Accounts of Chemical Research最新文献

{"title":"Beyond Partial Readouts: Toward Integrative Mechanism Inference in Catalytic Oxidation","authors":"Jing-Hang Wu,Han-Qing Yu","doi":"10.1021/acs.accounts.6c00527","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00527","url":null,"abstract":"Oxidative reactive species (ORSs) provide a shared mechanism language for catalytic oxidation in both natural systems and industrial applications. Mechanism investigation seeks to explain how these processes proceed and how they can be regulated, conventionally focusing on identifying the dominant ORS and quantifying its contribution to substrate transformation. Yet ORSs are short-lived, present at low concentrations, and are rapidly interconverting, making their mechanism roles inseparable from the complex environment in which they form, transform, and decay. Disagreements among established identification methods have consequently become a recurring source of controversy across well-studied oxidation systems.\u0000Typically, ORS participations are examined through chemical probing, quenching, or direct spectroscopic detection. The widely used chemical approaches assume that each reagent reacts selectively with a single target species, allowing an experimental response to be read as a mechanism assignment. Such selectivity is scarcely attainable where multiple reactive species coexist and interconvert, so refining reagents or instruments alone cannot reconstruct the underlying chemistry once each response is assigned to one species. Our previous work on spin-trapping electron paramagnetic resonance (EPR) exposed this vulnerability, revealing that even this widely trusted probe can enter the reaction chemistry. Reconstructing these signals into kinetic profiles successfully resolved when each reporting product forms, evolves, and decays, although temporal resolution alone cannot trace the reactions linking these stages.\u0000To organize this chemistry, we cast catalytic oxidation as a directed reactive species network, mapping each reactive species onto a node and every route of generation, interconversion, transformation, and dissipation onto an edge. External substrates or reporters couple to these nodes through distinct reactions weighted by their rate constants. Therefore, ORS dominance is not an intrinsic property of any node but a condition-dependent property of the network, set by how reaction conditions distribute reactive flux and by the substrate or reporter through which the network is read. Whether through probing, quenching, or direct detection, each measurement returns a low-dimensional projection of this high-dimensional network, so conflicting assignments may reflect one dynamic mechanism rather than incompatible chemistries. Recovering the hidden organization behind these partial projections thus becomes an inverse problem.\u0000In this Account, we revisit current ORS identification strategies, examine how chemical, kinetic, and spectroscopic evidence constrains mechanism interpretation, and present a network basis for reconstructing the hidden chemistry behind the resulting observations. Realizing this route appeals to AI-assisted inference under chemist-centered judgment and to structured databases built under this network view through automat","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"2 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149250823","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":"Selenium-Containing Polymers: In Vivo Modulation and Radioprotection","authors":"Wei Chen,Ruotong Deng,Yang Cheng,Wei Cao,Huaping Xu","doi":"10.1021/acs.accounts.6c00478","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00478","url":null,"abstract":"Selenium is an essential element widely utilized across biological systems, where it imparts unique chemical functionality to biomacromolecules. While selenoproteins are well appreciated in humans, other selenium-containing biomacromolecules remain largely absent, and the development of selenium-based therapeutics has lagged. Here, from the perspective of molecular design, we introduce a series of selenium-containing polymers with diverse molecular structures and elucidate their in vivo effect, aiming to advance selenium chemistry toward defined biological functions. In this account, we establish a unified framework linking molecular structure, chemical reactivity, and in vivo functionality of selenium-containing polymers, thereby redefining their role beyond conventional drug carriers. We first delineate the distinct redox-responsive behaviors of monoselenide and diselenide motifs and their divergent biological consequences in vivo. We then introduce selenium-doped carbonized polymer dots for the treatment of liver and kidney diseases. Finally, we discuss selenium-containing melanins as a previously unrecognized class of selenium-enriched biomacromolecules with exceptional radioprotective capability, arising from their conjugated structures and selenium-specific electronic properties. By integrating these structurally related yet functionally diverse systems, this account highlights general design principles for in vivo modulation using selenium polymer chemistry. Bridging the gap between biological selenium utilization and synthetic molecular design unlocks new opportunities for selenium-based therapeutics and establishes selenium-containing polymers as a distinctive platform in biomedical science.