ACS Combinatorial Science最新文献

{"title":"Phototriggered Hydrogen Persulfide Donors via Hydrosulfide Radical Formation Enhancing the Reactive Sulfur Metabolome in Cells","authors":"Biswajit Roy,&nbsp;Meg Shieh,&nbsp;Tsuyoshi Takata,&nbsp;Minkyung Jung,&nbsp;Eshani Das,&nbsp;Shi Xu,&nbsp;Takaaki Akaike and Ming Xian*,&nbsp;","doi":"10.1021/jacs.4c1154010.1021/jacs.4c11540","DOIUrl":"https://doi.org/10.1021/jacs.4c11540https://doi.org/10.1021/jacs.4c11540","url":null,"abstract":"<p >Hydrogen persulfide (H₂S₂) is an important sulfur-containing signaling molecule that plays a crucial role in the homeostasis of various organ systems, such as the renal, cardiovascular, liver, and gastrointestinal systems. However, research on H₂S₂ in biological settings is still challenging due to its instability and high reactivity. Compounds that can controllably release H₂S₂ (also known as donors) are thus crucial research tools. Currently, available H₂S₂ donors are still very limited, with most of them relying on modified disulfide templates. These templates possess an unavoidable limitation of being susceptible to cellular disulfide exchange which can compromise their efficacy. In this work, we explored nondisulfide-based and nonoxidation-dependent templates for the design of H₂S₂ donors. We found that tertiary naphthacyl thiols could undergo phototriggered C–S homolytic cleavage to form H₂S₂ via hydrosulfide (HS) radicals. In addition, the release of H₂S₂ was associated with the formation of a product with strong blue fluorescence, which allowed for real-time monitoring of the release process. This reaction was demonstrated to proceed effectively in both buffers and cells, with the ability to enhance intracellular production of persulfides, including GSSH, CysSSH, H₂S₂, H₂S₃, etc. It provides a unique photocontrolled H₂S₂ donor system with distinct advantages compared to known H₂S₂ donors due to its good stability and spatiotemporal control ability.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30502–30509 30502–30509"},"PeriodicalIF":14.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Plasticity as a Driver of the Maturation of Pro-Interleukin-18","authors":"Jeffrey P. Bonin*,&nbsp;James M. Aramini and Lewis E. Kay*,&nbsp;","doi":"10.1021/jacs.4c0980510.1021/jacs.4c09805","DOIUrl":"https://doi.org/10.1021/jacs.4c09805https://doi.org/10.1021/jacs.4c09805","url":null,"abstract":"<p >Dynamics are often critical for biomolecular function. Herein we explore the role of motion in driving the maturation process of pro-IL-18, a potent pro-inflammatory cytokine that is cleaved by caspases-1 and -4 to generate the mature form of the protein. An NMR dynamics study of pro-IL-18, probing time scales over 12 orders of magnitude and focusing on ¹H, ¹³C, and ¹⁵N spin probes along the protein backbone and amino-acid side chains, reveals a plastic structure, with millisecond time scale dynamics occurring in a pair of β-strands, β1 and β*, that show large structural variations in a comparison of caspase-free and bound pro-IL-18 states. Fits of the relaxation data to a three-site model of exchange showed that the ground state secondary structure is maintained in the excited conformers, with the side chain of I48 that undergoes a buried-to-exposed conformational change in the caspase-free to -bound transition of pro-IL-18, sampling a more extensive range of torsion angles in one of the excited states characterized, suggesting partial unpacking in this region. Hydrogen exchange measurements establish the occurrence of an additional process, whereby strands β1 and β* locally unfold. Our data are consistent with a hierarchy of dynamic events that likely prime pro-IL-18 for facile caspase binding.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30281–30293 30281–30293"},"PeriodicalIF":14.