IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-08-26 DOI: 10.1021/jacsau.6c00596

Jun Ohnuki, Kei-ichi Okazaki

{"title":"Enhanced Sampling of Protein Conformations in AlphaFold3 with Repulsive Bias in the Diffusion Generative Model","authors":"Jun Ohnuki, Kei-ichi Okazaki","doi":"10.1021/jacsau.6c00596","DOIUrl":"https://doi.org/10.1021/jacsau.6c00596","url":null,"abstract":"Conformational changes in proteins are vital to theirfunctionyet remain challenging for state-of-the-art artificial intelligence,such as AlphaFold3 (AF3), to predict. It has been observed that AF3sometimes fails to capture ligand-induced conformational changes,even though it explicitly includes ligand molecules that induce suchchanges. To address this challenge, we develop an enhanced samplingscheme that leverages the diffusion-based generative model used inAF3 to predict protein structures. Interpreting the diffusion generativemodel as a stochastic sampling process analogous to molecular dynamics(MD) simulations, we introduce here a repulsive biasing potentialbetween predicted structures to explore wider conformational space.We demonstrate that the developed sampling scheme, AF3-ReD, successfullysamples multiple conformational states in the AF3 distribution, includingligand-bound conformations of motor, kinase, and transporter proteins,which are rarely captured by the default AF3 settings. Consistencywith experimentally determined structures not only at the global structurallevel but also in local ligand-binding poses confirms reliable conformationalsampling with AF3-ReD. Notably, AF3-ReD succeeded in sampling conformationalstates of transporters that were unresolved at the AF3 training cutoff.Compared to another strategy based on multiple sequence alignment(MSA), AF3-ReD predicted intermediate conformations that are relativelycloser to the stable states. Thus, AF3-ReD provides a promising approachto predicting dynamic conformational changes of proteins associatedwith ligand binding, which could be further extended to other diffusion-basedgenerative models, such as those for protein design, potentially expandingtheir accessible design space.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5010–5024"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067518","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}

引用次数: 0

Go-and-Stop Nanovehicles Enabled by Counterbalanced NIR Optical Engines 平衡近红外光学引擎实现的走走停停纳米车辆

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-08-19 DOI: 10.1021/jacsau.6c00299

Jing Wang, Jingjing Li, Ming Tang, Haomin Chen, Yaxin Sun, Wenqian Chen, Yong Zhang, Xiaohui Zhu

{"title":"Go-and-Stop Nanovehicles Enabled by Counterbalanced NIR Optical Engines","authors":"Jing Wang, Jingjing Li, Ming Tang, Haomin Chen, Yaxin Sun, Wenqian Chen, Yong Zhang, Xiaohui Zhu","doi":"10.1021/jacsau.6c00299","DOIUrl":"https://doi.org/10.1021/jacsau.6c00299","url":null,"abstract":"Nanomotors are promisingfor diverse applications due to theirability to convert energy into directional motion. However, precisecontrol of their motion is still difficult because creating requiredasymmetric nanostructures presents significant synthetic challenges.Inspired by automotive engine control, this study reports a generalstrategy for constructing optical nanomotors with programmable motion.For the first time, this approach implements a “Go and Stop”concept, leveraging dissimilar near-infrared (NIR) responsivitiesof upconversion nanoparticle (UCNP) to accelerate (“Go”)or brake (“Stop”) motion on demand. Specifically, thenanovehicle is designed via interface-guided anisotropic growth strategy,where half of a single upconversion nanoparticle (UCNP) is coatedwith a hydrophilic silica shell containing Au nanoseeds, while theother is covered by a hydrophobic periodic mesoporous organosilica(PMO) loaded with Roussin’s black salt (RBS). This dual hydrophilic/hydrophobicdesign is also applicable to other optical materials, thus demonstratinggreat flexibility. When excited at 980 nm, blue light emitted by theUCNP activates the RBS to release nitric oxide (NO), propelling thenanomotor forward. Conversely, light at 808 nm induces gold-mediatedthermophoresis, which reduces and eventually stops NO-driven motion.Such “pull–push” effect enables the nanomotorto start, accelerate, decelerate, and stop simply by switching theexcitation light. As a proof of concept, the nanovehicle is furtherused to noninvasively regulate cellular endocytosis and has demonstratedgreat potentials for programmable tumor treatment.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"4910–4921"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067548","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}

引用次数: 0

Lysine-Targeting Covalent Inhibition of Glutaminase Using Cyanopyrimidines 以赖氨酸为靶点的谷氨酰胺酶的氰嘧啶共价抑制

