Accounts of Chemical Research最新文献

{"title":"Cobalt-Catalyzed Asymmetric Reductive Addition to Carbonyls and Related Polarized Unsaturated Bonds","authors":"Xianqing Wu,Yifeng Chen","doi":"10.1021/acs.accounts.6c00642","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00642","url":null,"abstract":"The catalytic asymmetric construction of carbon–carbon bonds through the addition of carbon-based fragments to carbonyl compounds represents a fundamental transformation in organic synthesis, providing direct access to enantioenriched alcohols and amines that are ubiquitous structural motifs in pharmaceuticals, natural products, and functional molecules. Classical approaches typically rely on stoichiometric organometallic reagents, such as Grignard and organolithium reagents, which suffer from intrinsic limitations including air and moisture sensitivity, restricted functional group compatibility, and the requirement for preformed nucleophilic reagents. These drawbacks often increase synthetic complexity and reduce overall efficiency. Therefore, the development of catalytic asymmetric addition strategies that directly utilize stable and readily available precursors, while avoiding the preparation of sensitive organometallic intermediates, represents a longstanding and highly desirable goal. In this context, reductive coupling of organic halides as latent carbon nucleophiles offers an attractive alternative strategy. The seminal Nozaki–Hiyama–Kishi (NHK) reaction established the feasibility of directly employing organic halides in carbonyl additions; however, its reliance on chromium catalysis and stoichiometric metal reductants limits its practicality and broader application. Despite substantial advances, the development of general catalytic asymmetric methods capable of controlling radical-mediated carbon–carbon bond formation, particularly for constructing sterically congested tetrasubstituted stereocenters and contiguous stereogenic centers, remains a formidable challenge.\u0000The pursuit of sustainable and efficient catalytic processes has stimulated growing interest in earth-abundant first-row transition metals, among which cobalt has emerged as a particularly promising catalyst because of its rich single-electron redox chemistry, versatile coordination behavior, and intrinsic ability to mediate radical transformations. In this Account, we summarize our recent efforts in exploiting cobalt catalysis for the asymmetric reductive addition reactions of carbonyl-derived electrophiles and related polarized unsaturated systems with organic halides. This strategy, herein termed cobalt-catalyzed asymmetric reductive addition (CARA), utilizes readily available metal reductants under mild conditions and enables stereocontrolled radical addition processes directed by chiral cobalt complexes. Through this platform, we have developed modular approaches for the synthesis of diverse enantioenriched molecules, including amino acids, alcohols, amides, and sulfinamides, directly from readily available precursors. The development of this catalytic platform is discussed from three perspectives according to the reaction partners: (1) asymmetric reductive addition of simple organohalides for the construction of sterically demanding tetrasubstituted stereocenters; (2) e","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"24 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149360426","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 Membranes to Catalyst Layers: Molecular and Interfacial Design of Anion-Exchange Polyelectrolytes","authors":"Wanjie Song,Buyuan Zhang,Xiaolin Ge,Tongwen Xu","doi":"10.1021/acs.accounts.6c00727","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00727","url":null,"abstract":"Sustainable electrochemical energy conversion relies on functional materials that enable efficient transport while withstanding demanding operating environments. Anion-exchange membrane fuel cells (AEMFCs) and anion-exchange membrane water electrolyzers (AEMWEs) are attractive platforms because their alkaline environments enable the use of nonprecious-metal catalysts and hydrocarbon-based polymer electrolytes. Anion-exchange polyelectrolytes (APEs) are central to these devices, serving as both free-standing anion-exchange membranes (AEMs) and catalyst-layer anion-exchange ionomers (AEIs). Although AEMs and AEIs share related polymer chemistries, their distinct operating environments and functional roles impose different requirements on molecular design.\u0000Our work on AEMs has focused on the coupled requirements of hydroxide transport, chemical stability, dimensional control, and mechanical durability. We first examined how polymer architecture and chain packing affect the formation of ion-conducting domains and confined transport environments. As conductivity improved, chemical degradation and mechanically induced failure became increasingly relevant, leading us to investigate cation stability, local electronic environments, dimensional constraints, and molecular-level stress dissipation. These studies showed that AEMs cannot be optimized on the basis of a single performance metric but instead require the coordinated regulation of ion transport, molecular stability, and mechanical response. We also extended this work to kilogram-scale polymer synthesis and continuous roll-to-roll membrane fabrication, where synthetic reproducibility and processing compatibility become additional constraints on molecular design.