Tellurium (Te), with its rich valence states (–2 to +6), could endow aqueous batteries with potentially high specific capacity. However, achieving complete and stable hypervalent Te0/Te4+ electrochemistry in an aqueous environment poses significant challenges, owing to the sluggish reduction kinetics, the easy dissolution of Te4+ species, and a controversial energy storage mechanism. Herein, for the first time, we demonstrate an amorphous strategy for robust aqueous TeO2/Te electrochemistry. With strong hydrogen bonding, NH4Ac confines free water, prompting TeO2 amorphous (a-TeO2). In-situ synchrotron characterization, spectroscopy analysis, electrochemical evaluation, and theoretical calculations reveal a specific 4 e− solid-solid transition pathway (Te to a-TeO2) with accelerated diffusion and charge transfer kinetics, attributed to a closer unoccupied electron orbital to the Fermi level and a reduced water desorption energy barrier in a-TeO2. Impressively, the a-TeO2/Te electrochemistry exhibits a high reversible capacity of 834 mAh g−1 (99% of Te redox utilization), superior rate performance (644 mAh g−1 at 10 A g−1), and an ultralong lifespan (over 3000 cycles). These findings prove a new tactic to advance aqueous Te electrochemistry toward high-energy aqueous batteries.
{"title":"Amorphization Stabilizes Te-based Aqueous Batteries via Confining Free Water","authors":"Yanyan Zhang, Wanhai Zhou, Boya Wang, Tengsheng Zhang, Xiaoyu Yu, Xinran Li, Gaoyang Li, Hongrun Jin, Minghua Chen, Wei Li, Dongyuan Zhao, Xin Liu, Dongliang Chao","doi":"10.1002/anie.202424056","DOIUrl":"https://doi.org/10.1002/anie.202424056","url":null,"abstract":"Tellurium (Te), with its rich valence states (–2 to +6), could endow aqueous batteries with potentially high specific capacity. However, achieving complete and stable hypervalent Te0/Te4+ electrochemistry in an aqueous environment poses significant challenges, owing to the sluggish reduction kinetics, the easy dissolution of Te4+ species, and a controversial energy storage mechanism. Herein, for the first time, we demonstrate an amorphous strategy for robust aqueous TeO2/Te electrochemistry. With strong hydrogen bonding, NH4Ac confines free water, prompting TeO2 amorphous (a-TeO2). In-situ synchrotron characterization, spectroscopy analysis, electrochemical evaluation, and theoretical calculations reveal a specific 4 e− solid-solid transition pathway (Te to a-TeO2) with accelerated diffusion and charge transfer kinetics, attributed to a closer unoccupied electron orbital to the Fermi level and a reduced water desorption energy barrier in a-TeO2. Impressively, the a-TeO2/Te electrochemistry exhibits a high reversible capacity of 834 mAh g−1 (99% of Te redox utilization), superior rate performance (644 mAh g−1 at 10 A g−1), and an ultralong lifespan (over 3000 cycles). These findings prove a new tactic to advance aqueous Te electrochemistry toward high-energy aqueous batteries.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"28 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975097","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}
Solid-state nanopore is a promising single molecular detection technique, but is largely limited by relatively low resolution to small-size targets and laborious design of signaling probes. Here we establish a universal, CRISPR/Cas-Assisted Nanopore Operational Nexus (CANON), which can accurately transduce different targeting sources/species into different DNA structural probes via a “Signal-ON” mode. Target recognition activates the cleavage activity of a Cas12a/crRNA system and then completely digest the blocker of an initiator. The unblocked initiator then triggers downstream DNA assembly reaction and generate a large-size structure easy for nanopore detection. Such integration of Cas12a/crRNA with DNA assembly establishes an accurate correspondence among the input targets, output DNA structures, and the ultimate nanopore signals. We demonstrated dsDNA, long RNA (i.e., Flu virus gene), short microRNA (i.e., let-7d) and non-nucleic acids (i.e., Pb2+) as input paradigms. Various structural assembly reactions, such as hybridization chain reaction (HCR), G-HCR and duplex polymerization strategy (DPS), are adapted as outputs for nanopore signaling. Simultaneous assay is also verified via transferring FluA and FluB genes into HCR and G-HCR, respectively. CANON is thus a modular sensing platform holding multiple advantages such as high accuracy, high resolution and high universality, which can be easily customized into various application scenes.
