Accounts of Chemical Research最新文献

{"title":"Next Generation of CO2-Responsive Materials Constructed by Dynamic Gas-Bridged Chemistry","authors":"Yang-Yang Wang, Qiang Yan","doi":"10.1021/acs.accounts.6c00335","DOIUrl":"10.1021/acs.accounts.6c00335","url":null,"abstract":"<p>Stimuli-responsive materials,which undergoreversible structural/phasetransitions in response to stimuli, represent one of the most activeand appealing research areas in intelligent materials. Compared toother external cues, carbon dioxide (CO<sub>2</sub>) as a unique gaseousstimulus offers distinct advantages, including being green and chemical-waste-freeand offering ease of introduction and removal and spatiotemporal control,and exhibits promising applications in diverse fields such as CO<sub>2</sub> capture and utilization, gas sensors, biomedicines, and smartinterfaces. Despite substantial advancements, conventional CO<sub>2</sub>-responsive systems predominantly rely on a Brønstedacid–base mechanism by which tertiary amine or nitrogen-bearingbasic groups react with hydrated CO<sub>2</sub>. Since this mechanismentails the participation of H<sub>2</sub>O molecules and the generatedcarbonic acid (H<sub>2</sub>CO<sub>3</sub>) is inherently weak andmetastable, the reactive process compromises on slow response rates,short lifetimes, and heavy environmental dependence, which highlyimpede its utility in smart control and functional switching. In thiscontext, the molecular principle behind CO<sub>2</sub>-responsivematerials desires an urgent breakthrough.</p><p>Building on the foundationwork from our research, this Accountpresents a concept of dynamic gas-bridged chemistry (DGB) and leveragesit to realize a second CO<sub>2</sub> response mechanism. This mechanismcan avoid the Brønsted acid–base reaction (CO<sub>2</sub> + H<sub>2</sub>O + R<sub>3</sub>N ⇄ R<sub>3</sub>NH<sup>+</sup> + HCO<sub>3</sub><sup>–</sup>) and involves direct dynamicbinding between CO<sub>2</sub> gas and a triarylborane/triarylphosphine-basedfrustrated Lewis pair (FLP) to form a dative gas-bridging structure(CO<sub>2</sub> + Ar<sub>3</sub>B + Ar<sub>3</sub>P → Ar<sub>3</sub>P–CO<sub>2</sub>–BAr<sub>3</sub>). DGB has twoadvantages: (i) it belongs to a unique class of dynamic covalent bondingthat endows the materials with favorable stability while maintainingreversible dissociation, and (ii) its binding kinetics (10–30s) conquers the limit of response rate in first-generation CO<sub>2</sub>-sensitive materials. In this Account, we first introducethe chemical essence of DGB for replying to CO<sub>2</sub> and highlightits noncanonical properties distinct from common dynamic bonds, called“gas-bridge metathesis” and “gas-bridge semiactivation”,which respectively become the foundation of CO<sub>2</sub>-regulatedself-assembly and CO<sub>2</sub>-involved efficient catalysis. Second,we summarize the advance of a new generation of CO<sub>2</sub>-responsivematerials on the basis of the DGB principle, including how to exploitCO<sub>2</sub> gas as a connector to construct multidimensional materials,use CO<sub>2</sub> as a trigger to manipulate self-assembly kineticsand reshuffle material architectures, and establish CO<sub>2</sub>-involved porous and nanomaterial platforms for high-perform","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2425–2437"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428968","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":"Rational Design of Supramolecular Fe and Mn Oxidation Catalysts","authors":"Giorgio Olivo,&nbsp;Miquel Costas,&nbsp;Stefano Di Stefano","doi":"10.1021/acs.accounts.6c00368","DOIUrl":"10.1021/acs.accounts.6c00368","url":null,"abstract":"<p>Modern organic synthesis aimsto prepare the target molecule ina minimal number of steps. Hence, the efficiency, selectivity, andpredictability of each of these steps need to be carefully optimized,even at a late stage of a synthetic route. This is particularly truein the case of aliphatic C–H functionalization, since differentiatingone C–H bond among many others with similar properties in organicmolecules often stands as an open challenge. Remote, inactivated C–Hsites are especially difficult to target. Supramolecular catalysisrepresents one of the tools to overcome such problems. As occurs inenzymes, substrate binding to a supramolecular catalyst constrainstheir relative orientation, and the resulting preorganization canincrease reactivity and unlock unusual selectivity in a rational andpredictable manner, meeting late-stage functionalization requirements.In fact, supramolecular catalysis, which was initially oriented tothe comprehension of the mechanisms of the involved reactions, iscurrently and rapidly evolving into a synthetically useful tool.