JACS Au最新文献

{"title":"Probing Interfacial Electrolyte Chemistry and SEI Failure Mechanisms on Lithium-Metal Anodes via Establishing a Multichannel Analysis Paradigm","authors":"Yuan Tian,&nbsp;Wenbin Tu,&nbsp;Jiyuan Xue,&nbsp;Yuran Yang,&nbsp;Zhanpeng Xu,&nbsp;Feihong Wang,&nbsp;Xin Liu,&nbsp;Jizhong Cao,&nbsp;Jing Zeng,&nbsp;Zhengliang Gong,&nbsp;Dong Ni,&nbsp;Yeguo Zou,&nbsp;Yu Qiao,&nbsp;Shi-Gang Sun","doi":"10.1021/jacsau.6c00892","DOIUrl":"https://doi.org/10.1021/jacsau.6c00892","url":null,"abstract":"<p>The formation and failure of the solid electrolyte interphase(SEI)govern the reversibility, stability, and safety of Li metal anodes.However, the dynamic construction process of the SEI and the associatedmultiphase product evolution originating from interfacial electrolytedecomposition remain insufficiently understood. Herein, we establisha multichannel interfacial product analysis paradigm that enablesthe tracking of distinct products during electrolyte decompositionand SEI evolution across gaseous, volatile, solid, dead Li, and thermal-responsepathways. Using traditional and fluorinated carbonate electrolytesas model systems, we demonstrate that the traditional electrolyteundergoes continuous carbonate fragmentation, forming an SEI enrichedin organic and carbonate species with limited passivation capability,thereby inducing interfacial reconstruction, dead Li accumulation,and pronounced gas evolution under thermal stress. In contrast, fluorinatedelectrolytes follow a more convergent decomposition pathway to forma LiF-rich composite SEI, which reduces dead Li formation, stabilizesLi plating/stripping, and markedly suppresses the release of interfacialgases during thermal decomposition. More broadly, this integratedmultitechnique characterization system provides a powerful analyticaltool to precisely resolve SEI formation and failure processes, therebyoffering scientific insights and practical engineering strategiesfor developing safer and highly reversible Li-metal batteries.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5232–5242"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary-Amine Relay Enables Lysine-Directed Multicomponent Functionalization of Peptides","authors":"Cheng Ren,&nbsp;Mengyao Zhang,&nbsp;Tiefeng Jiang,&nbsp;Feng Wan,&nbsp;Yicheng Lv,&nbsp;Lin Yang,&nbsp;Chengxi Li","doi":"10.1021/jacsau.6c00945","DOIUrl":"https://doi.org/10.1021/jacsau.6c00945","url":null,"abstract":"<p>Multicomponent reactions provide powerful modularityfor peptidefunctionalization, but their application to lysine residues remainslimited by the low efficiency of direct primary-amine-based activationpathways under peptide-compatible conditions. Here we report a secondary-aminerelay strategy for lysine-directed multicomponent functionalizationof peptides. In this approach, salicylaldehyde derivatives, arylboronicacids, and a cyclic secondary amine are combined to generate a transientelectrophilic intermediate, which is subsequently intercepted by theε-amine of lysine-containing peptides. By separating electrophilegeneration from direct lysine activation, this relay protocol improvesthe efficiency of lysine modification while retaining the modularityof multicomponent chemistry. Mechanistic experiments, isolated intermediatestudies, kinetic comparisons, and density functional theory calculationssupport a pathway involving secondary-amine-mediated intermediateformation followed by lysine capture. The method enables modificationof diverse bioactive peptides, incorporation of drug-derived and fluorescentaldehyde or boronic acid components, and lysine–lysine staplingusing bifunctional aldehydes. The reaction is further compatible withautomated and parallel solid-phase peptide modification workflows,providing rapid access to libraries of lysine-functionalized peptideconjugates. This study provides a practical secondary-amine relayplatform for modular peptide functionalization and expands the utilityof multicomponent chemistry in automated peptide synthesis.