{"title":"Accurate Molecular Sensing based on a Modular and Customizable CRISPR/Cas-Assisted Nanopore Operational Nexus (CANON)","authors":"Huaning Wang, Rujian Zhao, Bing Zhang, Yao Xiao, Chunmiao Yu, Yesheng Wang, Chunxu Yu, Yidan Tang, Yanru Li, Baiyang Lu, Bingling Li","doi":"10.1002/anie.202423473","DOIUrl":"https://doi.org/10.1002/anie.202423473","url":null,"abstract":"Solid-state nanopore is a promising single molecular detection technique, but is largely limited by relatively low resolution to small-size targets and laborious design of signaling probes. Here we establish a universal, CRISPR/Cas-Assisted Nanopore Operational Nexus (CANON), which can accurately transduce different targeting sources/species into different DNA structural probes via a “Signal-ON” mode. Target recognition activates the cleavage activity of a Cas12a/crRNA system and then completely digest the blocker of an initiator. The unblocked initiator then triggers downstream DNA assembly reaction and generate a large-size structure easy for nanopore detection. Such integration of Cas12a/crRNA with DNA assembly establishes an accurate correspondence among the input targets, output DNA structures, and the ultimate nanopore signals. We demonstrated dsDNA, long RNA (i.e., Flu virus gene), short microRNA (i.e., let-7d) and non-nucleic acids (i.e., Pb2+) as input paradigms. Various structural assembly reactions, such as hybridization chain reaction (HCR), G-HCR and duplex polymerization strategy (DPS), are adapted as outputs for nanopore signaling. Simultaneous assay is also verified via transferring FluA and FluB genes into HCR and G-HCR, respectively. CANON is thus a modular sensing platform holding multiple advantages such as high accuracy, high resolution and high universality, which can be easily customized into various application scenes.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"4 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968343","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}
Electrocatalytic transfer alkyne semi-hydrogenation with H2O as hydrogen source is industrially promising for selective electrosynthesis of high value-added alkenes while inhibiting byproduct alkanes. Although great achievements, their development has remarkably restricted by designing atomically sophisticated electrocatalysts. Here, we reported single-crystalline mesoporous copper nanoplates (meso-Cu PLs) as a robust yet highly efficient electrocatalyst for selective alkene electrosynthesis from transfer semi-hydrogenation reaction of alkyne in H2O. Anisotropic meso-Cu PLs were prepared through a facile epitaxial growth strategy with functional C22H45N(CH3)2-C3H6-SH as concurrent mesopore-forming and structure-controlled surfactant. Different to nonporous Cu counterparts with flat surface, meso-Cu PLs exposed abundant Cu+ sites, which not only stabilized active H* radicals from electrocatalytic H2O splitting without coupling into molecular H2 but also accelerated kinetically the desorption of semi-hydrogenated alkenes. With 4-aminophenylacetylene (4-AP) as the substrate, anisotropic meso-Cu PLs delivered superior electrocatalytic transfer semi-hydrogenation performance with up to 99% of 4-aminostyrene (4-AS) selectivity and 100% of 4-AP conversion as well as good cycle stability (6 cycles). Meanwhile, meso-Cu PLs were electrocatalytically applicable for transfer semi-hydrogenation of various alkynes. This work paved an alternative paradigm for designing robust mesoporous metal electrocatalysts with structurally functional metal sites applied in the selective electrosynthesis of industrially value-added chemicals in H2O.