</p><p>One decade ago, in 2017, we described Fe- and Mn-based supramolecularcatalysts equipped with crown ether recognition sites able to efficientlycatalyze the oxidation of inactivated C–H bonds in protonatedprimary amines. Substrate preorganization induced by recognition enableselusive oxidation at remote C8 and C9 sites in linear alkyl chains.Since then, a number of follow-up investigations allowed us to rationallyelicit unnatural reactivity and selectivity in different bioinspiredoxidation reactions, including predictable, late-stage C–Hoxidation of steroids. In addition, an in-depth analysis of such oxidationprocesses provides a deep comprehension of the action mechanism ofthese supramolecular catalysts.</p><p>In this Account, we discussthe above investigations aiming toshow (i) the rational approach to the design of a supramolecular oxidationcatalyst, (ii) the experimental and theoretical tools that help understandand assess its mechanism of action, and (iii) its potential to addresssynthetic challenges. Eventually, a section that compares our approachto the one of other research groups illustrates the state of the artin supramolecular oxidation catalysis.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2503–2515"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148539200","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":"Metal–Organic Framework “Molecule-Trap” Adsorbents","authors":"Guang-Rui Si,&nbsp;Lin-Hua Xie,&nbsp;Xin Zhang,&nbsp;Tao He,&nbsp;Xiang-Jing Kong,&nbsp;Jian-Rong Li","doi":"10.1021/acs.accounts.6c00409","DOIUrl":"10.1021/acs.accounts.6c00409","url":null,"abstract":"<p>The development of adsorbentsacting as “moleculetraps”for advanced adsorption and separations on specific molecular recognitionhas garnered increasing attention over the past decade. Molecule trappingcan be understood as strong confinement of guest molecules withinwell-defined local environments inside adsorbents, where adsorptionis governed by geometric matching and multiple host–guest interactionsrather than nonspecific van der Waals interactions alone. This site-specifictrapping strategy enables precise discrimination between moleculeswith similar physicochemical properties under complex separation conditions.In particular, metal–organic frameworks (MOFs) provide an idealplatform for constructing molecule traps because their modular, designable,and crystalline structures enable the precise spatial organizationof binding sites and confined pore environments.</p><p>This Accounthighlights our recent advances in MOF-based molecule-trapadsorbents, from the foundational concept of the single-molecule trapto diverse trapping modes, including aromatic, localized, dynamic,and reactive trapping. These trapping modes enable selective recognitionand capture/separation of hydrocarbons, greenhouse gases, and airpollutants through distinct confined interaction environments. Beyondempirical design, molecule trapping is also increasingly being guidedby data-driven approaches, including large language model-assistedextraction of structure–function relationships and mechanism-basedanalysis. Furthermore, advances in scalable synthesis, material shaping,and continuous operation have moved MOF-based molecule-trap adsorbentscloser to practical separation processes. These studies suggest thatmolecule trapping can serve as a useful design strategy for adsorptionand separation media, providing a conceptual framework for the developmentof next-generation porous materials.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2575–2586"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589169","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":"London Dispersion in Confined Chiral Ion-Pair Asymmetric Catalysis: From Background Interaction to Design Principle","authors":"Lorenzo Baldinelli,&nbsp;Giovanni Bistoni","doi":"10.1021/acs.accounts.6c00299","DOIUrl":"10.1021/acs.accounts.6c00299","url":null,"abstract":"&lt;p&gt;As molecular systems of increasingcomplexity come to dominatethe frontiers of chemistry, biology, and materials science, the temptationgrows to bypass mechanistic understanding in favor of correlations(whether empirical or learned) that capture trends without illuminatingtheir origins. Yet, for systems governed by dense networks of noncovalentinteractions, correlations without causation offer limited transferability.The deeper challenge lies in forging an understanding that is at oncequantitatively rigorous and chemically intuitive: principles rootedin the physics of these interactions, capable of explaining why asystem behaves as it does and of guiding its rational redesign.