\u0000The requirements change when APEs are used as catalyst-layer ionomers. AEIs form nanometer-scale films around catalyst particles and must provide local hydroxide conduction while allowing water and gas transport, maintaining catalyst accessibility, and contributing to interfacial integrity. Our studies on AEIs have therefore examined multiphase transport, catalyst-ionomer interactions, interfacial adhesion, ionomer distribution, and catalyst-layer structure. Fluorinated and porous ionomers were used to regulate oxygen transport and gas-bubble removal, while conformational and interfacial design was used to reduce unfavorable catalyst-ionomer interactions. Further control of adhesion, ionomer-film organization, and catalyst immobilization showed that catalyst-layer performance also depends strongly on how the ionomer is distributed and organized during electrode formation.\u0000The studies discussed in this Account suggest that APE molecular design should be matched to the specific operating environment and functional role of the polymer within the membrane-electrode assembly. For AEMs, this includes balancing transport, durability, and manufacturability; for AEIs, it additionally requires control of local transport, catalyst interactions, and cat","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"498 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149360420","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":"Chemical Ordering of High-Entropy Nanomaterials for Pathway-Directed Electrocatalysis","authors":"Lele Liu,Xuan Zheng,Han Zhu","doi":"10.1021/acs.accounts.6c00550","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00550","url":null,"abstract":"High-entropy nanomaterials (HEMs) have emerged as versatile electrocatalytic platforms, because their multielement compositions provide diverse electronic configurations and coordination environments. However, high configurational complexity alone does not define the catalytic sites. Differences in elemental interactions and reduction kinetics can lead to segregation, phase separation, and structural heterogeneity, while random site occupation complicates the identification of catalytic sites and structure–activity correlations. High-entropy chemical ordering (HECO) addresses this challenge by organizing selected elements over defined spatial scales while retaining the multielement diversity. Drawing on our studies and related works, this Account describes three connected strategies. Electrospinning-enabled coordination confinement uses metal–polymer coordination and a polymer-derived carbon matrix to establish homogeneous multielement phases and regulate atomic transport. Directional atomic migration organizes selected elements at surfaces and interfaces through segregation, exsolution, and migration trapping. Diffusion-mediated bulk ordering produces preferential occupation of crystallographic sublattices and long-range ordered high-entropy intermetallics (HEIs). Local electronic polarization and intermediate adsorption help determine the elementary steps favored at different sites, while structural evolution under operating conditions can modify these relationships. Spatial organization can influence the intermediate transfer, reaction selectivity, and competing pathways. These considerations can guide the design of new surface-, interfacial-, and bulk-ordered HEMs with catalytic functions tailored to pathway-directed electrocatalysis.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"5 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149359477","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":"Watching Chemistry Across Ages via Synchrotron Radiation X-ray Microimaging Techniques","authors":"Marine Cotte,Victor Gonzalez,Clément Holé,Letizia Monico","doi":"10.1021/acs.accounts.6c00520","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00520","url":null,"abstract":"While this special issue highlights various developments and applications of ultrafast imaging techniques, our focus here is on significantly longer time scales. Instead of examining dynamic systems at submillisecond resolutions, we explore how imaging methods can be utilized to analyze materials that are static at the time scale of data collection to trace reactions that occurred years, decades, or even centuries ago. Some ongoing reactions were quenched at the time of object creation and provide insights into the manufacturing processes used by past civilizations. Others have developed beyond the initial creation of the object, either through deliberate techniques, such as prolonged drying processes in paintings, or via incidental factors that may ultimately cause degradation. It is generally assumed that a rapid chemical reaction indicates artists’ intentions, while reactions occurring over months or years are typically viewed as alterations rather than intentional processes. Therefore, the rate of chemical reactions and their chronology is a crucial factor for scholars for distinguishing between original and nonoriginal materials. When analyzing fragments from cultural heritage objects, it is essential to assess not only the chemical nature of constituents but also their spatial distribution. This information can provide valuable insights into the physical and chemical processes involved in their formation (dissolution, diffusion, precipitation, reduction/oxidation...), as well as their potential origin. Synchrotron radiation (SR)-based micro-X-ray techniques offer both the chemical sensitivity and lateral resolution necessary for these applications.