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Covalent Bonds versus van der Waals Forces: A Picture in Thermal Conduction of Organic Materials","authors":"Ryosuke Takehara,&nbsp;Tomoya Fukui,&nbsp;Taketo Tano,&nbsp;Meguya Ryu,&nbsp;Suguru Kitani,&nbsp;Hitoshi Kawaji,&nbsp;Junko Morikawa* and Takanori Fukushima*,&nbsp;","doi":"10.1021/jacs.4c1184910.1021/jacs.4c11849","DOIUrl":"https://doi.org/10.1021/jacs.4c11849https://doi.org/10.1021/jacs.4c11849","url":null,"abstract":"<p >We present a direct comparison of the heat transport properties between the state in which the constituent molecules are assembled by intermolecular forces and the one in which they are covalently bonded, in a molecular system with identical constituent elements and masses, as well as a nearly identical structure and density. This comparison leading to an essential understanding of thermal conduction in organic materials is made possible by the unique compound found by Wudl et al., which exhibits a single-crystal-to-single-crystal topochemical polymerization with a yield of &gt;99%, in combination with microtemperature wave analysis (<i>μ</i>TWA), which allows accurate measurements of the thermal diffusivity of small single crystals. At room temperature, the thermal conductivity of monomer and polymer single crystals is not significantly different. For both crystals, the thermal conductivity increases monotonically with decreasing temperature. However, below the Debye temperature, the thermal conductivity of the polymer single crystal increases exponentially, giving much larger values than those of the monomer single crystal. Based on physical quantities related to the behavior of phonons, derived from the specific heat analysis, we discuss the differences in heat transport properties in the two states and provide guidelines for achieving high thermal conductivity in organic materials.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30548–30552 30548–30552"},"PeriodicalIF":14.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacs.4c11849","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Entropy Magnet Enabling Distinctive Thermal Expansions in Intermetallic Compounds","authors":"Jinghan Li,&nbsp;Kun Lin*,&nbsp;Hankun Xu,&nbsp;Wanda Yang,&nbsp;Qian Zhang,&nbsp;Chengyi Yu,&nbsp;Qinghua Zhang,&nbsp;Jing Chen,&nbsp;Chin-Wei Wang,&nbsp;Kenichi Kato,&nbsp;Shogo Kawaguchi,&nbsp;Li You,&nbsp;Yili Cao,&nbsp;Qiang Li,&nbsp;Xin Chen,&nbsp;Jun Miao,&nbsp;Jinxia Deng and Xianran Xing,&nbsp;","doi":"10.1021/jacs.4c1068110.1021/jacs.4c10681","DOIUrl":"https://doi.org/10.1021/jacs.4c10681https://doi.org/10.1021/jacs.4c10681","url":null,"abstract":"<p >The high-entropy strategy has gained increasing popularity in the design of functional materials due to its four core effects. In this study, we introduce the concept of a “high-entropy magnet (HEM)”, which integrates diverse magnetic compounds within a single phase and is anticipated to demonstrate unique magnetism-related properties beyond that of its individual components. This concept is exemplified in AB₂-type layered Kagome intermetallic compounds (Ti,Zr,Hf,Nb,Fe)Fe₂. It is revealed that the competition among individual magnetic states and the presence of magnetic Fe in originally nonmagnetic high-entropy sites lead to intricate magnetic transitions with temperature. Consequently, unusual transformations in thermal expansion property (from positive to zero, negative, and back to near zero) are observed. Specifically, a near-zero thermal expansion is achieved over a wide temperature range (10–360 K, α_v = −0.62 × 10^–6 K^–1) in the A-site equal-atomic ratio (Ti_1/5Zr_1/5Hf_1/5Nb_1/5Fe_1/5)Fe₂ compound, which is associated with successive deflection of average Fe moments. The HEM strategy holds promise for discovering new functionalities in solid materials.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30380–30387 30380–30387"},"PeriodicalIF":14.