{"title":"Mesoporous Cu Nanoplates with Exposed Cu+ Sites for Efficient Electrocatalytic Transfer Semi-Hydrogenation of Alkynes","authors":"Hao Lv, Lizhi Sun, Deqing Tang, Ben Liu","doi":"10.1002/anie.202423112","DOIUrl":"https://doi.org/10.1002/anie.202423112","url":null,"abstract":"Electrocatalytic transfer alkyne semi-hydrogenation with H2O as hydrogen source is industrially promising for selective electrosynthesis of high value-added alkenes while inhibiting byproduct alkanes. Although great achievements, their development has remarkably restricted by designing atomically sophisticated electrocatalysts. Here, we reported single-crystalline mesoporous copper nanoplates (meso-Cu PLs) as a robust yet highly efficient electrocatalyst for selective alkene electrosynthesis from transfer semi-hydrogenation reaction of alkyne in H2O. Anisotropic meso-Cu PLs were prepared through a facile epitaxial growth strategy with functional C22H45N(CH3)2-C3H6-SH as concurrent mesopore-forming and structure-controlled surfactant. Different to nonporous Cu counterparts with flat surface, meso-Cu PLs exposed abundant Cu+ sites, which not only stabilized active H* radicals from electrocatalytic H2O splitting without coupling into molecular H2 but also accelerated kinetically the desorption of semi-hydrogenated alkenes. With 4-aminophenylacetylene (4-AP) as the substrate, anisotropic meso-Cu PLs delivered superior electrocatalytic transfer semi-hydrogenation performance with up to 99% of 4-aminostyrene (4-AS) selectivity and 100% of 4-AP conversion as well as good cycle stability (6 cycles). Meanwhile, meso-Cu PLs were electrocatalytically applicable for transfer semi-hydrogenation of various alkynes. This work paved an alternative paradigm for designing robust mesoporous metal electrocatalysts with structurally functional metal sites applied in the selective electrosynthesis of industrially value-added chemicals in H2O.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"84 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968615","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}
Yaning Xu, Shiyan Ai, Tiantian Wu, Chengxu Zhou, Qing Huang, Baiyan Li, Dan Tian, Xian-He Bu
Efficient utilization of solar energy is widely regarded as a crucial solution to addressing the energy crisis and reducing reliance on fossil fuels. Coupling photothermal and photochemical conversion can effectively improve solar energy utilization yet remains challenging. Here, inspired by the photosynthesis system in green plants, we report herein an artificial solar energy converter (ASEC) composed of light‐harvesting units as solar collector and oriented ionic hydrophilic channels as reactors and transporters. Based on such architecture, the obtained ASEC (namely ASEC‐NJFU‐1) can efficiently realize parallel production of freshwater and H2O2 from natural seawater under natural light. The total solar energy conversion (SEC) of ASEC‐NJFU‐1 reaches up to 8047 kJ m‐2 h‐1, corresponding to production rates of freshwater and H2O2 are 3.56 kg m‐2 h‐1 and 19 mM m‐2 h‐1, respectively, which is a record‐high value among all photothermal‐photocatalytic systems reported to date. Mechanism investigation of combining spectrum and experimental studies indicated that the high SEC performance for ASEC‐NJFU‐1 was attributed to the presence of plant bioinspired architecture with carbon nanotubes as solar‐harvestor and COF‐based oriented aerogel as reactors and transporters. Our work thus establishes a novel artificial photosynthesis system for highly efficient solar energy utilization.