\u0000Below, we present three representative examples of study of chemical processes in heritage science. The first case demonstrates how a fragment from an artwork or a craft object can offer insights into the technical and artistic practices developed centuries ago. This is illustrated through studies that elucidate the physicochemical phenomena involved in the production of ancient ceramic glazes from various archeological contexts, such as brown glazes from Song China (10−12th-century) and luster glazes from the Abbasid Caliphate (8−13th-century). The second case examines the reactions involved in degradation phenomena, highlighting that certain heritage materials can be dynamic over periods of months or years. This example also emphasizes the importance of preparing and analyzing mock-up samples to study their evolution under natural and artificial aging conditions. This case is demonstrated with several examples of pigment degradation in paintings, with a focus on the emerald green used by James Ensor (1860–1949) and Robert Delaunay (1885–1941). Finally, the last case shows that, in some cases, attributing the origin of a chemical compound to a material intentionally used by the artist or to degradation phenomena is not straightforward. This is illustrated by the analysis of the origin of differe","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"31 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149359478","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":"Planar-Chiral Cyclophanes: From Synthetic Strategies to Configurational Stability Control","authors":"Ting Yao,Changgui Zhao","doi":"10.1021/acs.accounts.6c00729","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00729","url":null,"abstract":"Planar-chiral cyclophanes, which feature rigid aromatic ring conformations locked by flexible ansa chains, are structurally distinctive scaffolds found in bioactive natural products and pharmaceutical agents. They are also widely employed as privileged frameworks in asymmetric catalysis and as functional materials. The intrinsic conformational strain of these macrocycles confers enhanced configurational stability and improved cell permeability, which are properties that are particularly appealing for drug development and chiral material design. Despite their structural significance, precise control over the rotational barrier of the aromatic ring and reliable prediction of the conformational behavior of the ansa chain remain challenging, thereby impeding both methodological advancement and practical applications of planar-chiral cyclophanes. Consequently, the development of efficient asymmetric synthetic routes and systematic investigations of their configurational stability are of paramount importance.\u0000This Account reviews the asymmetric catalytic strategies reported by our group, which have enabled the synthesis of over 500 optically active cyclophanes. Type I and Type II cyclophanes, accessed by installing bulky substituents on the aromatic ring and shortening the ansa chain, have been efficiently assembled via Pd-catalyzed C–H activation, N-heterocyclic carbene (NHC)-catalyzed oxidative esterification, and chiral phosphoric acid (CPA)-catalyzed transfer hydrogenation. These methodologies exhibit broad substrate scope and are compatible with the late-stage structural diversification of drug molecules. Importantly, these studies elucidated the intrinsic relationship between the occurrence of planar chirality and two key determinants, namely, the steric hindrance of the aromatic substituents and the length of the ansa bridge.\u0000Our previous studies have also revealed that replacing the benzene ring with an indole ring further influences macrocyclic stability. Consequently, indole-based planar-chiral cyclophanes have been constructed via a Rh-catalyzed C–H activation/intramolecular oxidative annulation with high enantioselectivities. This approach enables macrocyclization, indole ring formation, and planar chirality control in a single step and is further applicable to the synthesis of challenging derivatives bearing all-carbon ansa chains.