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composite Recycling with Biocatalytic Thermoset Reforming","authors":"Clarissa Olivar,&nbsp;Zehan Yu,&nbsp;Ben Miller,&nbsp;Maria Tangalos,&nbsp;Cory B. Jenkinson,&nbsp;Steven R. Nutt,&nbsp;Berl R. Oakley,&nbsp;Clay C. C. Wang* and Travis J. Williams*,&nbsp;","doi":"10.1021/jacs.4c1083810.1021/jacs.4c10838","DOIUrl":"https://doi.org/10.1021/jacs.4c10838https://doi.org/10.1021/jacs.4c10838","url":null,"abstract":"<p >Carbon fiber reinforced polymers (CFRPs, or composites) are increasingly replacing traditional manufacturing materials used in the automobile, aerospace, and energy sectors. With this shift, it is vital to develop end-of-life processes for CFRPs that retain the value of both the carbon fibers and the polymer matrix. Here we demonstrate a strategy to upcycle pre- and postconsumer polystyrene-containing CFRPs, cross-linked with unsaturated polyesters or vinyl esters, to benzoic acid. The thermoset matrix is upgraded via biocatalysis utilizing an engineered strain of the filamentous fungus <i>Aspergillus nidulans</i>, which gives access to valuable secondary metabolites in high yields, exemplified here by (2<i>Z</i>,4<i>Z</i>,6<i>E</i>)-octa-2,4,6-trienoic acid. Reactions are engineered to preserve the carbon fibers with much of their sizing so that the isolated carbon fiber plies are manufactured into new composite coupons that exhibit mechanical properties comparable to those of virgin manufacturing substrates. In sum, this represents the first system to reclaim a high value from both the fiber fabric and polymer matrix of a CFRP.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30004–30008 30004–30008"},"PeriodicalIF":14.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanochemical Synthesis and Magnetic Properties of the Mixed-Valent Binary Silver(I,II) Fluorides, AgI2AgIIF4 and AgIAgIIF3","authors":"Matic Belak Vivod,&nbsp;Zvonko Jagličić,&nbsp;Graham King,&nbsp;Thomas C. Hansen,&nbsp;Matic Lozinšek and Mirela Dragomir*,&nbsp;","doi":"10.1021/jacs.4c1177210.1021/jacs.4c11772","DOIUrl":"https://doi.org/10.1021/jacs.4c11772https://doi.org/10.1021/jacs.4c11772","url":null,"abstract":"<p >Fluoridoargentates(II) represent a fascinating class of silver(II) compounds with structural and magnetic similarities to cuprate superconductors. However, their synthesis is challenging, leaving their properties largely underexplored and hindering the discovery of new phases. This study introduces mechanochemistry as a novel approach for the synthesis of fluoridoargentates(II), avoiding the use of anhydrous HF or elemental fluorine and employing readily available equipment. Notably, ball milling of commercially available precursors successfully produced the long-sought-after first two examples of binary mixed-valent silver(I,II) phases, Ag^I₂Ag^IIF₄ (Ag₃F₄) and Ag^IAg^IIF₃ (Ag₂F₃). While the Ag^I₂Ag^IIF₄ phase was obtained at room temperature, the Ag^IAg^IIF₃ phase is metastable and required milling under cryogenic conditions. Characterization by synchrotron powder X-ray and neutron diffraction revealed that Ag^I₂Ag^IIF₄ crystallizes in the <i>P</i>2₁/<i>c</i> space group and is isostructural to β-K₂AgF₄. In this crystal structure, [Ag^IIF₂F_4/2]^2– distorted octahedral units with 4 + 2 coordination, extend parallel to <i>a</i>-crystallographic axis giving a quasi-one-dimensional canted antiferromagnetic character, as shown by magnetic susceptibility. The triclinic perovskite Ag^IAg^IIF₃ phase adopts the <i>P</i>1̅ space group, is isostructural to AgCuF₃ and also shows features of a one-dimensional antiferromagnet. This mechanochemical approach, also successfully applied to synthesize β-K₂AgF₄, is expected to expand the field of silver(II) chemistry, accelerating the search for silver analogs to cuprate superconductors and potentially extending to other cations in unusual oxidation states.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30510–30517 30510–30517"},"PeriodicalIF":14.