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"10 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149250819","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":"Programming Photodynamic Therapy with Glycopolymeric Photosensitizers: From Carbohydrate Recognition to Light-Activated Nanomedicine","authors":"Jiahui Lin,Weiwei Zuo,Zhiyuan Ma,Martina H. Stenzel","doi":"10.1021/acs.accounts.6c00627","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00627","url":null,"abstract":"Glycopolymers are synthetic macromolecules that display multiple carbohydrate motifs and mimic the multivalent presentation of glycans in biological systems. Advances in controlled polymerization now allow chain length, sugar density, sequence, composition, and topology to be tuned with increasing precision. As a result, glycopolymers have progressed from models of carbohydrate-lectin recognition to materials for receptor- and transporter-mediated targeting, drug delivery, and precision therapy. Studies of fructose-containing micelles showed that cellular interactions depend not only on sugar identity or total sugar content but also on chain length, local density, spatial arrangement, and carbohydrate accessibility. These principles were then applied to drug delivery, where polymer composition and self-assembly improved the aqueous encapsulation of poorly soluble drugs, regulated nanoparticle size, and promoted intracellular distribution. Glycopolymers therefore became functional materials that control both biological recognition and the organization of therapeutic molecules.\u0000Glycopolymeric photosensitizers extend this concept to photodynamic therapy (PDT), in which photosensitizers convert light into localized photochemical effects. Porphyrins are attractive because of their optical properties and ability to generate reactive oxygen species (ROS), but their use is limited by poor aqueous dispersibility, aggregation, nonspecific uptake, altered photochemical activity, and inadequate intracellular localization. Photosensitizer delivery is therefore not simply a solubilization problem; it requires coordinated control over molecular organization, biological targeting, and intracellular transport. Glycopolymers can address these challenges through physical loading or covalent incorporation. Physical loading is simple and adaptable but may provide limited control over loading and retention, whereas covalent attachment allows more precise regulation of photosensitizer content and placement. To combine photosensitizer organization with carbohydrate-mediated targeting, we developed several covalent glycopolymeric photosensitizers. Porphyrin-containing random and block glycopolymers revealed how polymer sequence influences aggregation, intracellular ROS generation, and photocytotoxicity. Porphyrin-core star glycopolymers further showed that arm length, carbohydrate identity, and corona composition affect recognition, uptake, and PDT response, while related systems enabled combined therapeutic functions. Their synthesis also evolved from conventional ATRP, which requires added catalytic systems and does not directly link photosensitizer function with polymer formation, toward light-mediated polymerization. In photoATRP, we developed a triple-function zinc porphyrin that serves as initiator, photocatalytic component, and photosensitizer. A complementary self-photocatalyzed PET-RAFT strategy used a polymerizable porphyrin that participates in polymerization ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"5 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149248656","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":"Evolution of Aggregation-Induced Emission Materials in Cancer Diagnosis and Therapy: Toward Clinical Translation","authors":"Qi Li,Guo Zhao,Hanchen Shen,Zhenfeng Huang,Tingyi Chen,Mengyue Shi,Tianfu Zhang,Ben Zhong Tang,Shipeng Ning","doi":"10.1021/acs.accounts.6c00511","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00511","url":null,"abstract":"As one of the most formidable threats to human health, cancer demands technologies that can sensitively detect malignancies, precisely guide intervention, adapt to dynamic disease states, and support clinical decision-making. Phototheranostics based on organic fluorophores have shown great promise in cancer management owing to their tunable structural design, tumor-targeting capability, real-time imaging output, and biocompatibility with diverse therapeutic modalities. However, conventional fluorophores often suffer from aggregation-caused quenching in concentrated or biological aggregate states, leading to weakened signals, insufficient sensitivity, and limited therapeutic efficacy. The discovery of aggregation-induced emission (AIE) provides a conceptually distinct solution to this problem. AIE materials are weakly emissive in the molecularly dispersed state but become highly luminescent upon aggregation, thereby turning aggregation from a detrimental process into a useful photophysical mechanism. By precisely controlling molecular motion, AIE materials can exhibit advantages including high signal-to-noise ratio, large Stokes shifts, and excellent photostability, making them a versatile molecular toolbox for tumor-oriented phototheranostic systems. Over the past two decades, they have evolved beyond simple fluorescent probes into integrated platforms for cancer theranostics.