Accounts of Chemical Research最新文献

{"title":"Addressing Clinical Challenges of Platinum Anticancer Drugs through Rational Chemical Design","authors":"Shuren Zhang,&nbsp;Zijian Guo","doi":"10.1021/acs.accounts.6c00342","DOIUrl":"10.1021/acs.accounts.6c00342","url":null,"abstract":"<p>Platinum (Pt)-based anticancerdrugs have been a cornerstone ofchemotherapy for decades, yet their clinical application remains constrainedby dose-limiting systemic toxicity and drug resistance. In this Account,we summarize our systematic efforts to address these challenges throughtwo complementary strategies: 1) functionalization of Pt(IV) prodrugsand 2) spatially controlled targeted delivery. The kinetic inertnessand octahedral geometry of Pt(IV) complexes offer a versatile platformfor axial functionalization, allowing the integration of diverse bioactiveligands that are released upon intracellular reduction. Exploitingthis feature, we have developed multifunctional Pt(IV) prodrugs thatco-target DNA damage repair and apoptotic pathways, rewire cholesteroland energy metabolism, induce nonapoptotic cell death including PANoptosisand autophagy-associated death, and epigenetically silence resistance-associatedgene networks via chromatin compaction. To engage the tumor immunemicroenvironment, we have incorporated immunomodulators─includingSTING agonists, TREM2/CD33 inhibitors, and STAT3 blockers─toamplify innate and adaptive antitumor immunity. Furthermore, we havedeveloped radiotherapy-responsive Pt(IV) prodrugs that undergo rapid,X-ray-triggered reduction mediated by hydrated electrons, enablingspatiotemporally precise drug activation with markedly attenuatedsystemic toxicity. This strategy is currently advancing toward clinicaltranslation through IND-enabling studies. In parallel, we have establishedtargeted delivery platforms to improve the spatial precision of Ptagents. Mitochondria-targeted complexes redirect cytotoxicity to anorganelle lacking efficient DNA repair, disrupting bioenergetics andtriggering intrinsic apoptosis. At the tissue level, biotin-mediatedtargeting exploits overexpressed vitamin transporters for tumor-selectiveaccumulation, while Pt(IV)–antibody conjugates (Pt-ADCs) achieveantigen-specific delivery, upregulate tumor MHC-I expression, expandTCR clonotypes, and synergize with PD-1 blockade. Additionally, astimuli-responsive in situ self-assembly strategy enables enzyme-triggerednanostructure formation and intracellular disassembly for enhancedtumor accumulation and burst drug release. An immunocompetent patient-derivedorganoid platform has been established to screen these agents in aclinically relevant setting. The integration of multifunctional modulation,targeted delivery, and externally controlled activation within singlePt-based systems creates a synergistic framework that simultaneouslyaddresses resistance and toxicity. Moving forward, our research willfocus on optimizing pharmaceutical properties, advancing radiotherapy-responsivePt(IV) prodrugs and Pt-ADCs toward clinical evaluation, and refiningpredictive screening platforms. These programmable Pt therapeuticshold considerable promise for delivering safer and more effectiveprecision chemotherapy to cancer patients.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2438–2449"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416546","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":"Selectivity by the Clock: Programming Reactivity with Alternating Current Frequency","authors":"Diptangshu Datta Mal,&nbsp;Nibedita Behara,&nbsp;Long Luo","doi":"10.1021/acs.accounts.6c00439","DOIUrl":"10.1021/acs.accounts.6c00439","url":null,"abstract":"&lt;p&gt;Electrochemical reactions areinherently programmable through theapplied potential. However, conventional direct current (DC) electrolysisprovides only limited control over reaction selectivity because itgenerates a static redox environment in which substrates and intermediatesremain continuously exposed to either oxidizing or reducing conditions.As a result, reactive intermediates often undergo undesired overoxidation,overreduction, or competing side reactions. Alternating current (AC)electrolysis overcomes these limitations by periodically reversingelectrode potential polarity, creating a dynamic redox environmentin which oxidation and reduction can be regulated in the time domain.In addition to potential, AC electrolysis introduces frequency asa new experimental parameter for controlling reaction pathways. Inthis Account, we highlight our group’s recent efforts to understandhow AC frequency controls reaction selectivity. We show that AC frequencyserves as a kinetic synchronization parameter, matching electrochemicaltime scales to the rates of key chemical