","authors":"Anna Poryvai, Anna Vasiļevska, Karolína Bangievská, Ján Tarábek, Sandrine Gerber-Lemaire, Tomáš Slanina","doi":"10.1039/d6sc01848c","DOIUrl":"https://doi.org/10.1039/d6sc01848c","url":null,"abstract":"Photocages release payloads upon light irradiation and are widely used for spatiotemporal control in chemical biology and materials science. Although payload release is almost universally described as a heterolytic process, homolytic pathways that generate radicals can interfere and produce unintended off-target effects. If controlled, radical photorelease would open new avenues for applications such as polymerization, however the molecular factors that govern this process in photocages remain unknown. Here, we investigate how photophysics and payload identity influence heterolytic vs homolytic reactivity in BODIPY photocages. We find that high fluorescence quantum yields correlate with efficient homolytic cleavage, enabling reversible radical catch-and-release: light-assisted capture of radical payloads followed by clean photorelease under green light. This radical release can be suppressed by the introduction of iodide or boron-methyl substituents which promote intersystem crossing. We achieve the highest photorelease quantum yield reported to date for green-light-driven radical generation (Φ<small>_r</small> = 0.5%), surpassing heterolytic carboxylate uncaging. We further exploit this reactivity in Type I photoinitiation of RAFT polymerization, yielding fluorescently labelled polymers with defined dispersity. This work establishes a structure–reactivity framework for predictable light-controlled radical generation, enabling mitigation of off-target radical effects and opening new avenues for late-stage photochemical payload installation.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"21 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751610","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}

{"title":"Mechanistic Insights into Azo Compound Back-Isomerization from Spin-Flip Time-Dependent DFT combined to Marcus Theory","authors":"Ari Serez, Flavia Aleotti, Pascal Gerbaux, Luca Muccioli, Jerome Cornil","doi":"10.1039/d6sc01578f","DOIUrl":"https://doi.org/10.1039/d6sc01578f","url":null,"abstract":"Interest in photosensitive molecules has increased significantly over the past decade, with particular attention given to photoswitchable systems. Among these, azobenzene stands out as a reference compound due to its broad range of applications, in particular for solar energy storage. While the trans-to-cis photoisomerization has been relatively well characterized, the reverse cis-to-trans isomerization remains a complex process potentially involving multi-state physics. In this study, we compile recent theoretical advances aimed at modeling this process and introduce, through the spin-flip time-dependent density functional theory (SF-TDDFT) approach combined to the semiclassical Marcus equation, a fast and efficient method to investigate the mechanisms of thermal back-isomerization of azo derivatives. By comparing various exchange-correlation functionals with CASPT2 reference data, we demonstrate that the PBE0(D3BJ) functional provides an accurate description for the non-adiabatic rotational pathway. We successfully reproduce the experimental values (88.6 vs. 88.3 kJ/mol for the experimental enthalpy of activation, and -53.0 vs. -50.2 J/mol • K for the experimental entropy of activation) for azobenzene, thus motivating the extension of this methodology to other azo derivatives. This approach can be further generalized to a broader class of azo-based photo-switches in future studies.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"151 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751612","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}

{"title":"Target-agnostic SAR mapping and immunological evaluation of (−)-FR252921 and analogs against primary human immune cells","authors":"Iakovos Saridakis, Manuel Schupp, Haoqi Zhang, Thomas Leischner, Laura Marie Gail, Konstantin Günther, Martina Drescher, Florian Doubek, Daniel Kaiser, Georg Stary, Nuno Maulide","doi":"10.1039/d5sc09554a","DOIUrl":"https://doi.org/10.1039/d5sc09554a","url":null,"abstract":"The macrocyclic immunosuppressive natural product (−)-FR252921 was isolated in 2003 from a liquid culture of <em>Pseudomonas fluorescens</em>. Despite promising preliminary immunological insights, in-depth studies that advance our understanding of structure–activity relationship (SAR) have been scarce. Herein we document a detailed SAR mapping of (−)-FR252921 by the syntheses of 14 analogs and their subsequent evaluation. The composed library of analogs was designed to address crucial questions regarding the roles of explicit molecular features of the natural product while following a target-agnostic efficacy approach. Whereas previous efforts have focused on murine T cell assays, our endeavors transit to a primary human cell-based immunological platform using peripheral blood mononuclear cells (PBMCs), enabling direct assessment of immunosuppressive activity in B, natural killer (NK), and T cells <em>via</em> cytokine suppression. We emphasize that a new fully synthetic (−)-FR252921 analog (<strong>fs-FR4</strong>) profoundly outperformed the natural product in suppressing the response of both stimulated B cells (21-fold) and NK cells (16-fold) within the context the biological assays used, validating the power of our platform and standing as a lead candidate for further preclinical development. Lastly, we highlight that our studies included significant improvement in the synthetic efficacy of previously reported building blocks and key synthetic steps towards (−)-FR252921 and analogs.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"2018 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147753538","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}

{"title":"Synergistic Decatungstate and Brønsted Acid Catalysis Enables Direct C-H Indolation of Alkanes and Aldehydes","authors":"Gangqi Peng, Yangling Deng, Mengxuan Zhang, Yuxuan He, Hao Cheng, Xinbin Wang, Yuanyuan An, Guanyinsheng Qiu, Danqing Zheng","doi":"10.1039/d6sc01827k","DOIUrl":"https://doi.org/10.1039/d6sc01827k","url":null,"abstract":"Indole skeletons are ubiquitous in natural products, pharmaceuticals, and agricultural agents, making direct C-H indolation strategies highly significant. Direct radical alkylation of indoles, however, is often hampered by the inherent polarity mismatch between nucleophilic alkyl radicals and the electron-rich indole ring. Herein, we report that synergistic decatungstate and Brønsted acid catalysis enables the direct radical C-H indolation of alkanes and aldehydes with 2indolylmethanols. The acid-mediated ionization of 2-indolylmethanols generates delocalized carbocations, which efficiently capture alkyl or acyl radicals derived from the decatungstate-catalyzed hydrogen atom transfer (HAT) process. This cascade delivers C3-functionalized indoles with high regioselectivity under mild conditions. Mechanism studies suggest the Brønsted acid plays a dual role by facilitating the formation of key carbocation intermediates and accelerating the HAT step. The latestage C-H indolation of complex natural products and pharmaceutical agents further demonstrates the synthetic versatility of this protocol.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"8 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147755281","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}