&lt;/p&gt;&lt;p&gt;We believe that extracting such transferable insights from theaccurate characterization of noncovalent interactions in complex systemsis a central objective of modern computational chemistry. This challengeintensifies as molecular architectures grow in size and flexibility,entering a regime in which the tools of small-molecule quantum chemistryand the sampling demands of biomolecular simulations must converge.Here, we examine an especially challenging case study: harnessingLondon dispersion in confined asymmetric catalysis.&lt;/p&gt;&lt;p&gt;London dispersionis among the most pervasive yet least exploitedforces in asymmetric catalysis. In enzymes, precisely shaped activesites achieve extraordinary selectivity by confining substrates withinpockets rich in noncovalent contacts. Confined chiral catalysts emulatethis strategy: their enclosed active sites shape the conformationalspace of catalyst–substrate assemblies multiplying short-rangecontacts, enhancing a contribution whose role in stereocontrol growswith the degree of confinement.&lt;/p&gt;&lt;p&gt;Recognizing and quantifyingthis role, however, demands computationalstrategies that match the complexity of the systems involved: large,flexible supramolecular assemblies in which competing enantiomericpathways are separated by fractions of a kcal·mol&lt;sup&gt;–1&lt;/sup&gt;. This Account shows how such strategies enable quantitative predictionof enantioselectivity and reveal London dispersion as an often overlookedyet engineerable interaction in confined asymmetric catalysis.&lt;/p&gt;&lt;p&gt;Using imidodiphosphorimidate (IDPi) catalysts as the central casestudies, we demonstrate that an accurate description of their systemsrequires treating key intermediates and transition states as conformationalensembles rather than single structures, where the role of the solventadds a further layer of supramolecular complexity. With ensemblesranked to identify the arrangements that are thermally accessibleunder reaction conditions, electronic structure analysis enables thedisentangling of the noncovalent interactions that discriminate betweencompeting pathways.&lt;/p&gt;&lt;p&gt;Building on the combination of quantitativeaccuracy and interaction-levelinsight, we examine recent representative case studies that illustratehow London dispersion plays a crucial role in shaping function inchir","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2388–2398"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522229","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":"Repurposing Thiamine-Dependent Benzaldehyde Lyases as Visible-Light-Driven Radical Acyltransferases","authors":"Yuanyuan Xu,&nbsp;Xichao Peng,&nbsp;Xiaoqiang Huang","doi":"10.1021/acs.accounts.6c00370","DOIUrl":"10.1021/acs.accounts.6c00370","url":null,"abstract":"&lt;p&gt;Thiaminediphosphate (ThDP)-dependent enzymes are among nature’smost elegant biocatalysts for C–C bond formation and cleavage,typically operating through a two-electron umpolung mechanism. Althougha small subset of ThDP enzymes, such as pyruvate: ferredoxin oxidoreductase(PFOR), has been shown to proceed via single-electron radical pathways,this knowledge had not yet been harnessed for asymmetric radical reactions.Inspired by thiamine biocatalysis, chemists have developed biomimetic &lt;em&gt;N&lt;/em&gt;-heterocyclic carbene (NHC) complexes since the 1950s,and more recently, established radical NHC catalysis as a powerfulplatform for radical transformations. In this approach, an NHC-stabilizedketyl radical undergoes cross-coupling with a free C-centered radical.However, achieving enantioselective cross-coupling involving prochiralC-center radicals had remained an unsolved challenge with chiral chemo-NHCcatalysts. This difficulty stems from both the highly reactive natureof these open-shell intermediates and the inherent limitation of smallorgano-NHC complexes in creating a suitable and tunable chiral environment.