\u0000In this Account, we propose a concept-driven framework, termed AIMS (Analyze-Intervene-Modulate-Select), to organize the evolution of AIE materials in cancer diagnosis and therapy according to their distinctive roles within cancer management. The first generation, “Analyze”, refers to AIE materials used mainly as diagnostic tools. These systems enable sensitive detection of tumor-associated biomarkers, in vivo lesion visualization, and multimodal intraoperative identification. The second generation, “Intervene”, generates all-in-one theranostic platforms that couple imaging with phototherapy, facilitating radiotherapy sensitization, immune activation, or postoperative control. The third generation, “Modulate”, describes intelligent and adaptive AIE platforms that respond to therapy-induced stress, microenvironmental shifts, or dynamic biological feedback during treatment, transforming static theranostics into systems capable of modulating therapeutic trajectories. The emerging fourth generation, “Select”, represents a data-driven paradigm linking the design of AIE materials with artificial intelligence, multiomics, patient stratification, model selection, and indication prioritization. Through AIMS, we organize the accumulated capabilities of AIE materials around four functional roles. By clarifying which role is most relevant to a given application, AIMS guides future research in prioritizing design objectives, integrating the functions needed for the intended task, and matching material innovation to specific needs in cancer management.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"79 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241413","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-Efficiency Excimer Luminescence from Discrete π–π Stacked Dimers","authors":"Haichao Liu,Bing Yang","doi":"10.1021/acs.accounts.6c00460","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00460","url":null,"abstract":"Molecular aggregates serve as an important platform for the practical applications of organic luminescent materials. Within these aggregates, both molecular arrangements and intermolecular interactions provide crucial avenues for modulating the luminescence properties. Given that organic chromophores are typically characterized by planar and rigid π-conjugated units, π–π stacking and π–π interactions are determinative for the formation of aggregates and the regulation of photophysical properties. However, strong π–π stacking usually leads to luminescence quenching in organic aggregates, due to the forbidden radiative transition and the activated nonradiative transition. Specifically, the strong π–π stacking facilitates the formation of excited dimers, i.e., excimers, and these excimers have long been regarded as “dark” states that are detrimental to luminescence. This inherent quenching effect is in conflict with the requirement for high luminescence efficiency of organic materials in optoelectronic applications.\u0000In this Account, we highlight our recent findings: strong π–π stacked dimers can achieve high-efficiency excimer luminescence when they are spatially discrete in aggregates. The findings stem from the crystal packing structure observation of a thianthrene-modified anthracene compound, which exhibits a unique discrete π–π dimer stacking of anthracene with an unexpectedly high photoluminescence quantum yield (Φ) of 80%. Theoretical and experimental investigations reveal that this discrete π–π dimer stacking promotes the formation of a pure and single excimer state. Building on this, high-efficiency excimer luminescence can be ascribed to the special nature of this excimer state: a hybridized local and charge-transfer state, which consists of two locally excited components of the monomers and two charge-transfer components between the two monomers. Compared to the monomer, although the radiative transition rate of the excimer is reduced by 2 orders of magnitude, the suppression of nonradiative transition rate is even more significant. The combined effect of these factors enables high-efficiency excimer luminescence to be achieved in discrete π–π stacked dimers.\u0000Based on these findings, a molecular design principle was proposed to construct the discrete π–π stacked dimers. The molecular structure consists of two moieties: a planar aromatic core (π moiety) and a unilateral substituent (side moiety). On the one hand, the unilateral substituent is attached to the π moiety to guarantee the dimer formation in antiparallel π–π stacking with the aid of steric hindrance. On the other hand, two substituents can act as the spacers to isolate the formed π–π dimers from each other by means of their appropriate size and orientation. To verify the universality of this design strategy, various π and side moieties were combined together to prepare a series of crystalline materials with discrete π–π stacked dimers and tunable emission colors. Furthermore, th","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"21 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241460","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":"Precision Protein Modification via Ligation and Bioconjugation at Selenocysteine","authors":"Max J. Bedding,&nbsp;Sameer S. Kulkarni,&nbsp;Richard J. Payne","doi":"10.1021/acs.accounts.6c00543","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00543","url":null,"abstract":"<p>Selenocysteine (Sec), oftenreferred to as the21st amino acid,is a rare yet essential amino acid found in a small number of naturallyoccurring selenoproteins that play critical roles in redox regulation,antioxidant defence, and hormone metabolism. Owing to its distinctchemical properties, namely enhanced nucleophilicity, lower reductionpotential, and versatile redox behaviour of the side chain selenol/diselenidemoiety relative to the thiol/disulfide of Cys, Sec has recently beenleveraged for a range of applications in protein science.