{"title":"Bioinspired Photo‐Thermal Catalytic System using Covalent Organic Framework‐based Aerogel for Synchronous Seawater Desalination and H2O2 Production","authors":"Yaning Xu, Shiyan Ai, Tiantian Wu, Chengxu Zhou, Qing Huang, Baiyan Li, Dan Tian, Xian-He Bu","doi":"10.1002/anie.202421990","DOIUrl":"https://doi.org/10.1002/anie.202421990","url":null,"abstract":"Efficient utilization of solar energy is widely regarded as a crucial solution to addressing the energy crisis and reducing reliance on fossil fuels. Coupling photothermal and photochemical conversion can effectively improve solar energy utilization yet remains challenging. Here, inspired by the photosynthesis system in green plants, we report herein an artificial solar energy converter (ASEC) composed of light‐harvesting units as solar collector and oriented ionic hydrophilic channels as reactors and transporters. Based on such architecture, the obtained ASEC (namely ASEC‐NJFU‐1) can efficiently realize parallel production of freshwater and H2O2 from natural seawater under natural light. The total solar energy conversion (SEC) of ASEC‐NJFU‐1 reaches up to 8047 kJ m‐2 h‐1, corresponding to production rates of freshwater and H2O2 are 3.56 kg m‐2 h‐1 and 19 mM m‐2 h‐1, respectively, which is a record‐high value among all photothermal‐photocatalytic systems reported to date. Mechanism investigation of combining spectrum and experimental studies indicated that the high SEC performance for ASEC‐NJFU‐1 was attributed to the presence of plant bioinspired architecture with carbon nanotubes as solar‐harvestor and COF‐based oriented aerogel as reactors and transporters. Our work thus establishes a novel artificial photosynthesis system for highly efficient solar energy utilization.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"21 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968178","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}
Yu Zheng, Lin-Lin Teng, Ting-Ting Zhou, Zhi-Wei Liu, Kai Guo, Hao Li, Tao Li, Liang-Liang Wang, Yan Liu, Sheng-Hong Li
Plant sesterterpenoids are an extremely rare family of natural products that generally possess novel chemical structures and diverse biological activities. Here, we report the discovery of an unprecedented group of minor plant sesterterpenoids, gracilisoids B-E (2-5), which feature two types of highly functionalized bicyclo[3.2.0]heptane carbon skeletons, along with their biogenetically-related precursor gracilisoid A (1), from a Lamiaceae ethnomedicinal plant, Eurysolen gracilis. To confirm their structures and obtain adequate materials for biological research, the asymmetric total syntheses of gracilisoids A-E (1-5) and four new biogenetically-related congeners gracilisoids F-I (6-9) were achieved from commercially available (−)-citronellal via a bioinspired approach that involves a Norrish-Yang photocyclization/α-hydroxy ketone rearrangement tandem reaction and a late-stage biomimetic photo-oxidation as key steps. Biological investigations revealed that gracilisoids A-I (1-9) significantly inhibited IFN-γ production and/or T cell proliferation probably via inhibition of the STAT pathway. The findings herald the potential of these gracilisoids as novel immunosuppressive agents, and the efficient synthetic approaches will facilitate a comprehensive evaluation of their value in future drug development.