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacs.4c11772","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Alkyl(trimethylsilyl)amides: Substituent- and Solvent-dependent Solution Structures and Reactivities","authors":"Qiulin You,&nbsp;Yun Ma,&nbsp;Ryan A. Woltornist,&nbsp;Nathan M. Lui,&nbsp;Jesse A. Spivey,&nbsp;Ivan Keresztes and David B. Collum*,&nbsp;","doi":"10.1021/jacs.4c1083610.1021/jacs.4c10836","DOIUrl":"https://doi.org/10.1021/jacs.4c10836https://doi.org/10.1021/jacs.4c10836","url":null,"abstract":"<p >The preparation of sodium isopropyl(trimethylsilyl)amide (NaPTA), sodium (1-phenylethyl)(trimethylsilyl)amide (NaPETA), sodium <i>tert</i>-butyl(trimethylsilyl)amide (NaBTA), and isotopologues [¹⁵N]NaPTA and [¹⁵N]NaBTA are described. Solution structural studies using a combination of ²⁹Si NMR spectroscopy, the Method of Continuous Variations, and density functional theory computations provided insights into aggregation and solvation in a range of solvents including toluene, <i>N</i>,<i>N</i>-dimethylethylamine, triethylamine, MTBE, THF, 1,2-dimethoxyethane (DME), diglyme, <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylenediamine (TMEDA), <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylcyclohexanediamine (TMCDA), <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>″,<i>N</i>″-pentamethyldiethylenetriamine (PMDTA). 12-crown-4, 15-crown-5, and 18-crown-6 revealed solvent- and substituent-dependent dimer–monomer mixtures with affiliated solvation numbers. Complexation of the three crown ethers documented both crown and substituent dependencies. Qualitative studies of reactivity showed a variety of reactions of NaPETA. Aminolysis of methyl benzoate with dialkylamines mediated by NaPTA afforded high yields of benzamides. Quantitative rate studies of aminolysis of methyl benzoate by NaPTA revealed a 47,000-fold range of rates. Detailed rate studies in toluene and THF showed dimer-based mechanisms. The role of primary- and secondary-shell solvation by THF is discussed, including nuances of methods used to separate the two contributions. PMDTA-solvated NaPTA monomer reacts as a monomer whereas bis-diglyme solvated monomer reacts as a dimer. Rate studies exploring the structure–reactivity correlations of the three crown ethers show mono- and bis-crown-based pathways in which 15-crown-5─the crown ether often said to be of choice for sodium─was decidedly inferior as an accelerant.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30397–30421 30397–30421"},"PeriodicalIF":14.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nickel-Catalyzed Asymmetric (3 + 2) Annulations of Propargylic Carbonates and Vinylogous Donors via an Alkenylation Pathway","authors":"Zhi Zhao,&nbsp;Lei Zhu,&nbsp;Zhao-Li Song,&nbsp;Keji Qubi,&nbsp;Qin Ouyang*,&nbsp;Wei Du* and Ying-Chun Chen*,&nbsp;","doi":"10.1021/jacs.4c1266410.1021/jacs.4c12664","DOIUrl":"https://doi.org/10.1021/jacs.4c12664https://doi.org/10.1021/jacs.4c12664","url":null,"abstract":"<p >The transition-metal-catalyzed alkenylation strategy of propargylic alcohol derivatives provides an efficient protocol to access multifunctional products in a double-nucleophilic attack pattern. While limited relevant asymmetric examples have been reported via palladium catalysis, here we first demonstrate that a nonprecious Ni(0)-based chiral complex can efficiently promote the tandem substitution process between propargylic carbonates and <i>N</i>-trifluoroethyl ketimines via consecutive aza-vinylogous activations, finally accomplishing a (3 + 2) annulation reaction to afford products embedding a 4-methylene-3,4-dihydro-2<i>H</i>-pyrrole framework with high regio-, diastereo-, and enantiocontrol. Their assemblies with a few all-carbon-based vinylogous precursors are also successful, and enantioenriched adducts containing a 3-methylenecyclopentene scaffold are furnished effectively. The substitution patterns for both types of substrates are substantial, and an array of synthetic elaborations is conducted to deliver more versatile architectures with high application potential. In addition, density functional theory calculations and control experiments have been conducted to rationalize the catalytic pathways and regio- and enantioselectivity control.