Nimisha Gautam,Sreejyothi P,Kaushik Soni,Subhajit Chakraborty,Subir Maji,Kalishankar Bhattacharyya,Swadhin K Mandal
{"title":"aNHC-Stabilized Low-Valent Phosphorus Compound: Exploring Dual Catalytic Activity via Nucleophilicity and P(I)/P(III) Redox Reactivity.","authors":"Nimisha Gautam,Sreejyothi P,Kaushik Soni,Subhajit Chakraborty,Subir Maji,Kalishankar Bhattacharyya,Swadhin K Mandal","doi":"10.1021/jacs.5c05832","DOIUrl":"https://doi.org/10.1021/jacs.5c05832","url":null,"abstract":"In this work, we present the synthesis and detailed characterization of a low-valent phosphorus compound, mesoionic N-heterocyclic phosphinidene (mNHP, 2), stabilized by an abnormal N-heterocyclic carbene (aNHC). Natural resonance theory analysis and the formation of a bis-borane adduct (confirmed by a single-crystal X-ray diffraction study) revealed that the phosphorus center in mNHP has access to two lone pairs of electrons, as expected for a P(I) species. Beyond its structural characterization, we also investigated both the nucleophilic and redox reactivity of mNHP. Its interactions with CO2 and CS2 demonstrated its nucleophilic capabilities, while its reaction with a C(Ar)-F bond highlighted its redox behavior through oxidative addition at the P(I) center, transforming it into a P(III) species. These dual reactivities were subsequently integrated into catalytic cycles, positioning mNHP as an effective low-valent, metal-free catalyst for the formylation of thiols using CO2 via nucleophilicity and hydrodefluorination of aryl fluoride compounds via the P(I)/P(III) redox cycle. Various spectroscopic investigations, including X-ray photoelectron spectroscopy (XPS), trapping of intermediates, and detailed DFT studies, helped us to understand the dual reactivity of this low-valent phosphorus compound.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"100 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311658","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}
Linh Duy Thai, Marco Neumaier, Christopher Barner-Kowollik
{"title":"Orthogonal Thiol Addition Chemistry Based on Ether Acrylates","authors":"Linh Duy Thai, Marco Neumaier, Christopher Barner-Kowollik","doi":"10.1021/jacs.5c08202","DOIUrl":"https://doi.org/10.1021/jacs.5c08202","url":null,"abstract":"The thiol-Michael and radical thiol–ene addition chemistries are extremely powerful tools for the construction of advanced soft matter materials. However, a critical challenge of these chemistries lies in their nonideal orthogonality in which both acrylates (Michael acceptors) and electron-rich olefins are active in a radical thiol–ene reaction. Herein, we show that by employing an ether acrylate (β-alkoxyacrylate), readily accessible via the efficient hydroxyl–yne click reaction, true orthogonality between activated double bonds can be achieved. Critically, we exploit the radical inactive property of the ether acrylate for the efficient synthesis of difficult-to-prepare sequence-defined main-chain macromolecular photoswitches and brush-like polymers. The results reported open a straightforward opportunity to synthetically access advanced materials with controllable properties.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"4 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312093","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}
Tanner C. Jankins, Barnabé Berger, Françoise A. Aouane, Sergio Barbeira-Arán, Christophe Didier, Bettina Hürlimann, Claudius Zimmer, Bill Morandi
{"title":"C–H Functionalization via Single Atom Metathesis of C–H and C–X Bonds","authors":"Tanner C. Jankins, Barnabé Berger, Françoise A. Aouane, Sergio Barbeira-Arán, Christophe Didier, Bettina Hürlimann, Claudius Zimmer, Bill Morandi","doi":"10.1021/jacs.5c04754","DOIUrl":"https://doi.org/10.1021/jacs.5c04754","url":null,"abstract":"Metathesis and reversible catalytic reactions are fundamentally intriguing and powerful tools in modern synthetic chemistry. While most reversible catalytic reactions are predicated on breaking and forming reactive functional groups, the ability to leverage the C–H bond as a functional group in metathesis reactions has proved to be exceptionally challenging. Here, we develop a C–H/C–X metathesis reaction through a radical swapping protocol where hydrogen and halogen are traded between molecules via reversible hydrogen atom transfer (HAT) and halogen atom transfer (XAT) that allows for mild C–H halogenation. The reversibility of this process allows for the selective dehalogenation of polyhalogenated products to form monohalogenated products. Leveraging the reversibility of this process, halogenated organic pollutants can also serve as halogen sources for C–H halogenation. In a broader context, this work establishes that incorporating reversible metathesis logic in C–H bond functionalization can provide complementary advantages in synthetic strategies.