\u0000Subsequently, this Account examines the more structurally intricate Type III cyclophanes, revealing that a cooperative NHC/CPA-catalyzed macrolactonization and a CPA-catalyzed asymmetric macrocyclization enabled the formation of Type III cyclophanes bearing either a distal quaternary carbon stereocenter or a benzylic stereocenter on the ansa chain. Relative to their unsubstituted counterparts, these Type III cyclophanes exhibit higher rotational barriers. Notably, the introduction of a naphthyl group at the benzylic position permits a two-atom extension of the ansa chain without compromising the planar chirality","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"9 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305302","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 Chlorogermanes to Carbon–Germanium Bonds: Electrochemical Strategies for Modular Germylation","authors":"Haifeng Chen, Magnus Rueping","doi":"10.1021/acs.accounts.6c00633","DOIUrl":"10.1021/acs.accounts.6c00633","url":null,"abstract":"<p>Organogermanium compounds have attracted growinginterest in materialsscience, medicinal chemistry, and catalysis because of their distinctiveelectronic properties, tunable steric environments, high chemicalstability, and emerging utility as bioisosteric motifs. Despite theseattractive features, the development of general and modular methodsfor carbon–germanium (C–Ge) bond formation has laggedthat of silicon and tin. Conventional approaches frequently rely onpreformed organometallic reagents, hydrogermanes, or stoichiometricchemical reductants, thereby limiting functional-group compatibilityand the direct use of readily available organic electrophiles.</p><p>Electrochemical synthesis offers an alternative strategy in whichelectron transfer can be regulated through electrode potential, current,catalyst identity, and cell configuration. In this context, chlorogermanesare particularly attractive germylating reagents because they arereadily accessible, bench-stable, and structurally tunable. Theircombination with electrochemical activation enables the controlledgeneration of low-valent metal species, carbon-centered radicals,metal-germyl intermediates, or nucleophilic germanium species, dependingon the catalyst and electrochemical regime. This mechanistic flexibilityprovides opportunities to construct C–Ge bonds without theprior preparation of organogermanium nucleophiles.</p><p>In this Account,we describe our efforts to establish chlorogermane-basedelectrochemical germylation as a modular platform for C(sp<sup>3</sup>)–Ge, C(sp<sup>2</sup>)–Ge, and C(sp)–Ge bondformation, as well as for multicomponent group 14 functionalization.Cobalt electrocatalysis enables the cross-electrophile coupling ofchlorogermanes with alkyl, aryl, and alkenyl halides, providing accessto alkyl-, aryl-, and alkenylgermanes under mild conditions. Nickelelectrocatalysis extends this strategy to regioselective allylic substitutionand three-component difunctionalization of 1,3-enynes. Iron electrocatalysisenables the coupling of alkynyl chlorides with chlorogermanes, furnishingstructurally diverse alkynylgermanes while suppressing competing homocoupling.We also discuss switchable transformations of nitrile-containing substrates,in which changes in electrochemical conditions and catalyst participationresult in either decyanative germylation or anodic C–H germylation.</p><p>Mechanistic studies involving cyclic voltammetry, radical-probeexperiments, electrolysis controls, and density functional theorycalculations reveal several recurring design principles. These includecatalyst-centered reduction before direct substrate reduction, selectiveactivation of Ge–Cl and C–X bonds, controlled interceptionof carbon-centered radicals, and electrochemical modulation of radical,organometallic, and radical–polar pathways. Rather than proceedingthrough a single universal catalytic cycle, these transformationsoperate through distinct but related mechanistic pathways that canbe selected and adj","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 21","pages":"3654–3667"},"PeriodicalIF":18.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151936","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–Ligand Coordination Nanomaterials Tailored to the Cancer-Immunity Cycle","authors":"Peng Bao,&nbsp;Bei Li,&nbsp;Yunlu Dai","doi":"10.1021/acs.accounts.6c00430","DOIUrl":"10.1021/acs.accounts.6c00430","url":null,"abstract":"<p>The successful implementation of antitumor immunityhinges largelyon a chain of stepwise events known as the cancer-immunity cycle (CIC).In this cycle, tumor cell death caused by T lymphocytes triggers inflammatoryrounds of antigen-presenting cell (APC)-mediated antigen presentationand T-cell stimulation, sustaining active tumoricidal immunity, whereastumor immunosuppressive networks impose multifaceted detrimental effectson essential elements involved in the CIC, which are considered therapeutictargets for improved tumor immunotherapy. Tremendous evidence hasthrown light on the pivotal roles of metal ions in oncology, especiallyin antitumor immunity. Metal ions participate in modulating the step-by-stepevents occurring in the CIC, principally via their structural, catalytic,or modulatory interactions with immunosensors, ion transporters, anddownstream effectors, as exemplified by Mn²⁺ that sensitizescyclic GMP–AMP synthase and the stimulator of interferon genespathway to trigger antitumor T-cell immunity. Owing to their lackof targeting ability, metal ions used alone cannot serve as immunotherapeutics.Inspired by the excellent targeting properties of nanomedicines andthe unique ability of metal ions to self-assemble with diverse functionalligands, recent decades have witnessed rapid advances in metal–ligandcoordination nanomaterials for enhanced tumor immunotherapy. Unlikeother nanomedicines, metal coordination complexes can serve as multifunctionalimmunotherapeutic platforms, due to their chemical tunability anddesign versatility. Their unique composition and structure allow themto exhibit substantial outstanding properties, blazing the promisingtrail of tumor immunotherapy.