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5264–5274"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrogen in Supramolecular Chemistry: Understanding the Pervasive Role as Acceptor of Halogen, Chalcogen, Pnictogen and Tetrel Bonds","authors":"Harry. W. Nash,&nbsp;Elna Pidcock,&nbsp;Joanna S. Stevens,&nbsp;J. Grant Hill,&nbsp;Lee Brammer","doi":"10.1021/jacsau.6c00809","DOIUrl":"https://doi.org/10.1021/jacsau.6c00809","url":null,"abstract":"<p>Nitrogen-centered Lewis bases are well established asnucleophilesin synthetic chemistry, as ligands in coordination chemistry and aspervasive components of hydrogen bonding in chemistry and structuralbiology. Their role as acceptors of halogen, chalcogen, pnictogenand tetrel bonds, collectively σ-hole interactions, is alsowell established experimentally, but only selectively investigatedthrough exploration of geometric and energetic trends. Here we reporta comprehensive study, in which we identify the prevalence of thisclass of interactions and analyze experimental geometric trends fromcrystallographic data. These analyses are supported by high-accuracycoupled-cluster quantum chemical calculations of interaction energiesand use of symmetry-adapted perturbation theory (SAPT) to examinethe underlying energetic contributions. Our focus is on comparison,across the four families of σ-hole interactions, of the behaviorfor N_sp³ vs N_sp² vs N_sp hybridization at the nitrogen atom bearing the lone pair.Halogen and chalcogen bonds are more abundant than pnictogen and tetrelbonds, whereas interaction prevalence tends to be greatest for theheavier congeners in each σ-hole donor group (i.e., I, Te, Sb/Bi,Sn/Pb). The relative prevalence of tetrel bonds compared to halogenbonds increases from N_sp³ to N_sp² to N_sp acceptors, highlighting the importance ofsteric demands. The heavier congeners among the σ-hole donorsgenerally form interactions with shorter normalized interaction distances,although this is mitigated by sterics, most prominently for tetrelbonds and for N_sp³ Lewis bases. Preference forlinearity with respect to the σ-hole angle and the angle atthe nitrogen lone pair follow the trend N_sp³ &gt; N_sp² &gt; N_sp also as a consequenceof steric demands. More generally, SAPT analysis of interaction energiesclearly indicates the prominent influence of sterics, through exchangerepulsion, on angular preferences of all interactions. The broaderimplications of these comprehensive results in areas such as supramolecular,materials and medicinal chemistry are considered.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5163–5178"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiobjective Fluorescent Molecule Design with a Data-Physics Dual-Driven Generative Framework","authors":"Yanheng Li,&nbsp;Zhichen Pu,&nbsp;Lijiang Yang,&nbsp;Yue Xue,&nbsp;Zehao Zhou,&nbsp;Yi Qin Gao","doi":"10.1021/jacsau.6c00832","DOIUrl":"https://doi.org/10.1021/jacsau.6c00832","url":null,"abstract":"<p>Designing fluorescentsmall molecules requires simultaneous controlover optical responses, brightness, and physicochemical constraintsacross vast, underexplored chemical spaces. Conventional generate-score-screenapproaches become impractical under such realistic design specifications,owing to their low search efficiency, unreliable generalizabilityof machine-learning predictions, and the prohibitive cost of quantumchemical calculations. Here, we present LUMOS, a data- and physics-drivenframework for inverse design of fluorescent molecules. LUMOS couplesthe generator and predictor within a shared latent representation,enabling direct specification-to-molecule design and efficient exploration.Moreover, LUMOS combines neural networks with a fast time-dependentdensity functional theory (TD-DFT) calculation workflow to build asuite of complementary predictors spanning different trade-offs inspeed, accuracy, and generalizability, enabling reliable propertyprediction across diverse scenarios. Finally, LUMOS employs a property-guideddiffusion model integrated with multiobjective evolutionary algorithms,enabling <em>de novo</em> design and molecular optimizationunder multiple objectives and constraints. Benchmarks across random,scaffold, and fluorophore splits show competitive or improved predictiveaccuracy together with enhanced physical consistency, while multiobjectiveoptimization yields substantially improved Pareto fronts over representativebaselines. Further validation using TD-DFT and molecular dynamics(MD) simulations demonstrates that LUMOS can generate valid fluorophoresthat meet various target specifications. Overall, these results establishLUMOS as a data-physics dual-driven framework for fluorophore inversedesign.