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"233 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312089","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":"C-Terminal Radical Oxidation Inhibits α-Synuclein Aggregation and Cytotoxicity via an Oxidative Oligomer-Disrupting Pathway","authors":"Xiaoli Wang, Tingting Liang, Anran Jin, Chenao Zhang, Jiaxin Zhou, Mingrui Li, Ziyi Sun, Gongyu Li","doi":"10.1021/jacs.5c06792","DOIUrl":"https://doi.org/10.1021/jacs.5c06792","url":null,"abstract":"α-Synuclein (α-Syn) aggregation is a hallmark of Parkinson’s disease and other neurodegenerative disorders. This study investigates the impact of controlled radical oxidation on α-Syn aggregation and associated cytotoxicity. Using a microscale low-temperature plasma device for submillisecond radical oxidation, combined with native ion mobility-mass spectrometry and liquid chromatography-tandem mass spectrometry, we demonstrate radical-directed preferential oxidation of the α-Syn C-terminal region. This targeted oxidation leads to the inhibition of protein aggregation and reduced cytotoxicity in SH-SY5Y cells. Mechanistic analysis reveals that ultrafast C-terminal radical oxidation impairs α-Syn oligomerization propensity, likely by preventing conformational transitions critical for forming stable amorphous deposits and well-ordered fibers. Notably, this inhibitory effect is specific to monomer oxidation prior to aggregation rather than oxidation of preformed fibers. Our findings unveil a novel oxidative oligomerization-disrupting pathway that modulates α-Syn fibrillization behavior, offering new insights into the complex interplay between oxidative stress and protein aggregation in neurodegenerative diseases. This study challenges conventional views of the detrimental role of oxidative stress in α-Syn pathology and suggests potential neuroprotective strategies based on targeted oxidative modifications.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"8 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312091","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":"Ultrafast Coherent Electron Transfer through Intermolecular Quantum Well States.","authors":"Xintong Li,Linjie Chen,Zehua Wang,Andi Li,Huimin Xu,Guangzhen Shen,Jianyi Liu,Xuefeng Cui,Shijing Tan,Jin Zhao,V Ara Apkarian,Bing Wang,Hrvoje Petek","doi":"10.1021/jacs.5c08068","DOIUrl":"https://doi.org/10.1021/jacs.5c08068","url":null,"abstract":"Molecular materials offer a boundless design palette for light absorption and charge transport in both natural photosynthesis and engineered photovoltaics. They function in combination as chromophores, donors, conductors, and acceptors, enabling the excitation and charge carrier transport through space and wire-like intramolecular pathways. Although quantum coherence is believed to enhance photoexcitation and photoinduced charge transfer, fluctuating and inhomogeneous environments accelerate decoherence. Here, we assemble a nanoporous medium consisting of a templated bipyridyl ethylene (BPE) molecule array on a Ag(111) surface that functions as an exceptional intermolecular nonnuclear quantum well conductor of coherent electron waves spanning over 20 Å length. Time-periodic driving of the Ag/BPE interface by femtosecond pulses promotes electrons into a ladder of Floquet quasi-energy donor states, where intermolecular quantum well states act as a resonant doorway for coherent electron transport into BPE/vacuum image potential acceptor states. The bifurcation of electron passage between the Floquet donor ladder and the charge transfer acceptor channel is recorded by projecting the active electrons into the photoemission continuum in an interferometric time- and angle-resolved multiphoton photoemission experiment. We find that exceptional decoupling of electrons from the metal substrate by the molecule-dressed vacuum preserves the coherence on the ∼150 fs time scale. This offers a new paradigm for quantum state design where a molecule-dressed vacuum mediates coherent electron transport in nanoporous molecular architectures.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"6 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311657","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}
Kaige Shi, John Janisch, Zhuanghe Ren, Zhen Meng, Deborah Israel, Duy Le, William E. Kaden, Talat S. Rahman, Xiaofeng Feng