steps. By controlling theduration that reactive intermediates experience oxidizing or reducingenvironments, AC electrolysis enables selective access to reactionpathways that are difficult or impossible to achieve under conventionalDC conditions. Using representative examples, we illustrate severalmechanistic modes through which AC frequency governs reaction outcomes.First, we demonstrate that frequency-controlled modulation of theredox environment can distinguish between one- and two-electron oxidationpathways of amines, enabling the selective generation of α-aminoradicals while suppressing the formation of iminium ions. This principlewas further extended to electrochemical hydrogen isotope exchange,in which AC frequency synchronizes proton transfer and hydrogen atomtransfer to achieve efficient, site-selective isotope incorporation.Second, we show that AC frequency can synchronize with homogeneouscatalytic cycles. In a Ni-catalyzed C–N cross-coupling reaction,the optimal frequency arises from matching the AC waveform to theformation rate of a key Ni(II) catalytic resting state. Third, wedemonstrate that AC electrolysis can dynamically maintain catalyticallyactive electrode structures and alter chemical speciation in heterogeneouselectrocatalysis. In an industrial Ag-catalyzed dehalogenation process,AC electrolysis continuously regenerates a defect-rich Ag catalystwhile suppressing chlorine-mediated decomposition pathways, leadingto dramatically improved long term selectivity and catalyst stability.We further describe our efforts to establish finite-element modelingapproaches for AC electrolysis. Using the AC-enabled partial reductionof (hetero)arenes as a model system, we show how electrochemical kineticsextracted from cyclic voltammetry can be integrated with finite-elementsimulations to reproduce experimental selectivity trends and identifythe kinetic criteria required for selective par","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2587–2599"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148546933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Light-Driven Oxidation of Light Alkanes: Current Challenges and Prospects","authors":"Yong Xu","doi":"10.1021/acs.accounts.6c00286","DOIUrl":"10.1021/acs.accounts.6c00286","url":null,"abstract":"<p>The current energy crisis andenvironmental concerns inspire researchersto develop new strategies to reinvent the conventional oil-based energysystem. Shale gas, a mixture of light alkanes including methane, ethane,propane, and butane, can serve as an alternative to oil for producingvalue-added chemicals. Nevertheless, the conventional conversion oflight alkanes requires high temperature due to the chemical inertnessof C–H bond, which suffers from intensive energy consumptionand challenges including the control of target product’s selectivityand the long-term stability of catalyst. Addressing these challengesdemands the innovation of sustainable catalytic systems with a goodbalance of activity, selectivity, and stability. Photocatalysis hasrecently attracted great interest in industry since it can harvestsolar energy to trigger C–H activation at room temperature,being a clean method for the oxidation of light alkanes. Over pastdecades, great efforts have been devoted to the light-driven oxidationof light alkanes. Nevertheless, light-driven processes are limitedby disadvantages including low productivity, tricky photon–electron–phononinteractions, and ultraviolet light dependence, which restrict theirpractical applications. Our group has contributed a series of advancesin the light-driven oxidation of methane, ethane and propane to value-addedchemicals via the precise control of interfacial structures of photocatalysts.This Account mainly focuses on the three key dimensions: (i) photothermal-inducedoxidation of light alkanes, (ii) photocatalytic oxidation of lightalkanes, and (iii) integrating photothermal-photocatalysis for theoxidation of light alkanes. It also confronts the current challengesin this field and proposes feasible strategies for addressing thoseissues. Although various products have been obtained via light-drivenoxidation of methane at room temperature, future investigations shouldbe closely oriented toward practical application. In this regard,special attention should be paid to the following aspects: (i) enhancingthe utilization of visible and near-infrared light, (ii) balancingthe correlation of activity–selectivity–-stability,and (iii) investigating light-driven oxidation of ethane, propane,and butane.