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5190–5206"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formal Chemoenzymatic Skeletal Editing of Fusicoccane Core to Access 6-Aza-Fusicoccanes","authors":"Seiya Endo,&nbsp;Eigo Fukuda,&nbsp;Ken-ya Hori,&nbsp;Kei-ichi Murai,&nbsp;Atsushi Nakayama,&nbsp;Yoko Yasuno,&nbsp;Masayoshi Arai,&nbsp;Hajime Sato,&nbsp;Tomohisa Kuzuyama,&nbsp;Tetsuro Shinada","doi":"10.1021/jacsau.6c00833","DOIUrl":"https://doi.org/10.1021/jacsau.6c00833","url":null,"abstract":"<p>Fusicoccane (FC)-typediterpenoids constitute a family of cyclicditerpenoids featuring a 5/8/5-fused tricyclic carbon skeleton. Thesenatural products have attracted considerable attention owing to theirunique biological functions, including plant hormone-like propertiesand antiproliferative activities against cancer cells. Herein, wereport the stereoselective synthesis of 6-aza-FC-type analogs viaa chemoenzymatic skeletal editing approach using CotB2, a diterpenesynthase responsible for constructing the FC skeleton. Based on thebiosynthetic reaction mechanism, we designed an unnatural substratebearing an amide moiety at the C6–C7 position of geranylgeranylpyrophosphate. CotB2 promoted the cyclization of this substrate toafford an optically active 5/11-fused lactam in a stereoselectivemanner. Subsequent intramolecular cyclization of the resulting lactamthrough an epoxide intermediate furnished 6-aza-FC derivatives, inwhich the C6 carbon of FC skeleton is replaced with a nitrogen atom.Notably, one of the 6-aza-FC analogs exhibited selective cytotoxicitytoward cancer cells, while displaying reduced activity toward HUVECcells.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5207–5213"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Access to the Simplest N-Substituted Pyrroles from Furans Enabled by Tailored Photocatalysts","authors":"Hyeonbhin Byeon,&nbsp;Hojin Hong,&nbsp;Da Hye Lee,&nbsp;Yoonjee Park,&nbsp;Taeyang Ha,&nbsp;Ha Eun Kim,&nbsp;Yoonsu Park","doi":"10.1021/jacsau.6c01035","DOIUrl":"https://doi.org/10.1021/jacsau.6c01035","url":null,"abstract":"<p><em>N</em>-Methylpyrroles are important motifs in pharmaceuticalsand biologically relevant compounds, yet their synthesis commonlyrelies on direct <em>N</em>-methylation of N–H pyrroles,a process often limited by the instability of pyrrole and the useof toxic alkylating reagents under harsh conditions. Herein, we reporta photocatalytic strategy for the direct conversion of readily availablefurans to <em>N</em>-methylpyrroles. The reaction efficiencywas markedly improved compared to the first-generation catalytic protocolthrough the development of tailored photocatalysts. Combining skeletalediting with continuous-flow photochemistry, this method providesefficient access to <em>N</em>-methylpyrroles under mild conditionswhile avoiding preformed N–H pyrrole substrates and conventionalmethylating agents. The utility of the protocol was further demonstratedthrough the late-stage diversification of structurally complex molecules.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 8","pages":"4811–4818"},"PeriodicalIF":8.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148810152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating the Reactivity of Amine-Based Electrolytes for Stable Rechargeable Magnesium Batteries","authors":"Seonmo Yang,&nbsp;Jeongheon Seok,&nbsp;Junyoung Choi,&nbsp;Jinyoung Kim,&nbsp;Hyo Chul Ahn,&nbsp;Hayoung Ahn,&nbsp;Jihoon Oh,&nbsp;Minkwan Kim,&nbsp;Dongmin Park,&nbsp;Taemin Kang,&nbsp;Ben Dlugatch,&nbsp;Doron Aurbach,&nbsp;Yousung Jung,&nbsp;Jang Wook Choi","doi":"10.1021/jacsau.6c00724","DOIUrl":"https://doi.org/10.1021/jacsau.6c00724","url":null,"abstract":"<p>Despite their advantagescomplementary to lithium- and sodium-ionbatteries, rechargeable magnesium batteries (RMBs) still suffer frommultiple