{"title":"Ammonium Cation-Promoted CO2 Electroreduction on Au in Acidic Media","authors":"Kaige Shi, John Janisch, Zhuanghe Ren, Zhen Meng, Deborah Israel, Duy Le, William E. Kaden, Talat S. Rahman, Xiaofeng Feng","doi":"10.1021/jacs.5c08017","DOIUrl":"https://doi.org/10.1021/jacs.5c08017","url":null,"abstract":"The electrochemical reduction of CO<sub>2</sub> in acidic media has received considerable attention, as it can mitigate the carbonate formation issue. However, the available protons in acidic media can boost the hydrogen evolution reaction (HER), so alkali metal cations are generally employed to promote the CO<sub>2</sub> reduction reaction (CO<sub>2</sub>RR) while suppressing the HER. Here we report that NH<sub>4</sub><sup>+</sup> cations are more effective promoters of CO<sub>2</sub> electrolysis on Au in acidic media than Na<sup>+</sup> and K<sup>+</sup>, achieving a 3-fold improvement in the CO<sub>2</sub>RR activity. The promotional effect of NH<sub>4</sub><sup>+</sup> cations is mainly attributed to their enhanced electrostatic stabilization of the CO<sub>2</sub> adsorption, which is the rate-limiting step for the CO<sub>2</sub>RR on Au. An estimation of the local pH under relevant conditions indicates that NH<sub>4</sub><sup>+</sup> can mitigate the interfacial pH swing during the CO<sub>2</sub>RR compared to Na<sup>+</sup> and K<sup>+</sup>. Further studies on Au nanocatalysts of varying sizes indicate that the cation effect is independent of the catalytic sites. Our work advances the understanding of the cation effect on CO<sub>2</sub>RR using nonmetal cations and demonstrates a viable cation strategy to enhance CO<sub>2</sub> electrolysis.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"38 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312092","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}
Lang Li, Thorben Eggert, Karsten Reuter, Nicolas G. Hörmann
{"title":"Electron Spillover into Water Layers: A Quantum Leap in Understanding Capacitance Behavior","authors":"Lang Li, Thorben Eggert, Karsten Reuter, Nicolas G. Hörmann","doi":"10.1021/jacs.5c04728","DOIUrl":"https://doi.org/10.1021/jacs.5c04728","url":null,"abstract":"We investigate the electronic and molecular properties of the electrified Pt(111)–water interface using molecular dynamics simulations, leveraging electronic-structure-aware density-functional theory (DFT) and classical force field approaches. Electrification is induced by introducing excess electrons with homogeneously distributed, nonionic counter-charges, allowing for a targeted analysis of electronic and water density responses without interference from electrolyte ions. Our results reveal that, within the DFT framework, the Pt(111)–water interface deviates from the classical picture, where excess electronic charge remains localized at the metallic surface. Instead, approximately 30–40% of the electronic excess charge density penetrates into the interfacial water region─a behavior that is absent in vacuum conditions or when using classical force fields. This redistribution of charge provides a compelling explanation for long-standing discrepancies in the modeling of this interface, including the stabilization of partially charged interfacial species such as H<sup>+</sup> and most importantly the severe underestimation─by an order of magnitude─of the interfacial capacitance in force-field-based methods. Our findings highlight the crucial role of electronic charge spillover in defining interfacial behavior which provides critical insights about the approximations in classical descriptions and for the development of more accurate computational models of electrochemical systems.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"12 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312087","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":"Coordination Chemistry Meets Boron Helices: Cationic Double-Stranded Diborahelicates and Bora[7]helicenes with Multicolor Emission","authors":"Heechan Kim, Robert J. Gilliard, Jr.","doi":"10.1021/jacs.5c07436","DOIUrl":"https://doi.org/10.1021/jacs.5c07436","url":null,"abstract":"Helicates and helicenes represent two prominent classes of synthetic molecular helices, desirable for their potential in chiroptical applications. Incorporating boron into their backbone presents a promising strategy to enhance the optical properties; however, the development of boron-doped helical systems featuring tunable emission, high configurational stability, and strong chiroptical response has been limited by synthetic challenges. We report the chemistry of bora[7]helicene and its dimeric diborahelicate. While the dimeric form is thermodynamically favored in the haloborane precursor, saturation of the boron coordination sphere by exogenous carbene or carbone ligands induces monomerization, reverting the structure to the bora[7]helicene. By employing a variety of ligands, late-stage structural diversification was achieved, yielding the first examples of cationic boron helices, which show exceptional emission tunability across the entire visible spectrum, and chiroptical responses surpassing those of previously reported [7]helicenes. Theoretical studies indicate that the double-helix geometry and the intramolecular charge transfer play a significant role in achieving high dissymmetry factors.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"44 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312090","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}