{"title":"Discovery and Total Synthesis of a New Class of Minor Immunosuppressive Plant Sesterterpenoids","authors":"Yu Zheng, Lin-Lin Teng, Ting-Ting Zhou, Zhi-Wei Liu, Kai Guo, Hao Li, Tao Li, Liang-Liang Wang, Yan Liu, Sheng-Hong Li","doi":"10.1002/anie.202421497","DOIUrl":"https://doi.org/10.1002/anie.202421497","url":null,"abstract":"Plant sesterterpenoids are an extremely rare family of natural products that generally possess novel chemical structures and diverse biological activities. Here, we report the discovery of an unprecedented group of minor plant sesterterpenoids, gracilisoids B-E (2-5), which feature two types of highly functionalized bicyclo[3.2.0]heptane carbon skeletons, along with their biogenetically-related precursor gracilisoid A (1), from a Lamiaceae ethnomedicinal plant, Eurysolen gracilis. To confirm their structures and obtain adequate materials for biological research, the asymmetric total syntheses of gracilisoids A-E (1-5) and four new biogenetically-related congeners gracilisoids F-I (6-9) were achieved from commercially available (−)-citronellal via a bioinspired approach that involves a Norrish-Yang photocyclization/α-hydroxy ketone rearrangement tandem reaction and a late-stage biomimetic photo-oxidation as key steps. Biological investigations revealed that gracilisoids A-I (1-9) significantly inhibited IFN-γ production and/or T cell proliferation probably via inhibition of the STAT pathway. The findings herald the potential of these gracilisoids as novel immunosuppressive agents, and the efficient synthetic approaches will facilitate a comprehensive evaluation of their value in future drug development.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"88 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968486","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}
Zhiyong Wang, Hio-Ieng Un, Tsai-Jung Liu, Baokun Liang, Miroslav Polozij, Mike Hambsch, Jonas F. Pöhls, R. Thomas Weitz, Stefan C. B. Mannsfeld, Ute Kaiser, Thomas Heine, Henning Sirringhaus, Xinliang Feng, Renhao Dong
Electrically conductive coordination polymers (ECCPs), particularly those incorporating benzenehexathiol (BHT) ligands, are emerging as a distinctive class of electronic materials with tunable semiconducting and metallic properties. However, the exploration of novel ECCPs with low‐symmetry structures and electrical anisotropy remains under development. Here, we report the on‐water surface synthesis of a novel ECCP, namely Cu5BHT, which exhibits a low‐symmetry structure and unique in‐plane electrical anisotropy that differs from the well‐known Cu3BHT phase. Utilizing imaging and diffraction techniques, we elucidate the unit cell and crystal structure of Cu5BHT, revealing an asymmetric arrangement of the kagome resembling lattice connected by two different secondary building units: square planar CuS4 and non‐planar Cu2S4. Theoretical studies indicate that Cu5BHT is metallic and exhibits in‐plane electrical anisotropy due to the structure arranged in interconnected well‐conducting CuS4 chains and less‐conducting Cu2S4 slabs oriented along single crystal direction. Single‐crystal electrical measurements confirm a metallic character characterized by the increase of conductance upon cooling. Notably, the measured conductance along different crystal directions within the ab plane unambiguously reveals a significant anisotropy, with an anisotropic factor reaching ~8. This work demonstrates a novel low‐symmetry ECCP and highlights its potential for achieving in‐plane electrical anisotropy.
{"title":"A Low‐Symmetry Copper Benzenehexathiol Coordination Polymer with In‐Plane Electrical Anisotropy","authors":"Zhiyong Wang, Hio-Ieng Un, Tsai-Jung Liu, Baokun Liang, Miroslav Polozij, Mike Hambsch, Jonas F. Pöhls, R. Thomas Weitz, Stefan C. B. Mannsfeld, Ute Kaiser, Thomas Heine, Henning Sirringhaus, Xinliang Feng, Renhao Dong","doi":"10.1002/anie.202423341","DOIUrl":"https://doi.org/10.1002/anie.202423341","url":null,"abstract":"Electrically conductive coordination polymers (ECCPs), particularly those incorporating benzenehexathiol (BHT) ligands, are emerging as a distinctive class of electronic materials with tunable semiconducting and metallic properties. However, the exploration of novel ECCPs with low‐symmetry structures and electrical anisotropy remains under development. Here, we report the on‐water surface synthesis of a novel ECCP, namely Cu5BHT, which exhibits a low‐symmetry structure and unique in‐plane electrical anisotropy that differs from the well‐known Cu3BHT phase. Utilizing imaging and diffraction techniques, we elucidate the unit cell and crystal structure of Cu5BHT, revealing an asymmetric arrangement of the kagome resembling lattice connected by two different secondary building units: square planar CuS4 and non‐planar Cu2S4. Theoretical studies indicate that Cu5BHT is metallic and exhibits in‐plane electrical anisotropy due to the structure arranged in interconnected well‐conducting CuS4 chains and less‐conducting Cu2S4 slabs oriented along single crystal direction. Single‐crystal electrical measurements confirm a metallic character characterized by the increase of conductance upon cooling. Notably, the measured conductance along different crystal directions within the ab plane unambiguously reveals a significant anisotropy, with an anisotropic factor reaching ~8. This work demonstrates a novel low‐symmetry ECCP and highlights its potential for achieving in‐plane electrical anisotropy.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"29 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968179","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}