</p><p>In this Account, we summarizeour recent breakthroughs in the developmentof metal–ligand coordination nanomedicines, especially in thetherapeutic mechanisms tailored for CIC, with the ultimate purposeof ameliorative cancer immunotherapy. These promising nanomedicinesare designed on the basis of stepwise events within the CIC, in whichthe targets can be subdivided into (1) tumor cells, (2) APCs, and(3) T cells. Once targeted to tumor cells, these nanomaterials generallyinduce immunogenic tumor cell death, leading to the release of numerousdanger-associated molecular patterns that exert immune-stimulatingeffects on the APCs. Metal coordination complexes also directly activateAPCs by the intrinsic immunostimulatory properties of metal ions orby delivering other adjuvants. Both pathways promote APC activationand antigen presentation for the subsequent priming of antitumor T-cellresponses. Apart from indirect APC-to-T immunostimulatory pathways,these nanomedicines directly act on T cells and reinforce their antitumorfunctions, including activation, trafficking, infiltration, and tumor-killingcapabilities. In addition, both future challenges and the anticipateddevelopment blueprint of these medicines as clinical therapeuticsare emphasized.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 21","pages":"3591–3605"},"PeriodicalIF":18.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226112","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":"Enantioselective Reactions of Palladium Enolate Intermediates: Beyond Allylic Alkylation","authors":"Christian Santiago Strong,&nbsp;Peng-Jui Chen,&nbsp;Alexander Q. Cusumano,&nbsp;William A. Goddard, III,&nbsp;Brian M. Stoltz","doi":"10.1021/acs.accounts.6c00544","DOIUrl":"10.1021/acs.accounts.6c00544","url":null,"abstract":"<p>The enantioselective Pd-catalyzedallylic alkylation reaction hasproven to be an incredibly powerful and versatile methodology forthe construction of stereoenriched building blocks bearing all-carbonquaternary centers. We have contributed to this field by investigatingthe application of chiral phosphinooxazoline (PHOX) palladium catalystsin the context of asymmetric alkylations of unstabilized nucleophilestoward a diverse array of products. In the course of our computationaland mechanistic investigations, we have uncovered an oxygen-boundPd enolate intermediate that is proposed to undergo an inner-spherepericyclic reductive elimination. This mechanistic hypothesis standsin contrast to the outer-sphere and charge-separated mechanisms proposedfor many other Pd-catalyzed allylic alkylation reactions. Interceptingthis chiral enolate with other electrophiles beyond an allyl groupwould allow more diverse chemical space to be accessible using thisplatform. This Account describes several distinct approaches towardthis end that are enabled by joint computational and experimentalmechanistic studies.</p><p>To begin, we discuss our early effortsto intercept Pd enolatesusing exogeneous electrophiles such as acidic protons and benzylidenemalononitriles. Through these approaches, we discovered that stronglyactivated and polarized external electrophiles were the most successfulsubstrates in the context of selective asymmetric transformations.We have expanded this scope to weaker carbon electrophiles by intramolecularlytethering these groups to our Pd enolate precursors alongside theapplication of exogeneous allyl scavengers. These strategies allowthe formation of products that do not bear an allyl substituent. Thisdevelopment enabled construction of a library of chiral spirocycles,motifs that are prevalent in bioactive molecules. In order to extendthe range of electrophiles compatible with this chemistry, we haveidentified the use of terminally substituted allyl groups to be importantfor the formation of stereotriads and -tetrads. Exploring these reactionsexperimentally and computationally has suggested new possible turnovermechanisms and stereochemical considerations that have informed furtherdesign iterations.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 21","pages":"3631–3641"},"PeriodicalIF":18.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149210402","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":"Proximity-Activated Photocatalytic Pharmacology: From Subcellular Compartments to Neural Circuits","authors":"Haipeng Zhang,&nbsp;Xiuyu Wang,&nbsp;Tian-Le Xu,&nbsp;Yiyun Chen","doi":"10.1021/acs.accounts.6c00470","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00470","url":null,"abstract":"&lt;p&gt;Spatialprecision of endogenous biological signalingis dictatedby submicrometer microdomains. Traditional pharmacological modalitieslack spatial resolution needed to interrogate discrete coordinates,whereas genetic methods often lack rapid kinetic control needed tocapture dynamic signaling networks. While photochemical tools offernoninvasive, spatiotemporally resolved control, their biological translationis limited by UV phototoxicity, nonspecific ROS damage, and the difficultyto achieve true subcellular localization.