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2365–2375"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432631","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":"Advanced Oxidation Processes for Precious Metal Recycling","authors":"Anting Ding,&nbsp;Wen Liu,&nbsp;Zhenfeng Bian,&nbsp;Chengliang Xiao","doi":"10.1021/acs.accounts.6c00314","DOIUrl":"10.1021/acs.accounts.6c00314","url":null,"abstract":"&lt;p&gt;Precious metals, including Au,Ag, Pt, Pd, and Rh, are indispensableto modern catalysis, electronics, and emerging energy technologies,yet their scarcity and geographical supply chain vulnerabilities posesignificant supply risks. At the same time, the rapid growth of electronicwaste and spent catalysts has created a paradoxical situation in whichprimary resources remain constrained but secondary resources increasinglycontain precious metal concentrations that match or even exceed thoseof natural ores. This tension has made precious metal recycling botha strategic necessity and a scientific challenge. Despite substantialprogress in hydrometallurgy, the field remains heavily dependent onharsh leaching systems such as aqua regia and cyanidation, which sufferfrom poor selectivity, corrosive conditions, toxic reagents, and secondaryenvironmental burdens. The central challenge is unchanged: chemicallyinert precious metals must first be oxidized into soluble speciesbefore downstream separation and purification can occur.&lt;/p&gt;&lt;p&gt;Ourwork has approached this longstanding problem from a differentperspective. Rather than relying on increasingly harsh reagents, wehave begun to view precious metal dissolution as a controllable oxidationprocess that can be re-engineered through advanced oxidation processes.This shift has opened a new conceptual framework in which reactiveoxygen species are deliberately harnessed to oxidize precious metalsunder substantially milder conditions. Within this emerging area,advanced oxidation is not simply borrowed from environmental catalysisfor the degradation of pollutants; it is being redefined as a distinctmethodological paradigm for precious metal metallurgy.&lt;/p&gt;&lt;p&gt;In thisAccount, we summarize how this idea has evolved acrossseveral complementary platforms. We first discuss photocatalytic andpiezocatalytic systems, where light or mechanical stimulation drivesthe formation of reactive species and solvent-derived ligands formetal dissolution. We then examine homogeneous persulfate-based Fenton-likesystems, which transfer oxidant activation into the bulk solutionand reveal how radical and nonradical pathways cooperate in oxidativeleaching. Next, we highlight our recent efforts in single-atom catalysis,where isolated metal sites provide a bridge between molecular-leveloxidant activation and heterogeneous robustness, enabling rapid andselective precious metal recovery with improved catalyst recyclability.Finally, we discuss self-catalytic leaching, an especially streamlinedlimit in which the precious metal itself participates in generatingthe oxidizing species required for its own dissolution.&lt;/p&gt;&lt;p&gt;Together,these studies suggest that the future of precious metalrecycling will be defined not solely by stronger oxidants but alsoby the rational integration of oxidative power, ligand coordination,interfacial control, and process sustainability. By tracing this developmentfrom fundamental mechanisms to scalable recovery strategies, thi","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2412–2424"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428831","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":"Decade of Discovery: The Evolution and Future of Laser-Scribed Graphene for Integrated Energy and Sensing Systems","authors":"Zhiyin Yang,&nbsp;Cheng-Wei Lin,&nbsp;Richard B. Kaner","doi":"10.1021/acs.accounts.6c00363","DOIUrl":"10.1021/acs.accounts.6c00363","url":null,"abstract":"<p>The widespread adoption of graphenein commercial technology haslong been hindered by the difficulty of producing high-quality materialat scale and patterning it into functional circuits without complex,multistep lithography. This Account explores our laboratory’ssolution to this challenge: the photothermal transformation of solution-processablegraphene oxide (GO) into laser-scribed graphene (LSG). Unlike pristinegraphene, which is difficult to disperse and pattern, GO is easilysynthesized from bulk graphite and can be cast into uniform filmson virtually any substrate via scalable solution-processing techniques.</p><p>The transition from GO to LSG is significantly simplified throughthe use of a standard CO₂ laser source. We observed thatlaser-scribed GO areas undergo highly effective reduction, characterizedby a rapid expansion and exfoliation of the layers. This results ina film with exceptional conductivity and high porosity, yielding aremarkable surface area of 1520 m² g^–1. This reduction process fundamentally alters the chemical compositionof the film, shifting it to a carbon content of 96.5% with a residualoxygen content of only 3.5%.