limitations that impede their commercialization. Amine-basedelectrolytes have recently emerged as promising options to overcomethe long-standing challenge of sluggish Mg²⁺ ion transportat the magnesium metal interface; however, their uncontrolled chemicaland electrochemical reactivity impairs cycling and calendar life.After screening a range of bidentate methoxyethylamine derivatives,we herein identify aminoacetaldehyde dimethyl acetal (ADMA)─functionalizedwith a methoxy substituent─as a single electrolyte solventthat achieves an optimal balance between interfacial ionic transportand (electro)chemical stability. These optimal properties are enabledby the concerted modulation of electron donicity and steric hindrancein ADMA. Consequently, the ADMA-based electrolyte delivers stablecycling for Mg||SS half-cells─even under operating protocolsincorporating intermittent rest periods─as well as for full-cellspaired with Mo₆S₈ and tellurium cathodes. Thisstudy demonstrates that longstanding interfacial issues at the Mgmetal anode in RMBs can be resolved through the sophisticated molecularengineering of scalable, bidentate methoxyethylamine electrolyte solvents.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 8","pages":"4655–4666"},"PeriodicalIF":8.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148810370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanism of the SepF N-Terminal Conformational Switch in Ring Assembly and Membrane Anchoring","authors":"Wenjing Liu,&nbsp;Chang Zhang,&nbsp;Mojie Duan,&nbsp;Meng Yao,&nbsp;Ziwei Chang,&nbsp;Jun Yang","doi":"10.1021/jacsau.6c00393","DOIUrl":"https://doi.org/10.1021/jacsau.6c00393","url":null,"abstract":"<p>Septum-forming protein (SepF) self-assembles into ring-shapedstructuresduring bacterial cell division, acting as a bridge that anchors theZ-ring to the cell membrane and thereby facilitates membrane remodelingand constriction. In this study, we elucidate how salt ions regulatethe ring assembly of SepF and its membrane anchoring using solid-stateNMR (ssNMR) spectroscopy in combination with biochemical methods.We show that the N-terminal fragment of SepF (residues 1–12)is highly dynamic and disordered under salt-free conditions, whichinhibits SepF ring assembly. In the presence of NaCl, this N-terminalfragment of SepF undergoes a conformational transition to a less flexibleand more ordered state, enabling ring assembly and enhancing its membraneanchoring. In contrast, a SepF mutant that assembles into noncurvedfibrils exhibits impaired membrane recruitment capability, highlightingthe crucial role of assembly curvature in membrane remodeling. Basedon these findings, we propose a mechanistic model in which the coordinationof ring assembly and membrane anchoring is critical for membrane remodeling,with NaCl-dependent modulation of the N-terminal fragment playinga central role. Our work provides atomic-level insights into how SepFresponds to environmental factors to regulate its conformation andassembly curvature, advancing our understanding of the functionalregulation of supramolecular machinery in bacterial cell division.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 8","pages":"4445–4457"},"PeriodicalIF":8.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148810416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereodynamic Helicenes for Chirality Sensing and Enantiomeric Assay through Diastereomeric Helical Enrichment","authors":"Debarghya Sarkar,&nbsp;Sabyasachi Bag,&nbsp;Kanyashree Jana,&nbsp;Meleppatt Sujith,&nbsp;Tadashi Mori,&nbsp;C. H. Suresh,&nbsp;Jarugu Narasimha Moorthy","doi":"10.1021/jacsau.6c00717","DOIUrl":"https://doi.org/10.1021/jacsau.6c00717","url":null,"abstract":"<p>Although several molecular systems that lead to helicallytwistedstructures upon binding with chiral analytes and produce strong Cottoneffects (CEs) in CD for chirality sensing and assay have been reported,helicene-based platforms as probes have not been much explored. Wedesigned and synthesized three stereodynamic regioisomeric oxahelicaldialdehydes (<strong>OD</strong>s)─<strong>OH-Prox</strong>, <strong>OH-Dist</strong>, and <strong>OH-Asym</strong>─along with an analogouscarbohelical