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-09-03 DOI: 10.1021/jacsau.6c00924

Xiwen Xiao, Hibiki Okuno, Saki Inoue, Naoki Zenmyo, Yuya Matsumoto, Emi Mishiro-Sato, Keiko Kano, Kazuaki Yoshimune, Shohei Uchinomiya, Akio Ojida

引用次数: 0

SNAr-Functionalization of Diaryliodonium Salts: Access to Densely Substituted Arenes 二芳基碘鎓盐的snar功能化：获得密取代芳烃

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-09-10 DOI: 10.1021/jacsau.6c01053

Leonard Kersting, Judith Braunreuther, Erika Linde, Berit Olofsson

引用次数: 0

On-Cycle Enforcement in Water: Trimetallic Assemblies Preventing Pd Black Formation While Accelerating Selective Suzuki–Miyaura Coupling without Olefin Interference 在水中循环执行：三金属组件防止Pd黑的形成，同时加速没有烯烃干扰的选择性Suzuki-Miyaura耦合

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-07-31 DOI: 10.1021/jacsau.6c00796

Sudripet Sharma, Uyen Duong, Maarten Nachtegaal, Adam H. Clark, Ramesh Hiralal Choudhary, Jacek B. Jasinski, Wilfried Braje, Sachin Handa

{"title":"On-Cycle Enforcement in Water: Trimetallic Assemblies Preventing Pd Black Formation While Accelerating Selective Suzuki–Miyaura Coupling without Olefin Interference","authors":"Sudripet Sharma, Uyen Duong, Maarten Nachtegaal, Adam H. Clark, Ramesh Hiralal Choudhary, Jacek B. Jasinski, Wilfried Braje, Sachin Handa","doi":"10.1021/jacsau.6c00796","DOIUrl":"https://doi.org/10.1021/jacsau.6c00796","url":null,"abstract":"Palladium-catalyzed cross-couplings are frequently limitedby off-cycledeactivation pathways, particularly phosphine deligation followedby aggregation of Pd(0) to catalytically inactive palladium black.We report an “on-cycle enforcement” strategy that employsa cooperative, nonalloyed trimetallic assembly─Pd(0), Cu(I),and Mn(III)─confined within PS-750-M/HPMC micelles in water.In this architecture, Pd mediates the canonical oxidative additionand reductive elimination steps, Cu(I) accelerates transmetalationvia a Cu-nucleophile intermediate, and Mn(II/III) serves as a redoxbuffer that likely continuously reoxidizes off-cycle Pd(0) to micelle-solublePd(II), followed by its religation and reduction, thereby preventingPd black formation. Spectroscopic analysis─transmission electronmicroscopy, scanning transmission electron microscopy–high-angleannular dark-field imaging, energy-dispersive X-ray spectroscopy,X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy─revealsthat the three metals remain spatially separated in the assembly yetelectronically complementary within a phosphorus-rich matrix, enablingpersistent catalytic activity. The resulting platform supports rapid,selective C–C couplings at 45 °C with broad substratecompatibility, including heteroarenes and terminal olefin─containingpartners, without olefin interference. The catalyst displays exceptionallongevity, minimal metal leaching (<1 ppm), and robust scalability,with multicycle reactions and gram-scale processes proceeding efficientlyeven after extended catalyst storage. These findings establish redox-buffered,compartmentalized trimetallic assemblies as a general solution toenforcing on-cycle Pd catalysis in water.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5145–5153"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067571","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}

引用次数: 0

Evidence for Site-Specific Tunneling in H Atom Uptake at the Surface of Polyoxovanadate-Alkoxides 多氧钒酸盐-烷氧化合物表面H原子吸收的位点特异性隧穿证据

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-08-19 DOI: 10.1021/jacsau.6c00947