</p><p>Beyond pure carbon architectures,the core of our recent researchfocuses on the chemical diversification of the LSG library. Afterthe first finding of laser-scribed graphene for supercapacitors, wefound that by utilizing GO as a versatile host matrix, we have demonstratedthat functional additives can be seamlessly integrated into the 3Dgraphene network during the scribing process. This Account will highlightour work from pure laser-scribed graphene to various materials withLSG as a host matrix, including laser-assisted lattice recovery ofgraphene by carbon nanodot incorporation, Si/LSG composites for high-capacitylithium-ion anodes, and the incorporation of VCl₃ to createmultivalent vanadium oxide/graphene hybrids for advanced sodium-ionbatteries.</p><p>These hybrid materials allow for precise tuning ofthe electrochemicaland electronic properties of the resulting devices. We will detailhow this laser-scribe approach enables the integration of these materialsinto multifunctional electronic systems. By bridging the gap betweenmolecular-level carbon chemistry, heteroatom doping, and roll-to-rollmanufacturing, LSG provides a blueprint for the future of wearableelectronics and sustainable, integrated energy systems.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2474–2486"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498893","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":"Carbon Dots for Electroluminescence: Bridging Molecular Fluorophores and Quantum Emitters","authors":"Qian Teng,&nbsp;Chenhao Li,&nbsp;Qinghua Tan,&nbsp;Yuxin Shi,&nbsp;Fanglong Yuan","doi":"10.1021/acs.accounts.6c00385","DOIUrl":"10.1021/acs.accounts.6c00385","url":null,"abstract":"&lt;p&gt;Carbon dots (CDs) are an emerging class of carbon-basedluminescentnanomaterials composed of localized sp&lt;sup&gt;2&lt;/sup&gt;-conjugated domainsand edge/surface functional groups. Unlike inorganic quantum dots,CDs are constructed from earth-abundant, low-toxicity elements andcan be chemically programmed through precursor design, heteroatomincorporation, edge-state regulation, and topology engineering. Atthe same time, unlike molecular fluorophores, CDs are nanoscale condensed-stateemitters whose optical properties are governed by quantum confinement,chemical composition, aggregation, interdomain coupling, and solid-stateorganization. CDs therefore occupy a unique position between molecularemitters and semiconductor quantum dots. This hybrid identity becomesparticularly important in light-emitting diodes (LEDs), where electroluminescencearises not from intrinsic photophysical properties alone but fromthe coupled interplay of charge injection, carrier transport, excitonconfinement. As a result, electroluminescent performance cannot bedirectly inferred from solution-phase photoluminescence. This distinctionis especially critical for CDs, whose emissive states are highly sensitiveto condensed-state packing, interfacial interactions, and device architecture,often leading to a disparity between photoluminescence efficiencyand electroluminescent performance. Within this context, we show thatCDs offer unique opportunities for electroluminescent applicationswhile also presenting fundamental challenges. Their emission is highlytunable through structural and chemical design, enabling broad spectralcontrol across the visible region. Their carbon-based compositionprovides a heavy-metal-free alternative to Cd- and Pb-based emitters,and their solution processability supports scalable thin-film fabrication.However, conventional CDs suffer from broad emission bandwidths, structuralheterogeneity, aggregation-induced quenching, and fluorescence-dominatedexciton utilization, which limit efficiency and color purity. We identifythat recent progress lies not only in achieving electroluminescence,but in transforming CDs into increasingly programmable emissive systems.