dialdehyde (<strong>CH-Prox</strong>), and investigated themas probes for sensing chiral monoamines (<strong>MA</strong>s) and diamines(<strong>DA</strong>s). Reactions of all <strong>OD</strong>s with a cyclicchiral diamine, 1,2-cyclohexanediamine (<strong>DA1</strong>), producedmacrocyclic imine products with a 2:2 <strong>OD</strong>/<strong>DA1</strong> stoichiometry, which exhibited strong CEs in their CD spectra. Notably,the imine derived from <strong>OH-Prox</strong> displayed intense CEscharacteristic of helical structures, appearing in the 300–400nm region with a bisignate feature near the absorption edge. In contrast,the imines formed from <strong>OH-Dist</strong> and <strong>CH-Prox</strong> lacked this signature. Theoretical energy minimizations of the structuresof imine products suggest that the compact and rigid structure ofthe <strong>OH-Prox_DA1</strong> imine is responsible for the edge CEwith bisignation observed in its CD spectrum. Analogous but significantlyweaker CEs (5–7 fold lower), also indicative of helical structures,were observed for the imine products of <strong>OH-Prox</strong> withmonoamines <strong>MA1</strong> and <strong>MA2</strong>, reflecting reducedrigidity and partial enrichment of one helical form. For oppositestereoconfigurations of amine analytes, mirror-image CEs were consistentlyobserved for all dialdehyde probe systems. It is shown that the pronouncedCEs, arising from conformational locking with <strong>DA1</strong> andenantiomeric helical enrichment with <strong>MA</strong>s, enable thedetermination of absolute configuration as well as rapid assay ofenantiomeric excess of chiral amine analytes at very low concentrations(μM). The stereodynamic helical molecular platforms are thuscompellingly demonstrated as powerful systems for chirality sensingand assay─marking an advance in a field dominated heretoforeby helically twisted molecular frameworks.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 8","pages":"4626–4642"},"PeriodicalIF":8.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148810435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Enzyme Activity Via Noncovalent Association with DNA-Functionalized Nanoparticles","authors":"Seungheon Lee,&nbsp;Atri Bhattacharya,&nbsp;Regan Kuttler,&nbsp;Subrata Pandit,&nbsp;Busra Ozguney,&nbsp;Jackson Jacobi,&nbsp;Jeetain Mittal,&nbsp;Devleena Samanta","doi":"10.1021/jacsau.6c00921","DOIUrl":"https://doi.org/10.1021/jacsau.6c00921","url":null,"abstract":"<p>Enhancing enzyme performance without protein engineeringremainsa central challenge in biocatalysis. Here, we report the unusual discoverythat nanoparticles densely functionalized with DNA, commonly knownas spherical nucleic acids (SNAs), can bind enzymes without chemicalconjugation, affinity tags, or engineered recognition motifs and substantiallyincrease catalytic activity. Using cytochrome c as a model peroxidase,we show that noncovalent binding to SNAs increases the apparent turnovernumber by up to 15-fold. Mechanistic studies by varying DNA density,length, and nanoparticle core identity reveal that activity enhancementdoes not arise from free DNA or the nanoparticle core alone but fromthe three-dimensional, high-density presentation of DNA at the nanoparticlesurface. Consequently, similar effects are observed when gold coresare replaced with glucose oxidase or antibody cores. Moreover, activitymodulation also depends on DNA sequence, establishing sequence designas a programmable handle for tuning enzyme output. All-atom moleculardynamics simulations, binding studies, and circular dichroism furtherreveal that base-specific interactions reshape enzyme conformationalflexibility and increase active-site accessibility. This effect generalizesbeyond cytochrome c to catalase and carbonic anhydrase. Together,these findings establish SNAs as adaptable, sequence-programmableplatforms for enhancing and coordinating biocatalysis and expand theirfunctional scope into enzyme regulation.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 8","pages":"4410–4416"},"PeriodicalIF":8.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148810075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}