M. Rebecca A. Walls, Shannon E. Cooney, Ellen M. Matson

{"title":"Evidence for Site-Specific Tunneling in H Atom Uptake at the Surface of Polyoxovanadate-Alkoxides","authors":"M. Rebecca A. Walls, Shannon E. Cooney, Ellen M. Matson","doi":"10.1021/jacsau.6c00947","DOIUrl":"https://doi.org/10.1021/jacsau.6c00947","url":null,"abstract":"Lindqvist-type polyoxovanadate-alkoxidesare used asatomicallyprecise, soluble analogs of metal oxides to interrogate site-dependent(e.g., μ2-oxido vs terminal oxido) tunneling in proton-coupledelectron transfer (PCET). Variable-temperature kinetic isotope effect(VT-KIE) analysis reveals that H atom uptake at the μ2-oxido site of [TBA]2[V6O8(OCH3)11] proceeds via quantum mechanical tunnelingin acetonitrile, evidenced by a temperature-independent KIE, a smallisotopic effect on activation energy, and positive Arrhenius prefactorratio. This behavior is in contrast to PCET at the terminal vanadylsite of [TBA][V6O7(OCH3)12], which follows a semiclassical, concerted proton–electrontransfer mechanism. Tunneling effects are solvent dependent; switchingto dimethylformamide, a more basic solvent, results in a reductionin H-bonding interactions with the acceptor, lowering the observedrate of H atom uptake at the bridging site. This work highlights therole of site-specific basicity on tunneling in metal oxides, wherecompetitive H-bonding with solvent disrupts tunneling.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5287–5294"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149071074","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}

引用次数: 0

DNA Nanotechnology in the Undergraduate Laboratory: Isothermal Assembly and Quantification of DNA Nanostructures 本科实验室中的DNA纳米技术：DNA纳米结构的等温组装和定量

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-09-04 DOI: 10.1021/jacsau.6c01181

Hannah Talbot, Sarah Youssef, Arun Richard Chandrasekaran

引用次数: 0

Optoglycomics: Synthesis and Function of Photochromic Glycoconjugates 光糖组学：光致变色糖缀合物的合成和功能

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-08-28 DOI: 10.1021/jacsau.6c01067

Guillaume Despras, Thisbe K. Lindhorst

引用次数: 0

Designing Heterolytic and Homolytic Bond Scission in Diarylmethane Mechanophores 二芳基甲烷机械载体异裂解和均裂解键断裂的设计

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-08-17 DOI: 10.1021/jacsau.6c00989

Gaia Egizzo, Eduardo García-Padilla, Federico Frateloreto, Florent Monie, Dnyaneshwar Ajinath Mache, Feliu Maseras, José Augusto Berrocal

{"title":"Designing Heterolytic and Homolytic Bond Scission in Diarylmethane Mechanophores","authors":"Gaia Egizzo, Eduardo García-Padilla, Federico Frateloreto, Florent Monie, Dnyaneshwar Ajinath Mache, Feliu Maseras, José Augusto Berrocal","doi":"10.1021/jacsau.6c00989","DOIUrl":"https://doi.org/10.1021/jacsau.6c00989","url":null,"abstract":"Mechanical forcecan often unlock chemical reactivity inaccessibleunder conventional conditions. However, understanding how molecularstructure and environment govern mechanochemical reaction pathwaysin the solid state remains a significant challenge. In particular,establishing design principles to access heterolytic bond scissionin nonpolar materials remains elusive. Here, we investigate a familyof diarylmethane-based mechanophores embedded in polymer networksto elucidate how bond identity, substituent electronics, leaving-groupstabilization, and matrix interactions collectively determine mechanochemicalreactivity. By systematically varying the nature of the scissile bond(C–O vs C–C), the electronic properties of the diarylmethanecore, and the presence or absence of hydrogen-bonding functionalitiesin the surrounding polymer matrix, we establish structure–reactivityrelationships that govern the formation of radical and ionic speciesunder tensile load. Mechanophores containing C–O bonds displayenvironment-dependent behavior, with homolytic cleavage dominatingin non-hydrogen-bonding matrices and heterolytic scission accessibleonly when both strongly donating substituents and hydrogen-bond donorsare present. In contrast, mechanophores incorporating polarized C–Cbonds with strongly stabilizing leaving groups undergo heterolyticcleavage to yield diarylcarbenium ions, even in matrices lacking hydrogen-bondingfunctionality. These results establish design principles linking molecularstructure and polymer environment to mechanochemical reactivity anddemonstrate that ionic pathways can be accessed and stabilized inthe solid state. More broadly, this work provides guidelines for designingmechanoresponsive materials with distinct reaction pathways and mechanochromicresponses.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5307–5316"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067543","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}

引用次数: 0

Electron-Donor–Acceptor Enabled Electrophilic C(sp2)-C(sp3) Cross-Coupling 电子供体-受体使能的亲电性C(sp2)-C（sp3）交叉耦合

IF 8.5

JACS Au Pub Date : 2026-09-28 Epub Date: 2026-08-14 DOI: 10.1021/jacsau.6c01012

Zheng Wang, Xiaodong Qiu, Burkhard König

引用次数: 0

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