&lt;/p&gt;&lt;p&gt;In this Account, we present the evolution of CD-based electroluminescentmaterials from the perspective of coupled structure–photophysics–devicerelationships. We first establish the device framework of CD-LEDs,including multilayer architectures, energy-level alignment, and therole of the emissive layer in charge recombination and exciton relaxation.We then discuss synthetic strategies that advance CD emitters fromempirically carbonized products toward increasingly structure-definedsystems. On this basis, we highlight four key directions: multicolorelectroluminescence via hierarchical emissive-state regulation, narrowbandemission through molecular programming, efficient solid-state emission,and triplet-exciton management. Together, we demonstrate that theseadvances establish CDs as a class of programmable el","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2548–2560"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432798","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":"Formal Hydride Abstraction: A Unified Photoredox Platform for Nucleophilic C(sp3)–H Functionalization","authors":"James Mortimer,&nbsp;Patricia Z. Musacchio","doi":"10.1021/acs.accounts.6c00378","DOIUrl":"10.1021/acs.accounts.6c00378","url":null,"abstract":"<p>Carbocations are among the most versatile reactiveintermediatesin organic synthesis. Serving as the electrophilic linchpin for fundamentaltransformations such as S_N1 substitutions, Friedel–Craftsalkylations, Ritter reactions, polyene cyclization cascades, and manyother transformations, they provide a powerful means to constructC–C and C–heteroatom bonds. Classically, however, accessto these high-energy intermediates has been restricted to the ionizationof reactive precursors ─ alkyl halides or sulfonates ─often requiring harsh thermal, acidic and/or solvolytic conditionsthat limit functional group tolerance and favor competitive elimination.The ability to generate carbocations directly from ubiquitous, inertC(sp³)–H bonds has long been considered a holy grailof chemical synthesis. Otherwise known as hydride abstraction, itis hampered by a steep thermodynamic barrier; the heterolytic cleavageof a C–H bond is significantly more endergonic than its homolyticcounterpart.</p><p>This Account describes our laboratory’sdevelopment of acatalytic platform that overcomes this thermodynamic challenge toenable a general formal hydride abstraction. We reasoned that thehigh-energy process of removing a hydride (H^–) ina single step could be decoupled into two lower-energy, kineticallyaccessible steps mediated by visible-light photoredox catalysis: HydrogenAtom Transfer (HAT) followed by oxidative Radical-Polar Crossover(RPC), or [HAT+RPC]. By utilizing a photocatalyst to orchestrate boththe generation of a carbon-centered radical and its subsequent oxidationto a carbocation, we have unlocked a manifold for S_N1-typereactivity on simple hydrocarbons under mild conditions.</p><p>Wetrace the evolution of this concept from its genesis in nucleophilicC–H fluorination, where we utilized <em>tert</em>-butylperoxybenzoate (TBPB) to engage the fluoride anion ─ a classicallydifficult coupling partner in homolytic transformations. Buildingon this success, we expanded the platform to oxygen nucleophiles,establishing a photochemical alternative to the Williamson ether synthesisthat avoids the elimination side-reactions typical of strong bases.We further detail the critical reagent evolution necessitated by nitrogennucleophiles, where the introduction of <em>N</em>-alkoxypyridiniumsalts solved the problem of competitive byproduct nucleophilicity,enabling the synthesis of <em>N</em>-benzyl azoles. Finally,we discuss our deep mechanistic interrogation of C–H sulfonamidation,where the identification and suppression of a parasitic proton-coupledelectron transfer (PCET) pathway proved essential for catalytic efficiency.</p><p>Collectively, these studies demonstrate that with the correct polarity-inversionmachinery, C–H bonds can be viewed not merely as radical precursors,but as latent carbocations ready to engage in the full spectrum ofpolar reactivity.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2538–2547"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589138","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-Centered Photoredox Catalysis using d6 Transition Metal-based Chromophores","authors":"Micheal M. Alowakennu,&nbsp;Bekah E. Bowers,&nbsp;Björn Pfund,&nbsp;James K. McCusker","doi":"10.1021/acs.accounts.6c00326","DOIUrl":"10.1021/acs.accounts.6c00326","url":null,"abstract":"&lt;p&gt;Controlling excited-state reactivityin transition metal chromophoresis central to light-driven chemistry, with applications spanning fromsolar energy conversion to photoredox catalysis. Ru(II) and Ir(III)chromophores currently dominate applications within this field dueto their long-lived charge-transfer (CT) excited states, which supportbimolecular electron transfer chemistry. However, their elementalscarcity and relative lack of selectivity for differentiating oxidativeversus reductive pathways has in part motivated the exploration ofalternative platforms that could, in principle, offer distinct mechanisticopportunities.