Yanan Gao, Qingjie Bai, Youxiao Ren, Xintian Shao, Mengrui Zhang, Luling Wu, Simon Lewis, Tony James, Xiaoyuan Chen, Qixin Chen
Mitophagy that disrupt mitochondrial membrane potential (MMP), represents a critical focus in pharmacology. However, the discovery and evaluation of MMP‐disrupting drugs are often hampered using commercially available marker molecules that target similar or identical zones. These markers can significantly interfere with, obscure, or amplify the functional effects of MMP‐targeting drugs, frequently leading to clinical failures. In response to this challenge, we propose a “one‐two punch” drug design strategy that integrates both target‐zone drug functionality and non‐target zone biological reporting within a single small‐molecule drug. We have developed a novel mitophagy self‐check drug (MitoSC) that exhibits dual‐color and dual‐localization properties. The functional component of this system is a variable MitoSC that disrupts MMP homeostasis, thereby inducing mitophagy. Upon activation, this component transforms into a blue‐fluorescent monomer (MitoSC‐fun) specifically within the mitochondrial target zone. The biological reporting component is represented by a red‐fluorescent monomer (MitoSC‐rep) that localizes to lysosomes, the non‐target zone. As mitophagy progresses, the fluorescent signals from MitoSC‐rep (lysosomes) and MitoSC‐fun (mitochondria) converge, enabling real‐time monitoring of the mitophagy process. Our findings underscore the potential of a single‐molecule drug to exert target‐zone specific actions while simultaneously providing non‐target zone self‐checking, offering a new perspective for drug design.
{"title":"A Small‐Molecule Drug for the Self‐Checking of Mitophagy","authors":"Yanan Gao, Qingjie Bai, Youxiao Ren, Xintian Shao, Mengrui Zhang, Luling Wu, Simon Lewis, Tony James, Xiaoyuan Chen, Qixin Chen","doi":"10.1002/anie.202421269","DOIUrl":"https://doi.org/10.1002/anie.202421269","url":null,"abstract":"Mitophagy that disrupt mitochondrial membrane potential (MMP), represents a critical focus in pharmacology. However, the discovery and evaluation of MMP‐disrupting drugs are often hampered using commercially available marker molecules that target similar or identical zones. These markers can significantly interfere with, obscure, or amplify the functional effects of MMP‐targeting drugs, frequently leading to clinical failures. In response to this challenge, we propose a “one‐two punch” drug design strategy that integrates both target‐zone drug functionality and non‐target zone biological reporting within a single small‐molecule drug. We have developed a novel mitophagy self‐check drug (MitoSC) that exhibits dual‐color and dual‐localization properties. The functional component of this system is a variable MitoSC that disrupts MMP homeostasis, thereby inducing mitophagy. Upon activation, this component transforms into a blue‐fluorescent monomer (MitoSC‐fun) specifically within the mitochondrial target zone. The biological reporting component is represented by a red‐fluorescent monomer (MitoSC‐rep) that localizes to lysosomes, the non‐target zone. As mitophagy progresses, the fluorescent signals from MitoSC‐rep (lysosomes) and MitoSC‐fun (mitochondria) converge, enabling real‐time monitoring of the mitophagy process. Our findings underscore the potential of a single‐molecule drug to exert target‐zone specific actions while simultaneously providing non‐target zone self‐checking, offering a new perspective for drug design.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968204","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}
Pedro Montes-Tolentino, Alexander S. Mikherdov, Christoph Drechsler, Julian J. Holstein, Guido H. Clever
Precise control over the catenation process in interlocked supramolecular systems remains a significant challenge. Here, we report a system in which a lantern-shaped Pd2L4 cage can dimerize to form two distinct Pd4L8 catenanes with different interlocking degree: a previously described quadruply interlocked double cage motif of D4 symmetry and an unprecedented triply interlocked structure of C2h symmetry. While the former structure features a linear arrangement of four Pd(II) centers, separated by three mechanically linked pockets, the new motif has a staggered shape. Both assemblies are topological isomers, coexisting in equilibrium in solution. The triply interlocked species is thermodynamically more stable due to extended noncovalent interactions between the ligands, as supported by X-ray structure analysis and electronic structure calculations. Notably, the degree of interlocking in the double cage system can be controlled by a change of temperature and through anion exchange. Cage-to-cage transformations were followed by NMR, MS and TIMS methods.