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30678–30685 30678–30685"},"PeriodicalIF":14.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating 19F Distance Restraints for Accurate Protein Structure Determination by Magic Angle Spinning NMR Spectroscopy","authors":"Brent R. Runge,&nbsp;Roman Zadorozhnyi,&nbsp;Caitlin M. Quinn,&nbsp;Ryan W. Russell,&nbsp;Manman Lu,&nbsp;Santiago Antolínez,&nbsp;Jochem Struppe,&nbsp;Charles D. Schwieters,&nbsp;In-Ja L. Byeon,&nbsp;Jodi A. Hadden-Perilla,&nbsp;Angela M. Gronenborn* and Tatyana Polenova*,&nbsp;","doi":"10.1021/jacs.4c1137310.1021/jacs.4c11373","DOIUrl":"https://doi.org/10.1021/jacs.4c11373https://doi.org/10.1021/jacs.4c11373","url":null,"abstract":"<p >Traditional protein structure determination by magic angle spinning (MAS) solid-state NMR spectroscopy primarily relies on interatomic distances up to 8 Å, extracted from ¹³C-, ¹⁵N-, and ¹H-based dipolar-based correlation experiments. Here, we show that ¹⁹F fast (60 kHz) MAS NMR spectroscopy can supply additional, longer distances. Using 4F-Trp,U-¹³C,¹⁵N crystalline <i>Oscillatoria agardhii</i> agglutinin (OAA), we demonstrate that judiciously designed 2D and 3D ¹⁹F-based dipolar correlation experiments such as (H)CF, (H)CHF, and FF can yield interatomic distances in the 8–16 Å range. Incorporation of fluorine-based restraints into structure calculation improved the precision of Trp side chain conformations as well as regions in the protein around the fluorine containing residues, with notable improvements observed for residues in proximity to the Trp pairs (W10/W17 and W77/W84) in the carbohydrate-binding loops, which lacked sufficient long-range ¹³C-¹³C distance restraints. Our work highlights the use of fluorine and ¹⁹F fast MAS NMR spectroscopy as a powerful structural biology tool.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30483–30494 30483–30494"},"PeriodicalIF":14.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective C–N Bond Cleavage in Unstrained Pyrrolidines Enabled by Lewis Acid and Photoredox Catalysis","authors":"Kazuhiro Aida,&nbsp;Marina Hirao,&nbsp;Tsuyoshi Saitoh,&nbsp;Takashi Yamamoto,&nbsp;Yasuaki Einaga,&nbsp;Eisuke Ota* and Junichiro Yamaguchi*,&nbsp;","doi":"10.1021/jacs.4c1321010.1021/jacs.4c13210","DOIUrl":"https://doi.org/10.1021/jacs.4c13210https://doi.org/10.1021/jacs.4c13210","url":null,"abstract":"<p >Cleavage of inert C–N bonds in unstrained azacycles such as pyrrolidine remains a formidable challenge in synthetic chemistry. To address this, we introduce an effective strategy for the reductive cleavage of the C–N bond in <i>N</i>-benzoyl pyrrolidine, leveraging a combination of Lewis acid and photoredox catalysis. This method involves single-electron transfer to the amide, followed by site-selective cleavage at the C2–N bond. Cyclic voltammetry and NMR studies demonstrated that the Lewis acid is crucial for promoting the single-electron transfer from the photoredox catalyst to the amide carbonyl group. This protocol is widely applicable to various pyrrolidine-containing molecules and enables inert C–N bond cleavage including C–C bond formation via intermolecular radical addition. Furthermore, the current protocol successfully converts pyrrolidines to aziridines, γ-lactones, and tetrahydrofurans, showcasing its potential of the inert C–N bond cleavage for expanding synthetic strategies.</p>","PeriodicalId":14,"journal":{"name":"ACS Combinatorial Science","volume":"146 44","pages":"30698–30707 30698–30707"},"PeriodicalIF":14.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacs.4c13210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}