&lt;/p&gt;&lt;p&gt;Earth-abundant, valence-isoelectronic 3d&lt;sup&gt;6&lt;/sup&gt; complexesof Fe(II) and Co(III) have attracted significant attention due totheir electronic similarity to Ru(II) and Ir(III), suggesting thepotential for complementary photophysical behavior. In contrast totheir heavier congeners, however, the weaker ligand fields of first-rowtransition metals promote rapid relaxation from initially populatedCT states to low-lying metal-centered (MC) excited states, typicallyof &lt;sup&gt;5&lt;/sup&gt;T&lt;sub&gt;2&lt;/sub&gt; or &lt;sup&gt;3&lt;/sup&gt;T&lt;sub&gt;1&lt;/sub&gt; character.Because these MC states involve redistribution of electron densitywithin MC d-orbitals rather than charge separation between metal andligand orbitals, they were historically considered poor candidatesfor use in photochemical transformations.&lt;/p&gt;&lt;p&gt;In this Account, wesummarize our and others’ recent workthat challenges this paradigm by establishing MC excited states inFe(II) and Co(III) complexes as distinct and mechanistically powerfulplatforms for productive photochemistry. We begin by outlining howthe nature of the reactive MC excited state can be identified andhow its spin-state character impacts photochemical reactivity. Thisis important because MC excited states are defined by complex potentialenergy landscapes in which multiple competing pathways are presentand can be profoundly different with regard to both spin state andequilibrium geometry. For Fe(II) complexes, &lt;sup&gt;5&lt;/sup&gt;T&lt;sub&gt;2&lt;/sub&gt; excited states are unreactive in photoredox processes due to substantialreorganization energy and limited access to low-spin Fe(III) products.In contrast, &lt;sup&gt;3&lt;/sup&gt;T&lt;sub&gt;1&lt;/sub&gt; excited states of Fe(II) andCo(III) enable productive electron-transfer pathways by minimizingspin and structural reorganization, providing access to Fe(III) andCo(II) products under favorable conditions. These insights establishkey design principles for tuning reactivity through ligand field strengthand excited-state electronic structure.&lt;/p&gt;&lt;p&gt;Together, these findingsestablish MC excited states as a fundamentallydistinct platform for photoredox catalysis with advantages –including enhanced selectivity – that can be leveraged in waysdifficult, if not impossible, to realize in conventional CT-basedsystems. More broadly, this work has allowed for the development ofdesign rules for exploiting MC excited states of earth-abundant,","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2462–2473"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428764","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":"Why Single-Atom Alloys (SAAs) Outperform Their Individual Metal Components in Catalysis","authors":"Francisco Zaera","doi":"10.1021/acs.accounts.6c00375","DOIUrl":"10.1021/acs.accounts.6c00375","url":null,"abstract":"&lt;p&gt;Much industrial catalysis employsnoble metals such as Pt, Pd,and Rh to facilitate the activation of key diatomic reactants suchas H&lt;sub&gt;2&lt;/sub&gt; and O&lt;sub&gt;2&lt;/sub&gt;, a requisite for the promotionof hydrogenation and oxidation reactions, respectively. However, thesemetals are often unselective for the conversion of organic feedstocks,so the addition of another, moderating metal is usually needed. Theresulting bimetallics have gained prominence recently with an emphasison so-called single-atom alloys (SAAs), in which the active component(the guest; Pt, Pd) is highly diluted within a matrix of a mildersecond metal (the host; Cu, Au, Ag). Empirically, SAAs have been shownto improve the selectivity of many catalytic reactions, but a fullexplanation of how this occurs is still lacking. A simple model hasbeen advanced, based on “modern surface-science” studiesusing model surfaces under ultrahigh vacuum (UHV), where the guestatoms are isolated on the surface of the host and are presumed tonot be significantly affected by it. They are proposed to promotethe activation of the diatomic molecule (H&lt;sub&gt;2&lt;/sub&gt;, O&lt;sub&gt;2&lt;/sub&gt;), after which the resulting atoms (H, O) spill over onto the hostsurface where the rest of the catalytic conversion takes place. Unfortunately,this mechanism fails to explain certain observations from studiesof SAAs under catalytic conditions, where the metals exist as nanoparticles(NPs) dispersed on high-surface-area supports, typically porous oxides,and where the surfaces are exposed to atmospheric pressures of thereactants. Our studies have focused on bridging these &lt;em&gt;materials&lt;/em&gt; and &lt;em&gt;pressure&lt;/em&gt; gaps, using the selective hydrogenationof unsaturated aldehydes with Pt–Cu alloys as a prototypicalsystem. We have determined that, in the very dilute limit, the Ptatoms are located not on the exposed NP surface but rather at theinterface between the metal NP and the oxide support, where they areinaccessible to the