{"title":"Control of Interlocking Mode in Pd4L8 Cage Catenanes","authors":"Pedro Montes-Tolentino, Alexander S. Mikherdov, Christoph Drechsler, Julian J. Holstein, Guido H. Clever","doi":"10.1002/anie.202423810","DOIUrl":"https://doi.org/10.1002/anie.202423810","url":null,"abstract":"Precise control over the catenation process in interlocked supramolecular systems remains a significant challenge. Here, we report a system in which a lantern-shaped Pd2L4 cage can dimerize to form two distinct Pd4L8 catenanes with different interlocking degree: a previously described quadruply interlocked double cage motif of D4 symmetry and an unprecedented triply interlocked structure of C2h symmetry. While the former structure features a linear arrangement of four Pd(II) centers, separated by three mechanically linked pockets, the new motif has a staggered shape. Both assemblies are topological isomers, coexisting in equilibrium in solution. The triply interlocked species is thermodynamically more stable due to extended noncovalent interactions between the ligands, as supported by X-ray structure analysis and electronic structure calculations. Notably, the degree of interlocking in the double cage system can be controlled by a change of temperature and through anion exchange. Cage-to-cage transformations were followed by NMR, MS and TIMS methods.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"43 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968487","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}
Isotope Exchange processes are becoming the preferred way to prepare isotopically labelled molecules, avoiding the redesign of multistep synthetic protocols. In the case of deuterium incorporation, the most used strategy has employed transition metals, that offer high reactivity under mild reaction conditions. Despite their success, the trade-off is that these metals are precious, and often exhibit high toxicity. Therefore, alternative protocols using earth abundant catalysts would be a welcome addition to this field. Here, we show how the simple bases NaHMDS (HMDS = hexamethyldisilazide) and NaCH2SiMe3 can efficiently and selectively promote deuteration of a wide range of C(sp2)–H and C(sp3)–H bonds in DMSO-d6, providing an easy and direct access to deuterated compounds. Heterocycles, fluoroarenes, N-heterocyclic carbenes, amides and other aromatic molecules could be deuterated under mild conditions using catalytic amounts of base. Mechanistic studies have flagged up the importance of the metalated substrate and metalated solvent in solution, establishing an equilibrium between these compounds, which is crucial for the success of this approach. An alkali-metal effect was observed, with heavier alkali-metal amides being more reactive at room temperature, but their lower stability at higher temperatures made sodium bases the optimal reagents for Hydrogen Isotope Exchange.