&lt;/p&gt;&lt;p&gt;To address the above challenges, we drew inspiration from nature’sThDP-dependent biocatalysis and biomimetic chemo-NHC-based radicalpathways, developing a synergistic photoredox-/thiamine radical biocatalysisfor asymmetric radical acylations. In this system, the thiamine-dependentbenzaldehyde lyase from &lt;em&gt;Pseudomonas fluorescens Pf&lt;/em&gt;BAL activates aldehyde substrates to form catalytically active enzymaticBreslow intermediates. Visible-light-driven photoredox catalysis enablesthe concurrent formation of prochiral C-centered radicals and enzyme-boundthiamine-derived ketyl radicals. Through protein engineering, theevolved active site of &lt;em&gt;Pf&lt;/em&gt;BAL variant precisely orchestratesthe enantioselective cross-coupling of the two radical intermediates.Overall, this combination of chemomimetic and biomimetic strategiesrepurposes ThDP-dependent &lt;em&gt;Pf&lt;/em&gt;BAL into a radical acyltransferase(RAT), expanding the reactivity repertoire of enzymes and overcomingthe challenges in stereochemical control of free prochiral C-centeredradicals.&lt;/p&gt;&lt;p&gt;We first established this synergistic photoredox/thiamineradicalcatalysis through a decarboxylative radical acylation, in which prochiralC-centered radicals generated from &lt;em&gt;N&lt;/em&gt;-(acyloxy)phthalimidesunder Eosin Y-mediated photoredox conditions were selectively acylatedby &lt;em&gt;Pf&lt;/em&gt;BAL variants with benzyaldehyde as the acyldonor. Mechanistic studies confirmed the involvement of both ketyland prochiral radical intermediates. Building on this discovery, wesubsequently demonstrated the robustness of thiamine-dependent radicalbiocatalysis in diverse challenging transformations, including benzylicC(&lt;em&gt;sp&lt;/em&gt;&lt;sup&gt;3&lt;/sup&gt;)–H bonds acylation, C–Cbonds acylation via nitrogen-centered radicals, three-component radicalcross-coupling, and the construction of all-carbon quaternary stereocenterbearing minimally diff","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2487–2502"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428969","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":"Design Strategies for Developing Chiral Macrocyclic Chelators as a Diagnostic Tool","authors":"Yifan Zhu,&nbsp;Ga-Lai Law","doi":"10.1021/acs.accounts.6c00081","DOIUrl":"10.1021/acs.accounts.6c00081","url":null,"abstract":"&lt;p&gt;Macrocyclic chelators have becomean indispensable part of thefield of molecular imaging due to their ability to form highly stablecomplexes with various metal ions for diverse diagnostic and therapeuticapplications. Among them, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid), which serves as a gold standard in both stability and versatility,is extensively utilized in clinical contexts as contrast agents fora series of imaging modalities, including MRI (magnetic resonanceimaging), PET (positron emission tomography), SPECT (single-photonemission computed tomography), and optical imaging. Despite its advantageousproperties, in certain cases, DOTA still has limitations to be solved,such as slow radiolabeling kinetics and possible &lt;em&gt;in vivo&lt;/em&gt; decomplexation, which have led to increased research interest instructural modifications of the DOTA ligand.&lt;/p&gt;&lt;p&gt;To date, the mostpopular design strategy for DOTA analogues focuseson the modification of pendant arms, which can be simply achievedthrough the N-derivatization of the tetraaza macrocycle. Another strategyis to modify the macrocyclic ring structure, with the most successfulexample being the macrocycle pyclen, which contains a pyridine moiety.In 2022, pyclen-based Gd&lt;sup&gt;3+&lt;/sup&gt; complex gadopiclenol was approvedby the U.S. FDA (United States Food and Drug Administration) as anext-generation MRI contrast agent for clinical use. However, reportedstudies on similar structural modifications of macrocyclic rings arerelatively rare, as this requires the redesign of synthetic proceduresthat can be highly complicated.&lt;/p&gt;&lt;p&gt;In this Account, we discussour design strategies of various macrocyclicchelators with chiral substituents on the macrocyclic ring for differentbiomedical imaging applications. We start with structural modificationsto the frequently used DOTA chelator through the introduction of foursymmetrical chiral substituents on its macrocyclic backbone. Resultsof NMR studies confirmed that the incorporated chiral substituentscan prevent the interconversion between two TSAP/SAP regioisomersformed in the complexation process of DOTA with lanthanides. The chiralsubstituents also provide increased ligand rigidity and can enhancethe coordination geometry for better encapsulation of the metal, preventingpossible dechelation and transmetalation, thereby achieving highercoordination stability. A series of DOTA analogues with differentchiral substituents were studied, and we have revealed that the TSAP/SAPisomeric ratios and pharmacokinetics of chiral DOTA varied with thesteric hindrance and polarity of attached chiral groups. In particular,the Gd&lt;sup&gt;3+&lt;/sup&gt; complexes of chiral DOTAs with symmetric aliphaticgroups exhibit enhanced relaxivity over that of achiral DOTA, makingthem ideal contrast agents for MR imaging. Through the subsequentoptimization of introduced chiral groups, various improved chelatorswere then developed for photoluminescence or for MRI.