reactants. Furthermore, their effect on catalyticperformance was found to be indirect, via the remote modificationof the electronic properties of the surface Cu atoms where the reactionstake place. Specifically, the activation barrier for molecular hydrogendissociation at the Cu sites is decreased, thereby facilitating theproduction of the atomic hydrogen required for the hydrogenation ofthe organic adsorbates. Moreover, the added Pt modifies both the adsorptionmode and the energetics of the reactants and products on Cu sitesand the rate constants of the hydrogenation steps; like pure Cu onceit is provided with atomic hydrogen, the Cu–Pt SAAs enhancethe production of the desired products (unsaturated alcohols fromunsaturated aldehydes), likely by favoring a unique reactant adsorptiongeometry through the oxygen atom. Our findings contradict the proposedindependence of the two metals that constitutes the essence of thecurrent working model for SAA and provide a new explanation of howSAAs function that may lead to better for","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2516–2523"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589197","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 Programming of Intratumoral Boron for Boron Neutron Capture Therapy","authors":"Sanoj Rejinold N,&nbsp;Goeun Choi,&nbsp;Koji Ono,&nbsp;Hiroyuki Nakamura,&nbsp;Jin-Ho Choy","doi":"10.1021/acs.accounts.6c00253","DOIUrl":"10.1021/acs.accounts.6c00253","url":null,"abstract":"&lt;p&gt;Boron neutron capture therapy(BNCT) is a radiotherapeutic modalityin which biological selectivity is dictated not by targeting alonebut by the spatial control of nuclear reactions. Following tumor-selectiveaccumulation of &lt;sup&gt;10&lt;/sup&gt;B, neutron irradiation induces the &lt;sup&gt;10&lt;/sup&gt;B(n,α)&lt;sup&gt;7&lt;/sup&gt;Li reaction, generating high–linearenergy transfer particles with micrometer path lengths that confinecytotoxicity to boron-enriched cells. Despite its intrinsic precision,the clinical translation of BNCT has long been hindered by a fundamentalchemical challenge: the inability to achieve sufficient, homogeneous,and durable intratumoral boron distribution. In this Account, we arguethat BNCT must be reframed as a problem of chemical architecture acrosslength scales, rather than a simple paradigm of boron delivery followedby irradiation. Building on foundational contributions from Jin-HoChoy (layered double hydroxide–based confinement and ion-exchangesystems), Hiroyuki Nakamura (molecular boron design enabling targetingand functional integration), and Koji Ono (clinical dosimetry andtranslational constraints), we outline how nanohybrid platforms transformBNCT into an integrated systems therapy in which materials design,biological transport, and radiation physics are co-optimized. We identifythree governing design principles for next-generation BNCT. First,structural confinement and high-density boron loading enabled by layeredinorganic hosts, carborane clusters, and hybrid nanocarriers, ensuresufficient payload delivery at the cellular and subcellular levels.Second, spatiotemporal control of boron distribution, achieved throughsurface engineering, targeting ligands, and microenvironment-responsiverelease, addresses the critical challenge of intratumoral heterogeneity.Third, integration with imaging and dosimetry establishes a “measure-what-you-treat”paradigm, linking molecular design directly to therapeutic outcome.We further highlight that BNCT efficacy is governed not by bulk tumorboron concentration alone but by microdistribution and subcellularlocalization, reflecting the short path length of high-linear energytransfer(LET) particles. This insight shifts design strategies frommaximizing systemic delivery toward controlling intracellular fateand spatial precision. In parallel, the transition to accelerator-basedneutron sources imposes additional constraints on boron chemistry,necessitating higher delivery efficiency and tighter coordinationbetween pharmacokinetics and irradiation conditions. Together, theseadvances position BNCT as a chemically programmable precision radiotherapy,in which therapeutic outcome is dictated by the hierarchical organizationof boron from molecular to nanoscale to clinical dimensions. Futureprogress will depend on scalable chemical design, quantitative imagingof boron distribution, and integration with emerging therapeutic modalities.We propose that the next phase of BNCT will be defined by the convergenceof nanochemistry","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 15","pages":"2336–2347"},"PeriodicalIF":18.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148546923","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}