</p><p>Inthis account, we summarize our endeavors towards the developmentof selenium-mediated ligation methodologies for the rapid and highlyefficient assembly of proteins, including those bearing native post-translationalmodifications (PTMs) or “designer” modifications. Keyinnovations include the diselenide–selenoester ligation (DSL)and expressed protein selenoester ligation (EPSL). DSL enables therapid fusion of unprotected peptides through a chemoselective reactionbetween peptide selenoesters and selenopeptides. Notably, in the presenceof suitable additives, DSL can be performed at nanomolar concentrations,providing access to challenging classes of modified proteins, suchas lipoproteins, that are difficult to access via other techniques.We also discuss the extension of DSL chemistry to larger proteinsthrough the generation of protein selenoesters from recombinantlyexpressed intein fusion proteins. By combining the advantages of recombinantbacterial expression and the rapid kinetics of DSL at Sec, we highlightthe use of the EPSL technology for the generation of large, aggregation-proneproteins, including the lipidated GTPase YPT6 and mycobacterial lipoproteinsas novel vaccine antigens. Beyond protein synthesis and semi-synthesis,we have also demonstrated the utility of selenocysteine (Sec) as apowerful bioconjugation handle. Specifically, we highlight two novelSec-selective bioconjugation reaction manifolds in this account; thephotocatalytic diselenide contraction (PDC) and electrochemical selenoetherification(e-SE). These transformations enable dimerization and site-specificfunctionalization of peptide and protein diselenides with exceptionalregio- and chemoselectivity, offering significant advantages overother bioconjugation methods.</p><p>Overall, we believe that thesetechnologies represent a major advancein the generation of site-selectively modified peptides and proteins,unlocking new possibilities for applications in fundamental biologybut also the generation of next-generation diagnostics and therapeuticsbearing precise modifications at defined sites on proteins.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 20","pages":"3450–3462"},"PeriodicalIF":18.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218980","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":"Cross-Scale Supply–Demand Matching of Reactive Species in Electrocatalytic Reduction Reactions","authors":"Huai Qin Fu,&nbsp;Peng Fei Liu,&nbsp;Porun Liu,&nbsp;Hua Gui Yang,&nbsp;Huijun Zhao","doi":"10.1021/acs.accounts.6c00559","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00559","url":null,"abstract":"&lt;p&gt;Electrocatalytic reduction reactions,such as the hydrogen evolutionreaction (HER) and the carbon dioxide, carbon monoxide, and nitrogenelectroreduction reactions (CO&lt;sub&gt;2&lt;/sub&gt;RR, CORR, NRR), providepromising and sustainable routes for energy conversion, carbon utilization,and low-emission chemical manufacturing. Despite significant advancesin catalyst development, the practical implementation of these reactions,particularly under high-current-density conditions, remains severelyconstrained by inefficiencies in activity, selectivity, and stability.The electrocatalyst performance has traditionally been interpretedand optimized largely in terms of intrinsic activity descriptors,such as adsorption free energies of reaction intermediates, electronic-statecharacteristics of active sites, and related electronic-structureparameters, including the d-band center and density of states. Thesedescriptors are typically evaluated in modeling under the implicitassumption that reactive species are continuously and sufficientlysupplied to catalytic active sites. Under practical operating conditions,especially at high reaction fluxes, however, this assumption is oftenno longer valid. A critical limitation arises from the mismatch betweenthe supply capacity of reactive species (e.g., *H, lattice O, andCO&lt;sub&gt;2&lt;/sub&gt;) and the demand strength imposed by active sites. Athigh current densities, electrochemical interfaces operate far fromequilibrium, such that reaction performance is no longer governedsolely by the intrinsic catalytic activity of a single active sitebut also by the rates of generation, replenishment, transfer, andutilization of elementary reaction species. Such supply–demandimbalances can reduce overall reaction rates and alter reaction pathways.However, the role of species supply–demand matching acrossdifferent scales has rarely been systematically incorporated intoreaction mechanisms or catalyst design strategies.