&lt;/p&gt;&lt;p&gt;Next,we focused on fu","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2321–2335"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451466","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":"Molecular Engineering of Stimuli-Activatable Protein Degraders for Precise Cancer Therapy","authors":"Jing Gao,&nbsp;Yi Lai,&nbsp;Bo Hou,&nbsp;Yijing Dang,&nbsp;Huiling Zhou,&nbsp;Zhiai Xu,&nbsp;Haijun Yu","doi":"10.1021/acs.accounts.6c00270","DOIUrl":"10.1021/acs.accounts.6c00270","url":null,"abstract":"<p>The emerging advance of targeted protein degradation(TPD) technologyoffers a novel option for protein modulation, ensuring a more durableand precise therapeutic impact for cancer management. While promising,complete degradation of the proteins of interest (POIs) in both pathologicaland normal tissues may cause severe side effects. Furthermore, insufficientaccumulation of the protein degraders at the target tissues also limitsthe clinical translation of TPD. It remains an unmet need to achievespatiotemporally tunable degradation of the POI at the tumor lesion.In recent years, our group has extensively exploited the potentialof the stimuli-activatable TPD technology for precise cancer therapy.The stimuli-activatable protein degraders were rationally designedfor achieving tumor-specific enrichment in vivo to maximize theirtherapeutic effects while minimizing the side effects. Several kindsof stimuli-labile prodrugs of the proteolysis targeting chimeras (PROTACs)were rationally designed for restoring their protein degradation functionswith the endogenous or exogenous stimulus of tumor while remaining“silent” elsewhere, resulting in precise therapies andreduced side effects. Leveraging the advantages of nanomedicine deliverysystems, several kinds of tumor acidity and enzymatic-activatablenanodegraders were developed to achieve tumor-targeted protein degraderdistribution and POI degradation. In particular, photothermally activatableprotein degraders were developed to perform spatiotemporally controllabledegradation of various POIs.</p><p>In this Account, we systematicallysummarize recent advances fromour group regarding the rational design of stimuli-activatable proteindegraders, and strategically outline the “when and how”of integrating these degraders with nanomedicine platforms to tailorprecise cancer therapy. We discuss the crucial role of the tumor microenvironment-responsivemoieties for stimuli-triggered degradation of both intracellular andmembrane POIs, highlighting the distinct design rationale for theirrespective prodrugs. Furthermore, we summarize our advances of strategicintegration of the TPD technology with nanomedicine to augment thetherapeutic outcomes of phototherapy, radiotherapy, chemotherapy,and immunotherapy of solid tumors. It is envisaged that the tumormicroenvironment-activatable protein degradation approaches will achievetumor-specific protein degradation and precision therapy, therebyfacilitating the clinical application of TPD. By outlining optimizeddesign strategies and future challenges, this Account aims to serveas a roadmap for researchers seeking to develop next-generation activatableTPD technologies that are modular, functionally versatile, and translatable.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2348–2364"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148462700","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":"Dynamic Kinetics of MgH2 in Solid-State Hydrogen Storage: From the “Dam-Break Effect” to Mechanistic Understanding, Data-Driven Design, and Application Strategies","authors":"Jianghao Cai,&nbsp;Tongao Yao,&nbsp;Piao Ma,&nbsp;Wenfeng Fu,&nbsp;Shuai Dong,&nbsp;Di Zhang,&nbsp;Linda Zhang,&nbsp;Zhengyang Gao,&nbsp;Hao Li,&nbsp;Weijie Yang","doi":"10.1021/acs.accounts.6c00383","DOIUrl":"10.1021/acs.accounts.6c00383","url":null,"abstract":"&lt;p&gt;Gas–solid reaction kineticsdescribes how gaseous speciesinteract with solid surfaces and bulk regions in energy and