Accounts of Chemical Research最新文献

{"title":"","authors":"Wei Ou,  and , Pei-Qiang Huang*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 14","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Aldehyde Sensing Probes for In Vivo Imaging.","authors":"Yingying Ning, Eman A Akam-Baxter, Peter Caravan","doi":"10.1021/acs.accounts.5c00200","DOIUrl":"10.1021/acs.accounts.5c00200","url":null,"abstract":"<p><p>ConspectusCarbonyl-ligation reactions are considered to be largely bioorthogonal due to the rarity of ketones and aldehydes in normal mammalian biology, especially in the extracellular space. However, during development, in wound healing, or in response to many disease conditions, certain extracellular matrix (ECM) proteins can be post-translationally modified by lysyl oxidases to contain aldehyde-bearing side chains. In many diseases, accelerated ECM production is a part of a process called fibrosis (scarring of tissue), and about half of the deaths in the industrialized world arise from disease with a fibrotic component. During fibrogenesis (active fibrosis), lysyl oxidases are upregulated, catalyzing the oxidation of lysine residues on ECM proteins to form lysine aldehyde (allysine, Lys<sup>Ald</sup>). Lys<sup>Ald</sup> undergoes condensation reactions with other Lys<sup>Ald</sup> or Lys residues of adjacent collagens to cross-link proteins. Despite the centrality of fibrogenesis in development and in so many diseases, there is a general lack of tools to noninvasively detect and quantify fibrogenesis in humans or in animal models. Our group used rational design to develop molecular probes for Lys<sup>Ald</sup> to enable the detection, staging, and treatment monitoring of fibrogenesis. In this Account, we summarize our design strategies and validation methods of Lys<sup>Ald</sup> targeting probes for applications in a wide range of diseases with a fibroproliferative component.The Lys<sup>Ald</sup> concentrations exhibit distinct organ- and tissue-specific variations in the progression of fibrogenesis. To increase the sensitivity of Lys<sup>Ald</sup> probes, we systematically optimized the probe structures to modulate the kinetics of aldehyde condensation reactions and the reverse hydrolysis reaction, molecular hydrophilicity, pharmacokinetics, and elimination. Incorporating electron-withdrawing groups, acidic moieties, and dual-binding ligands significantly enhanced the condensation rates. Combining these strategies with signal amplification by designing \"off-on\" probes, we extended the probe applicability from organs of high Lys<sup>Ald</sup> levels (lung) to low-concentration systems (liver, tumor, and cardiac tissues). Reducing the hydrolysis rate of the probe-Lys<sup>Ald</sup> adduct extended the imaging window and permitted the specific detection of Lys<sup>Ald</sup> in the kidneys. Importantly, our design strategies demonstrate multimodal compatibility, validated through magnetic resonance imaging, positron emission tomography, and fluorescence imaging platforms. The multiscale detection capability in different imaging modalities (cellular to in vivo) provides critical spatial-temporal insights into fibroproliferative disease dynamics in different species and tissues, including onset, progression, and therapeutic response. While this Account focuses on the design of molecular probes for Lys<sup>Ald</sup>, the strategies employed her","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"2203-2215"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525230","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":"Microenvironment Engineering of Mesoporous Metals for Ammonia Electrosynthesis from Nitrate: Advances, Mechanisms, and Prospects.","authors":"Lizhi Sun, Ben Liu","doi":"10.1021/acs.accounts.5c00327","DOIUrl":"10.1021/acs.accounts.5c00327","url":null,"abstract":"<p><p>ConspectusElectrocatalytic nitrate reduction to ammonia (NO₃^--to-NH₃) offers a promising pathway to convert NO₃^- wastewater to high-value-added NH₃ under ambient conditions with renewable electricity. The design of robust electrocatalysts that facilitate the completion of complex hydrodeoxygenation steps is a major challenge for efficient NH₃ electrosynthesis from NO₃^-. Mesoporous metals, as a fantastic class of mesoscopic functional materials, not only retain the ability to control electrocatalytic nitrate reduction reactions (eNO₃RR) at the atomic/molecular level but also induce new physicochemical properties with the nanoconfined mesoporous microenvironment. In this Account, we outline our recent progress in engineering the surface microenvironment of mesoporous metals to enhance the electrocatalytic NO₃^--to-NH₃ performance.We start by introducing nanoconfinement effects to validate the mechanism of mesoporous metals on key intermediates in eNO₃RR. Unlike conventional nonporous counterparts, nanoscale pores and channels of mesoporous metals present strong nanoconfinement of nitrogen-containing intermediates and active hydrogen (*H) radicals, which promotes the deeper electroreduction of NO₃^- by multistep hydrodeoxygenation routes and results in remarkable NH₃ selectivity. To resolve the key challenge of longer mesopores that severely limit mass transfer efficiency, hierarchical mesoporous metals, including hollow mesoporous nanotubes and mesoporous nanocavities, are designed that effectively realize the synergistic promotion of NH₃ yield rate and selectivity. Next, an enzyme-like tandem electrocatalyst with separated metal active sites is developed to alleviate the kinetic barrier of eNO₃RR, which thus achieves NH₃ electrosynthesis at ultralow overpotentials. Through coupling with anode oxygen reactions with mesoporous metals as a bifunctional electrocatalyst, eNO₃RR is further promoted and delivers better performance for NH₃ electrosynthesis in a more sustainable manner. Finally, we present the limitations and challenges in designing functional mesoporous metal electrocatalysts and propose prospects for further development of eNO₃RR technologies. We hope that this Account will open an alternative in designing efficient mesoporous metals with optimized surface microenvironments for selective electrocatalysis and beyond.