&lt;/p&gt;&lt;p&gt;In this Account,we propose a reactive species cross-scale supply–demandmatching framework in electroreduction reactions across atomic, nanoscale,and macroscale regimes. We demonstrate that catalytic performanceis governed not only by intrinsic activity but also by whether theavailability of reactive species becomes insufficient, excessive,or appropriately matched to the demand of active sites. At the nanoscale,we uncover hydrogen spillover as an interfacial mechanism that couples*H generation and consumption sites, enabling *H supply–demandbalance in alkaline HER. At the atomic scale, extending this conceptto proton-coupled electron transfer reactions reveals that efficienthydrogen transfer is governed by spatial proximity, requiring angstrom-scalesite separation. Furthermore, we identify lattice oxygen as an alternativeatomic-scale supply pathway in CO&lt;sub&gt;2&lt;/sub&gt;RR and provide directexperimental evidence for lattice oxygen participation. At the macroscale,we develop quantitative CO&lt;sub&gt;2&lt;/sub&gt; supply–demand matchingmodels that co","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 20","pages":"3437–3449"},"PeriodicalIF":18.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218984","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":"Chemically Induced Proximity for Targeted Protein O-GlcNAcylation","authors":"Bowen Ma,&nbsp;Tongyang Xu,&nbsp;Zhihao Guo,&nbsp;Billy Wai-Lung Ng","doi":"10.1021/acs.accounts.6c00453","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00453","url":null,"abstract":"<p><em>O-</em>GlcNAcylationis a ubiquitous post-translationalmodification across the mammalian proteome, yet determining how individual <em>O-</em>GlcNAcylation events control specific protein functionsremains a central challenge. The <em>O-</em>GlcNAc cycle isgoverned by two enzymes: <em>O-</em>GlcNAc transferase (OGT),which installs <em>O-</em>GlcNAc, and <em>O-</em>GlcNAcase(OGA), which removes it. Because these enzymes act on thousands ofproteins, conventional methods, such as pharmacological inhibitionof OGT or OGA, produce broad cellular effects that are difficult toassign to individual substrates. This gap has motivated the developmentof targeted <em>O-</em>GlcNAcylation strategies, includinggenetically encoded and chemical biology tools, which have shown that <em>O-</em>GlcNAc can be selectively installed on defined proteinsto interrogate protein-specific <em>O-</em>GlcNAc functions.</p><p>This Account describes the development of <em>O-</em>GlcNAcTArgeting Chimeras, or OGTACs, as chemical tools for targeted <em>O-</em>GlcNAc installation. OGTACs are bifunctional moleculesthat can recruit OGT to a specific protein of interest. Specifically,an OGTAC consists of an OGT-engaging element, a linker, and a target-recognitionmotif, which together bring OGT into proximity with a selected substrate.</p><p>Our studies show that chemically induced proximity can redirectOGT toward selected proteins, thereby creating targeted <em>O-</em>GlcNAc writing that can partially bypass TPR-domain-mediated substraterecognition under engineered recruitment conditions. A central lessonis that productive <em>O-</em>GlcNAc writing requires notonly recruitment, but also proper ternary-complex formation and noninhibitoryOGT engagement. Moreover, the target-recognition motif determinesthe targetable protein space and achievable selectivity of the platform.By linking local <em>O-</em>GlcNAc installation to changesin protein turnover, signaling, and transcriptional output, OGTACsprovide a conceptual framework for using induced proximity to modulateprotein functions.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 20","pages":"3336–3346"},"PeriodicalIF":18.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218991","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":"Developing Sustainable Chemistry with AI","authors":"Jiyizhe Zhang,&nbsp;Polina Yaseneva,&nbsp;Alexei Lapkin","doi":"10.1021/acs.accounts.6c00552","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00552","url":null,"abstract":"&lt;p&gt;Today we are experiencing anunprecedentedly rapid transformationof science, driven by advances in computing and artificial intelligence(AI). At the same time, there are growing cumulative pressures ofclimate change impacts that not only affect economies but are creatingsignificant societal challenges. The confluence of technology pushand environmental–socioeconomic pressures is promoting thedevelopment of sustainable chemistry. The link between the transitionto sustainability in chemistry and the digital transformation of R&amp;Dand manufacturing has been the long-standing focus in our research(Fantke, P.; et al. &lt;em&gt;Chem&lt;/em&gt; &lt;strong&gt;2021&lt;/strong&gt;, &lt;em&gt;7&lt;/em&gt;, 2866 doi: 10.1016/j.chempr.2021.09.012). Sustainabilityis not a feature of a single chemical product or a process. It isincorrect to talk about “sustainable polyethylene”,as such narrow framing will miss many issues in the more holisticsystem that not only includes the cradle-to-grave life cycle emissionimpacts of polyethylene but also considers all aspects of equity,impact on biodiversity, resilience of supply chains, etc. Sustainablechemistry makes sense only as a complex system. An analysis of complexsystems requires large amounts of data and the use of appropriateanalytical tools, such as advanced machine learning techniques.