materialsprocesses. This behavior is often evaluated using compact descriptors,such as onset temperature, apparent activation energy, equilibriumparameters, or rate constants. These descriptors enable comparisonacross materials and conditions, but compress a multistage reactioninto single-value metrics. The central limitation is that kineticresistance is treated as an averaged parameter, rather than as a quantitythat may emerge at a specific stage, location, or interface and evolveduring conversion. This compression becomes problematic when localcoordination, bonding, defect structure, heat transfer, mass transport,and interfaces change. MgH&lt;sub&gt;2&lt;/sub&gt; dehydrogenation provides arepresentative case. Its sluggish dehydrogenation has been assessedusing onset dehydrogenation temperature and apparent activation energy.However, the weak correspondence between these parameters, the gapbetween theoretical barriers and experimentally fitted activationenergy, and the ability of surface catalysts to improve macroscopickinetics point to a missing kinetic coordinate. This coordinate isreaction progress, which reveals how much reaction has occurred, wheredominant resistance is located, and how it is redistributed.&lt;/p&gt;&lt;p&gt;In this Account, we discuss the “dam-break effect” (originally proposed as the “burst effect”) as a reactionprogress dependent kinetic framework for MgH&lt;sub&gt;2&lt;/sub&gt; dehydrogenation.Unlike conventional single-parameter descriptions, the dam-break effectemphasizes stage-resolved evolution of kinetic resistance from aninitially high-resistance surface state to a lower-resistance regime.Microscopic calculations show that hydrogen removal from the firstsurface layer has the highest barrier, whereas subsequent hydrogendesorption and migration become easier after this layer is breached.Reconstruction of isothermal kinetic curves reveals a rapid decreasein activation energy in the early region, followed by a stable plateau.These observations suggest that the first surface layer behaves asa kinetic dam, and its removal triggers a transition from an initiallyresistant state to an accelerated regime. We then examine how thedam-break effect connects local environment evolution, surface-controlleddehydrogenation, and inconsistencies among onset temperature, apparentactivation energy, and theoretical barriers. This dynamic viewpointis extended to data-driven design, where databases, machine learning,AI agents, and machine learning potentials transform kinetic observationsinto computable descriptors. Finally, we discuss application strategiesin which materials design targets the surface and near-surface bottleneck,while system operation matches energy input to stage-dependent resistance.Using MgH&lt;sub&gt;2&lt;/sub&gt; as a model system, this Account aims to promotea broader shift in gas–solid reaction kinetics from staticparameter description toward r","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2561–2574"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432790","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":"Photoredox-Mediated Radical Smiles–Truce Rearrangement: From Aryl Migration to Molecular Complexity Generation","authors":"Sergio González-Granda,&nbsp;Mark D. Glossbrenner,&nbsp;Izabella O. Krug,&nbsp;Luke A. Farmer,&nbsp;Corey R. J. Stephenson","doi":"10.1021/acs.accounts.6c00229","DOIUrl":"10.1021/acs.accounts.6c00229","url":null,"abstract":"&lt;p&gt;The Smiles–Truce rearrangementrepresents a uniquely powerfulbut historically underutilized strategy for arene functionalization,enabling intramolecular C–C bond formation through controlledmolecular reorganization. Despite its conceptual appeal as a strategicdisconnection, its traditional implementation as a two-electron S&lt;sub&gt;N&lt;/sub&gt;Ar process has relied on strong bases and polarized reactionmanifolds, which restrict functional group tolerance, limit substratescope, and thus confine its use to relatively simple molecular settings.