Matthew J. Styles, Michelle E. Boursier, Cassandra M. Doody, Kayleigh E. Nyffeler, Helen E. Blackwell
{"title":"Insights into the Mechanisms of Small Molecule-Induced Agonism and Antagonism of a Quorum Sensing Receptor in Pseudomonas aeruginosa","authors":"Matthew J. Styles, Michelle E. Boursier, Cassandra M. Doody, Kayleigh E. Nyffeler, Helen E. Blackwell","doi":"10.1021/jacs.5c00523","DOIUrl":"https://doi.org/10.1021/jacs.5c00523","url":null,"abstract":"Common bacteria use chemical signals to assess their cell density in a process called quorum sensing (QS). The pathogen <i>Pseudomonas aeruginosa</i> utilizes QS to control many virulence factors and traits involved in infection. Two QS signals used by <i>P. aeruginosa</i> are <i>N</i>-acyl <span>l</span>-homoserine lactones, which are recognized by three LuxR-type receptors, LasR, QscR, and RhlR. Modulation of LuxR-type receptor activity with non-native small molecules has been the focus of extensive efforts to attenuate virulence in <i>P. aeruginosa</i>. However, further development of these compounds has been slowed by the limited understanding of their mechanisms of action, either as agonists or antagonists. Specifically, how binding of ligand effectively transduces information to the DNA binding domain of LuxR-type proteins to promote or inhibit DNA binding is largely unknown. Herein, we report a suite of biochemical and biophysical experiments to characterize the interactions between the QscR receptor and a collection of compounds that alters QscR activity in cell-based reporter assays. We use the results of these investigations to propose models for a “signal transduction” mechanism between the QscR ligand binding domain and DNA binding domain upon ligand-induced agonism and antagonism. These models are tied to receptor levels and thus could have different implications for ligand behavior at nonquorate and quorate populations. Our findings also suggest limitations of cell-based reporter assays as proxies for biophysical parameters of QscR transcriptional activity, and we outline other experiments that may avoid these limitations. The methods and models presented here should be broadly applicable to the LuxR-type receptor family.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"70 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312215","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}
Julia V. Burykina, Iana I. Surzhikova, Ruslan R. Shaydullin, Andrey D. Kobelev, Artem N. Fakhrutdinov, Kirill S. Kozlov, Valentine P. Ananikov
{"title":"Reconfiguration of Active Species under Light for Enhanced Photocatalysis","authors":"Julia V. Burykina, Iana I. Surzhikova, Ruslan R. Shaydullin, Andrey D. Kobelev, Artem N. Fakhrutdinov, Kirill S. Kozlov, Valentine P. Ananikov","doi":"10.1021/jacs.5c05052","DOIUrl":"https://doi.org/10.1021/jacs.5c05052","url":null,"abstract":"Photocatalysis has emerged as a cornerstone of synthetic chemistry, enabling mild and selective transformations by using sustainable light sources. A common assumption persists that most photocatalysts are taken for granted to function as monomorphic species throughout the catalytic cycle. Our findings challenge this premise and discover a new mechanistic picture, demonstrating that the evolution of the catalyst under light is not a degradation artifact but a productive and exploitable transformation pathway. Using phenothiazine (PHT) as a model, we demonstrate that light triggers <i>in situ</i> formation of a diverse “cocktail” of catalytically active dimer, trimer, oligomers and their oxides with unique photophysical and redox properties. These reconfigured species expand the usable light spectrum, including red light, and exhibit better catalytic performance in oxidative coupling and sulfide oxidation reactions. The reconfigured catalysts unlock multiwave activation, driving oxidative coupling and sulfide oxidation reactions with remarkable efficiency (up to 99% yield) across UV to red light (λ = 650 nm), far beyond the capabilities of the parent PHT. We introduce the ReAct-Light concept (Reconfigurable Active species under Light) to capture this dynamic, wavelength-adaptive behavior. The work provides an example of key mechanistic insight into dynamic catalyst evolution, opening the way for the design of next-generation adaptive catalysts with enhanced efficiency.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"24 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312222","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}