{"title":"Understanding the Precipitation Mechanism in Pentavalent Vanadium Electrolytes through Deep Learning Potential Molecular Dynamics","authors":"Chenkai Mu, Chenbo Zhan, Tianyu Li, Xianfeng Li","doi":"10.1039/d6sc02403c","DOIUrl":"https://doi.org/10.1039/d6sc02403c","url":null,"abstract":"Vanadium flow batteries (VFBs) represent one of the promising options for large-scale energy storage, yet the precipitation of pentavalent (V(V)) species under elevated temperature and high state-of-charge severely limits energy density and cycle life. However, due to the lack of approaches capable of tracking the liquid-to-solid transition at atomic resolution, the mechanism underlying this precipitation has remained elusive. Here, we employ deep potential molecular dynamics (DPMD) to investigate the precipitation process in vanadium electrolytes. A high-accuracy deep potential model, with energy errors below 1 meV and force errors below 60 meV Å−1, was developed through active learning. And complete transformation of V(V) from hydrated species to vanadium oxide precipitates was simulated. The results reveal that precipitation proceeds via hydroxyl dehydration-transformation following an SN2-type pathway with an activation barrier of approximately 40 kJ mol−1. Based on these mechanistic insights, an anion coordination strategy was proposed to suppress precipitation. Experimental validation confirmed that strongly coordinating anions such as phosphate and arsenate extend precipitation onset from 10 hours to 150-200 hours at 50 °C. This study elucidates the precipitation mechanism and provides guidance for electrolyte formulation optimization in vanadium flow batteries.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"9 12 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751614","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}

{"title":"High-Capacity Sieving of C3F6 and C3F8 by a Copper-Based MOF with Interconnected Gourd-Shaped Channels","authors":"Zijian Wang, Mu-Yang Zhou, Shanshan Mao, Yi-Lu Wu, Shenfang Li, Xin Zhou, Fu-An Guo, Liang Yu, Manglai Gao, Hao Wang","doi":"10.1039/d6sc01756h","DOIUrl":"https://doi.org/10.1039/d6sc01756h","url":null,"abstract":"Targeting the challenging purification of electronic-grade C<small>₃</small>F<small>₈</small>, we report the size-sieving separation of C<small>₃</small>F<small>₆</small> and C<small>₃</small>F<small>₈</small> by a robust copper-based metal-organic framework, <strong>CuHTPO</strong>, that features a distinctive interconnected “gourd”-shaped pore architecture. This compound completely excludes C<small>₃</small>F<small>₈</small> while strongly adsorbing C<small>₃</small>F<small>₆</small>, achieving an adsorption capacity as high as 71.3 cm<small>³</small> g<small>^-1</small> at 298 K and 100 kPa. Dynamic breakthrough experiments demonstrate the direct production of ultra-high-purity C<small>₃</small>F<small>₈</small> (&gt;5N) from a C<small>₃</small>F<small>₆</small>/C<small>₃</small>F<small>₈</small> (10:90, v/v) gas mixture. The underlying size-sieving-based separation mechanism is corroborated by in situ infrared spectroscopy and density functional theory calculations.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"33 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147736131","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}

{"title":"White-light powered autonomous molecular ratchet drives PdII capsules out of equilibrium","authors":"Lidón Pruñonosa Lara, Benedikt Bädorf, Maximilian J. Notheis, Gregor Schnakenburg, Stefan Grimme, Larissa K. S. von Krbek","doi":"10.1039/d5sc09472k","DOIUrl":"https://doi.org/10.1039/d5sc09472k","url":null,"abstract":"Using an energy source to drive chemical reactions away from equilibrium is essential for life and remains a significant challenge in designing artificial out-of-equilibrium nanosystems and molecular machines. Achieving autonomous operation of such systems, as observed in nature, presents an even greater difficulty. Here, we report Pd<small>^II</small>-mediated coordination capsules based on ligand <strong>1</strong> embedding an azobispyrazole photoswitch. The more thermodynamically stable Ephotoisomer forms an equilibrium mixture of a Pd<small>^II</small><small>₃</small>(<em>E</em>-<strong>1</strong>)<small>₆</small> double-walled triangle and a Pd<small>^II</small><small>₂</small>(<em>E</em>-<strong>1</strong>)<small>₄</small> lantern in a 78:22 ratio. UV-light irradiation transforms both structures into a Pd<small>^II</small><small>₂</small>(<em>Z</em>-<strong>1</strong>)<small>₄</small> lantern, which then reverts solely to the out-of-equilibrium Pd<small>^II</small><small>₂</small>(<em>E</em>-<strong>1</strong>)<small>₄</small> lantern when exposed to visible light. The complete photoisomerisation proceeds through an information ratchet mechanism that can operate autonomously under continuous white light or sunlight exposure, selectively accumulating the out-of-equilibrium Pd<small>^II</small><small>₂</small>(<em>E</em>-<strong>1</strong>)<small>₄</small> structure. This work demonstrates how autonomous, light-driven processes can be harnessed to direct non-equilibrium behaviour in complex coordination assemblies.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"19 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147736166","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}