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"2306-2316"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558348","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":"","authors":"Can Guo,&nbsp;Pan Xue,&nbsp;Fengxue Duan,&nbsp;Yifa Chen* and Ya-Qian Lan*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 14","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Morgan Murphy,&nbsp;Amal Mohamed,&nbsp;John V. Badding and Elizabeth Elacqua*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 14","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Underscoring Covalent-Organic Frameworks As Nanoengines for Zinc Anode Protection Coating.","authors":"Can Guo, Pan Xue, Fengxue Duan, Yifa Chen, Ya-Qian Lan","doi":"10.1021/acs.accounts.5c00226","DOIUrl":"10.1021/acs.accounts.5c00226","url":null,"abstract":"<p><p>ConspectusRechargeable aqueous zinc-ion batteries (AZIBs) have emerged as promising energy storage systems owing to their high energy density, environmental benignity, and low cost. Nevertheless, the rough surface of the Zn metal anode can easily induce uncontrolled dendrite growth and parasitic reactions, which will limit the large-scale commercial applications of AZIBs. Owing to the diverse active sites and porous channels of covalent-organic frameworks (COFs), the exploration of COFs in this field affords a novel perspective in tackling the bottlenecks encountered through the anode of AZIBs. Based on reported works, this review summarizes the functions of COFs as nanoengines to manipulate the Zn²⁺ flux, hydrogen evolution, dendrite growth, and the electric field at electrode/electrolyte interface when applied as functional coatings. It also concludes the construction strategies of functional COFs coating and delves into strategies for protecting the Zn anode, with an emphasis on modulating Zn deposition dynamics and minimizing side reactions at the electrode/electrolyte interface. It further provides an evaluation of the current challenges and future expectations of AZIB, aiming to enhance their viability for grid-scale energy storage solutions.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"2229-2242"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504060","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":"The Role of Anions in Guanidinium-Catalyzed Chiral Cation Ion Pair Catalysis.","authors":"Wentao Wu, Chu Liu, Choon-Hong Tan, Xinyi Ye","doi":"10.1021/acs.accounts.5c00283","DOIUrl":"10.1021/acs.accounts.5c00283","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusCatalysts drive asymmetric transformations by orchestrating a network of covalent and noncovalent interactions that precisely regulate the reactivity and stereoselectivity. Ion pair catalysis, developed based on the inherent strength and long-range nature of ionic interactions, has demonstrated high catalytic efficiency and broad applicability. While chiral cationic catalysts have long been central to this field, the critical roles of their counteranions have historically been overlooked. Over the past 15 years, we have developed a class of &lt;i&gt;N&lt;/i&gt;-sp&lt;sup&gt;2&lt;/sup&gt;-hybridized guanidinium chiral cation ion pair catalysts, which have been widely applied in enantioselective reactions. In this Account, we present new insights into these catalysts, revealing how the roles of anions, acting as substrates, reagents, and cocatalysts, can be strategically leveraged to achieve remarkable enantioselectivity across a wide range of organic transformations.When acting as substrates, anions, such as sulfinates, thiocarboxylates, and azides, are rendered reactive through intimate ion pairing with the chiral guanidinium moiety. This strategy facilitates desymmetrization processes, exemplified by the conversion of sulfinates to enantioenriched sulfinate esters and the remote desymmetrization of &lt;i&gt;cis&lt;/i&gt;-dibromocyclohexanone via sequential S&lt;sub&gt;N&lt;/sub&gt;2 and acyl transfer steps. Mechanistically, halogenophilic S&lt;sub&gt;N&lt;/sub&gt;2X pathways (e.g., thiocarboxylate substitutions at sterically hindered tertiary carbons) bypass traditional steric limitations, while dynamic kinetic resolution of racemic bromides via azide substitution highlights the interplay between ion exchange and interfacial dynamics.Anions generated &lt;i&gt;in situ&lt;/i&gt; from stoichiometric reagents give rise to highly reactive intermediates such as enolates, sulfenates, and hypervalent silicates, which form ion pairs with chiral cations, enabling enantioselective transformations. For instance, enolates displace tertiary bromides