&lt;/p&gt;&lt;p&gt;The emergence of radical Smiles–Truce rearrangements, particularlythose enabled by visible-light photoredox catalysis, has fundamentallyaltered how this transformation can be deployed in synthesis. Ratherthan functioning only as a specialized S&lt;sub&gt;N&lt;/sub&gt;Ar variant, theSmiles–Truce rearrangement can be redeployed as a general radicalrelay for &lt;em&gt;ipso&lt;/em&gt;-selective arene functionalizationand framework reorganization. Photoredox catalysis enables mild, catalyticaccess to tethered radical intermediates that engage arenes intramolecularly,bypassing the constraints of polar reactivity and allowing the rearrangementto be applied in complex, functionalized environments. Photoredox-mediatedSmiles–Truce rearrangements proceed through the generationof carbon-centered radicals that add intramolecularly to (hetero)arenes,forming transient spirocyclic radical Meisenheimer intermediates.Fragmentation of sulfur-based leaving groups then forges new C–Cbonds in a single, efficient sequence. This radical framework enablesthe direct conversion of simple, abundant building blocks, includingsulfonyl chlorides, alcohols, amines, and olefins, into architecturallycomplex products. Importantly, multiple photoredox activation modes,such as single-electron transfer, proton-coupled electron transfer,and deprotonation–oxidation pathways, expand the strategicreach of this rearrangement and highlight its modularity.&lt;/p&gt;&lt;p&gt;Inthis Account, we illustrate how photoredox-enabled Smiles–Trucerearrangements can be strategically leveraged to achieve diverse syntheticobjectives, including arene dearomatization, alcohol-derived frameworkreorganization, and olefin aminoarylation with high diastereocontrol.We further highlight the robustness and scalability of these reactions,as well as their application to the concise synthesis of bioactivetargets. Finally, we demonstrate how transitioning from S(VI) to S(IV)intermediates enables enantiospecific variants of the Smiles–Trucerearrangement, introducing stereochemical control into a transformationlong considered stereochemically agnostic.&lt;/p&gt;&lt;p&gt;Together, these studiesshow how photoredox catalysis transformedthe Smiles–Truce rearrangement from a specialized aryl-migrationreaction into a programmable platform for molecular reorganizationand C–C bond construction. By coupling radical logic with photoredoxcatalysis, this transformation enables direct reorganization of molecularframeworks from simple precur","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2399–2411"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440980","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":"Deep Learning for Localization Microscopy in 2D and 3D","authors":"Ofri Goldenberg,&nbsp;Dafei Xiao,&nbsp;Yoav Shechtman","doi":"10.1021/acs.accounts.6c00345","DOIUrl":"10.1021/acs.accounts.6c00345","url":null,"abstract":"<p>Super-resolution microscopy has fundamentally transformed our abilityto observe biological structures, allowing nanoscale observation intobiological samples such as fixed and live cells and tissues, and hasbeen notably recognized by the 2014 Nobel Prize in Chemistry. Single-moleculelocalization microscopy (SMLM) stands out as a highly successful andwidely accessible method for super-resolution microscopy. However,because SMLM relies on computationally reconstructing a single imagefrom thousands of sparse frames, it suffers from significant algorithmicbottlenecks, particularly when dealing with high emitter densitiesor three-dimensional data. Deep learning has emerged as an exceptionallyeffective solution to bypass these computational challenges, enablingfast, parameter-free reconstruction. The application of neural networksfor SMLM analysis is uniquely powerful because such networks can betrained entirely on simulated data; since the optical point spreadfunction is well-understood, and SMLM images are fundamentally simple,consisting of a collection of point-spread functions, it is relativelyeasy to numerically simulate the vast quantities of highly accuratetraining images required to train reconstruction nets.</p><p>In thisAccount, we summarize our contributions to localizationmicroscopy by applying neural nets to address its limitations andbottlenecks. Specific challenges and applications include dense moleculefitting in 2D and in 3D, single-channel multicolor imaging, superspatiotemporal resolution microscopy, optical genome mapping, largefield-of-view (FOV) imaging, and accurate background simulation. Thefact that the training of the neural net is based on simulated imagesenables powerful and interesting capabilities. For example, the opticalsetup itself can be algorithmically designed together with the decodingneural net; we have used this concept for tasks such as designingoptimal phase masks for depth encoding, for spectral encoding, andeven for both simultaneously.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2450–2461"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589220","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}