&lt;/p&gt;&lt;p&gt;The chemical industry has been an early adopter of digital technologies,motivated by the inherent complexity of chemical systems and the needfor efficiency to stay economically competitive. As early as the 1970s,cheminformatics tools were introduced to support structure–propertyanalysis. In the 1980s, we saw the broad adoption of process modelingand simulation tools for design, scale-up, and optimization of chemicalprocesses, paralleled with developments in the field of process systemengineering and control. Today’s digital transition is muchdeeper; everything from scientific discovery (molecules, materials,and phenomena) to chemical process development, analytical methodsand process analytical technologies, and plant operation is beingreshaped. This deep transformation includes the development of a radicallydifferent approach to data in chemistry. Advances in self-drivinglaboratories, agentic AI workflows, and digital factories requireaccess to structured, semantically rich data.&lt;/p&gt;&lt;p&gt;In this Account,we focus on three key areas of digitalizationand AI technologies advancing chemistry and chemical process developmenttoward net-zero targets. First, we discuss how data mining tools areused to analyze the existing value chains and identify opportunitiesto integrate net-zero feedstocks. When new molecules are introduced,data-driven route planning can be employed to design alternative syntheticpathways, which then need to be rigorously evaluated. Second, we focuson how to use AI to accelerate discoveries in chemistry, includingthe innovative design of catalysts, rational selection of solvents,and identification of optimal reaction conditions. By leveraging st","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 20","pages":"3426–3436"},"PeriodicalIF":18.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219022","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":"From Direct to Alternating Current Electrosynthesis: Transition-Metal-Catalyzed Oxidative Cross-Coupling with Hydrogen Evolution","authors":"Qinghong Yang,&nbsp;Zhengze Wu,&nbsp;Yi Zhao,&nbsp;Bufan Dang,&nbsp;Li Zeng,&nbsp;Aiwen Lei","doi":"10.1021/acs.accounts.6c00562","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00562","url":null,"abstract":"<p>Electrochemical transition-metalcatalysis is an effective yetunderexplored platform for molecular construction. Combining the advantagesof electrochemically driven oxidation processes with the selectivitycontrol afforded by transition-metal catalysis, this field is characterizedby a rich variety of reaction types, mild conditions, and high controllability.However, it has long faced major scientific challenges: there is amismatch between electron transfer on the electrode surface and therate of catalyst-mediated reactant activation in solution, which complicatesprecise control over reaction selectivity, and metal catalysts (especiallyPd, Ag, and Cu) are prone to reductive deactivation, leading to prematuretermination of the reactions. To address these challenges, our grouphas developed three main strategies using oxidative cross-couplingreactions as a representative. First, in direct current (DC) electrosynthesis,we employed a divided cell to prevent the metal catalyst from migratingto the cathode. Second, under specific ligand and solvent combinations,we realized electro-oxidative metal-catalyzed reactions in an undividedcell by precisely controlling the redox potential. To this end, thesubstrates were equipped with directing groups (DGs) capable of chelatingwith the metal cation or an extra ligand was introduced into the reactionsystem, both of which effectively suppressed reductive deactivation.Through this approach, we successfully achieved a series of Pd-, Co-,and Mn-catalyzed oxidative C–H functionalization reactions.Third, we developed an unsymmetrical alternating current (AC)-drivenmetal catalysis strategy designed to accommodate a broader range ofreaction patterns. By precisely adjusting the duty ratio and currentof the AC waveform, we ensured smooth reactivation of the metal catalyst.This programmed waveform further enabled the maintenance of a highconcentration of the active metal species through a dynamic balance.Consequently, we successfully achieved Cu-, Ag-, and Pd-catalyzedoxidative C–H cross-coupling reactions. The synthetic utilityof AC was validated across a diverse set of mechanistic pathways,including C–H activation, radical relay, radical addition,and nucleophilic addition. We propose that AC can serve as a generaland robust platform to circumvent the persistent issue of metal catalystdeactivation in electrosynthesis. Overall, we have developed threestrategies from DC to AC electrosynthesis to address long-standingissues in electrochemical transition-metal catalysis. In contrastto the well-established DC electrosynthesis, the AC mode demonstratesa greater potential and diversity in transition-metal catalysis. Fullyexploiting the unique capabilities of AC to expand the applicationscenarios is of considerable scientific significance and practicalvalue.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 20","pages":"3463–3480"},"PeriodicalIF":18.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218987","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}