via an S&lt;sub&gt;N&lt;/sub&gt;2X mechanism (frontside attack), circumventing steric hindrance. Sulfur alkylation of sulfenamides yields chiral sulfilimines, while fluoride-activated acylsilanes undergo Brook-like rearrangements through penta-coordinate silicates. Silicon hydrides activated by fluoride form hydridosilicates, enabling enantioselective conjugate reductions of chromones and coumarins. The versatility of ion pairing is further illustrated by α-cyano carbanions in Pd-catalyzed decarboxylative allylic alkylations and is extended to a cooperative catalytic system, where DMAP-generated nucleophiles enable enantioselective phospha-Michael additions via dynamic cation-exchange activation.The utilization of inorganic anions as cocatalysts further expands the scope of chiral cation ion pair catalysis. Peroxytungstate anions synergize with chiral cations to enable the epoxidation of allylic amines, while peroxomolybdate facilitates the &lt;i&gt;N&lt;/i&gt;-oxidation of tertiary amines wi","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"2269-2281"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525231","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":"","authors":"Isaiah W. Gilley,&nbsp;Taylor E. Wiggins,&nbsp;Edward H. Sargent* and Mercouri G. Kanatzidis*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 14","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Mannich-Type Multicomponent Reactions: Discovery, Mechanism, and Application.","authors":"Xianjing Zhou, Zhencheng Lai, Jiaming Li, Chengcheng Fan, Sunliang Cui","doi":"10.1021/acs.accounts.5c00338","DOIUrl":"10.1021/acs.accounts.5c00338","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusThe development of efficient multicomponent reactions (MCRs) represents a vital frontier for the rapid construction of structurally sophisticated molecules from simple precursors in an atom- and step-economic manner. In particular, the Mannich reaction is a prototypical three-component reaction that rapidly assembles a resonance-stabilized carbon nucleophile, an aldehyde (or ketone), and an amine to afford alkylamines and serves as a particularly valuable tool for diversity-oriented synthesis in drug discovery and development. Typically, the nucleophilic components of the Mannich reaction rely on Brønsted-acidic carbonyl C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;3&lt;/sup&gt;)-H and electron-rich aromatic C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;)-H. However, the development of Mannich reactions involving unactivated C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;3&lt;/sup&gt;)-H remains a formidable challenge, which would be largely attributed to their difficult deprotonation and therefore non-nucleophilic properties.In this Account, we detail the journey from a serendipitous discovery to mechanistic elucidation, wherein an unprecedented double Mannich alkylamination occurred in both C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;)-H and unactivated benzylic C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;3&lt;/sup&gt;)-H bonds to eventually enable alkylaminative cyclization. Mechanistic studies revealed a distinctive pathway in which a multiple Mannich and &lt;i&gt;retro&lt;/i&gt;-Mannich process and the dehydrogenation of benzylic C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;3&lt;/sup&gt;)-H bonds were key steps to constitute the alkylamination. Enlightened by the mechanistic investigations, our group successfully developed a series of Mannich-type MCRs in which benzofurans/indoles, formaldehyde, and alkylamine hydrochlorides assemble efficiently to furnish piperidine-fused benzofurans/indoles, demonstrating broad compatibility with medicinally relevant functionalities. Inspired by the dual C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;)-H/C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;3&lt;/sup&gt;)-H alkylaminative cyclization paradigm, we developed a unique Mannich-type MCR of indoles wherein the MCR process occurred in both N-H and the adjacent 2-position C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;)-H bonds to access indole-fused seven-membered heterocycles.More importantly, these MCRs serve as a powerful synthetic toolbox in the scaffold evolution of natural products as well as in drug discovery and development. Notably, the modification of natural products (NPs) presents significant challenges due to their inherent structural complexity, and thus efficient synthetic methods could enable more accessible modification of NPs, thereby unlocking their full therapeutic potential. We employed our established MCRs to successfully achieve an innovative scaffold evolution of natural product tanshinones, in which the highly lipophilic tanshinones could be easily transformed to &lt;i&gt;N&lt;/i&gt;-heterocyclic scaffolds with improved functionality, drug-likeness, and biological specificity. As a result, we have pioneered the chemical evolution of Tan I for the discovery of a new class of potent NLRP3 inflammasome i","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"2317-2331"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537366","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":"","authors":"Yi-Qi Zhang*,&nbsp;Jonas Björk* and Johannes V. Barth,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 14","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}