&lt;/p&gt;&lt;p&gt;We summarize our developmentof proximity-activated photocatalyticpharmacology via spatially confined small-molecule release, focusingon mechanistic evolution of biocompatible, metal-free photocatalyticdeboronative hydroxylation of organoboronates. We present a paradigmwhere reaction fidelity is governed not by intrinsic photochemicalproperties of substrates but by physical coordinates of the localizedphotocatalyst and short-lived reactive species generated within definedspatial boundaries. This platform operates through localized generationof transient intermediates, specifically superoxide anions (O&lt;sub&gt;2&lt;/sub&gt;&lt;sup&gt;·–&lt;/sup&gt;) and H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;,whose intracellular diffusion is constrained by native cellular quenchingmachinery. By exploiting steep concentration gradients of species,we establish a high-resolution reaction sphere for photocatalyticbond cleavage to enable precise interrogation of biological microdomains.&lt;/p&gt;&lt;p&gt;Our research program progressed through three distinct generationsto span increasingly complex biological scales:&lt;/p&gt;&lt;p&gt;• Firstgeneration (cellular scale): We established a visible-light-drivensmall-molecule release system using biocompatible organic xanthenedyes and physiological ascorbates. Operating through a single-electrontransfer pathway, this manifold selectively reduces molecular oxygento O&lt;sub&gt;2&lt;/sub&gt;&lt;sup&gt;·–&lt;/sup&gt; to drive bioorthogonal deboronativehydroxylation while bypassing cytotoxic energy transfer pathways.&lt;/p&gt;&lt;p&gt;• Second generation (subcellular scale): We achieved subcellularprecision by engineering targeted chemical scaffolds and hybrid geneticallytargeted platforms (e.g., SNAP-FL) to restrict photocatalytic activityto specific organelle coordinates. By advancing to fully geneticallyencoded 12 kDa miniature photoenzymes (miniSOG), we eliminated exogenouschemical catalyst requirements. Together, these methods enabled usto map compartment-specific drug toxicities, drive selective mitochondrialdepolarization, and achieve nucleus-specific epitranscriptomic remodelingof m&lt;sup&gt;6&lt;/sup&gt;A RNA methylation.&lt;/p&gt;&lt;p&gt;• Third generation(circuit scale): We deployed these platformsto decipher complex architecture of the mammalian nervous system.By expressing membrane-anchored SNAP-FL at projection-specific synapticterminals, we achieved optochemical neuromodulation in acute brainslices within seconds. Ultimately, this enabled cell-type-specificphotocatalytic pharmacology &lt;em&gt;in vivo&lt;/em&gt;, facil","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 21","pages":"3606–3618"},"PeriodicalIF":18.0,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305698","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":"Electrochemically Generated Platform Oxidizers: An Enabler for the Hydrogen Economy","authors":"Darryl F. Nater,Finn Moeller,Aloisio de A. Bartolomeu,Felix M. Fuchs,Ziqi Teng,Siegfried R. Waldvogel","doi":"10.1021/acs.accounts.6c00614","DOIUrl":"https://doi.org/10.1021/acs.accounts.6c00614","url":null,"abstract":"A highly attractive alternative anode reaction for electrochemical hydrogen production is the formation of platform oxidizers instead of molecular oxygen. These platform oxidants are high-value products and can therefore help cofinance hydrogen production. For most electro-organic reactions, the electrochemical conditions for hydrogen production would be incompatible, due to the high current density required, whereas the anodic production of platform oxidizers demonstrates technical complementarity. The broad range of applications for such platform oxidants and versatility allow for broad applications and large-scale use, including the synthesis of complex, high-value target products. For platform oxidizing agents that utilize elements that are in limited supply or pose environmental concerns, a closed-loop system must be established between their production and recycling. The recovery and regeneration of reaction waste into platform oxidizing agents must ensure that no cross-contamination occurs during the production of the target products and that these platform oxidizing agents can be transported and stored safely. Among many other platform oxidants, periodates and peroxodicarbonates are the most promising. This is because either a wide range of applications is already known, or the resulting byproducts serve as critical reactants for processes involving biogenic feedstock. Periodates have also been demonstrated to work in a closed-loop system: if these platform oxidants are used on-site, much simpler and easier-to-store starting compounds can be used, which then yield harmless coproducts that do not need to be recovered, e.g., alkali carbonates. In most cases, these platform oxidizers can be produced in an undivided electrolytic cell. This improves the energetics of the electrolytic reaction. The anodic reaction typically occurs at electrodes with a high overpotential for the oxygen-evolution reaction. Due to the temporary storage of the platform oxidants, this approach can contribute efficiently to the transformation of the chemical industry, as it allows safe hydrogen generation on demand and is tailored to the electricity supply.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"48 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149305301","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}