{"title":"Selective Hydrogen Isotope Exchange Catalysed by Simple Alkali-Metal Bases in DMSO","authors":"Melina Tschopp, Andreu Tortajada, Eva Hevia","doi":"10.1002/anie.202421736","DOIUrl":"https://doi.org/10.1002/anie.202421736","url":null,"abstract":"Isotope Exchange processes are becoming the preferred way to prepare isotopically labelled molecules, avoiding the redesign of multistep synthetic protocols. In the case of deuterium incorporation, the most used strategy has employed transition metals, that offer high reactivity under mild reaction conditions. Despite their success, the trade-off is that these metals are precious, and often exhibit high toxicity. Therefore, alternative protocols using earth abundant catalysts would be a welcome addition to this field. Here, we show how the simple bases NaHMDS (HMDS = hexamethyldisilazide) and NaCH2SiMe3 can efficiently and selectively promote deuteration of a wide range of C(sp2)–H and C(sp3)–H bonds in DMSO-d6, providing an easy and direct access to deuterated compounds. Heterocycles, fluoroarenes, N-heterocyclic carbenes, amides and other aromatic molecules could be deuterated under mild conditions using catalytic amounts of base. Mechanistic studies have flagged up the importance of the metalated substrate and metalated solvent in solution, establishing an equilibrium between these compounds, which is crucial for the success of this approach. An alkali-metal effect was observed, with heavier alkali-metal amides being more reactive at room temperature, but their lower stability at higher temperatures made sodium bases the optimal reagents for Hydrogen Isotope Exchange.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"22 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968480","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}
Huihui He, Ji Li, Jiayi Zhuang, Jinyi Huang, Yuxuan Meng, Xi Lin, Zhangwen Wei, Liangliang Zhang, Yu Fang, Mei Pan
Immobilizing organic chromophores within the rigid framework of metal‐organic frameworks (MOFs) augments fluorescence by effectively curtailing molecular motions. Yet, the substantial interspaces and free volumes inherent to MOFs can undermine photoluminescence efficiency, as they partially constrain intramolecular dynamics. In this study, we achieved optimization of both one‐ and two‐photon excited fluorescence by incorporating linkers into an interpenetrated tetraphenylethene‐based MOF (TPE‐MOF). This linker installation strategy enables fine‐tuning of both crystal packing density and ligand conformations. Strikingly, the desolvated MOFs exhibit remarkable two‐photon absorption (TPA) cross‐sections, reaching an impressive 8801 GM. Consequently, these materials demonstrate exceptional performance in one‐ and two‐photon excited cellular imaging of HepG2 cells. Our work introduces an innovative approach to enhancing two‐photon excited fluorescence (TPEF) and broadens the scope of research into one‐ and two‐photon excited fluorescence (1/2 PEF).
{"title":"Boosting One‐ and Two‐Photon Excited Fluorescence of Interpenetrated Tetraphenylethene‐Based Metal‐Organic Frameworks (TPE‐MOFs) by Linker Installation","authors":"Huihui He, Ji Li, Jiayi Zhuang, Jinyi Huang, Yuxuan Meng, Xi Lin, Zhangwen Wei, Liangliang Zhang, Yu Fang, Mei Pan","doi":"10.1002/anie.202420912","DOIUrl":"https://doi.org/10.1002/anie.202420912","url":null,"abstract":"Immobilizing organic chromophores within the rigid framework of metal‐organic frameworks (MOFs) augments fluorescence by effectively curtailing molecular motions. Yet, the substantial interspaces and free volumes inherent to MOFs can undermine photoluminescence efficiency, as they partially constrain intramolecular dynamics. In this study, we achieved optimization of both one‐ and two‐photon excited fluorescence by incorporating linkers into an interpenetrated tetraphenylethene‐based MOF (TPE‐MOF). This linker installation strategy enables fine‐tuning of both crystal packing density and ligand conformations. Strikingly, the desolvated MOFs exhibit remarkable two‐photon absorption (TPA) cross‐sections, reaching an impressive 8801 GM. Consequently, these materials demonstrate exceptional performance in one‐ and two‐photon excited cellular imaging of HepG2 cells. Our work introduces an innovative approach to enhancing two‐photon excited fluorescence (TPEF) and broadens the scope of research into one‐ and two‐photon excited fluorescence (1/2 PEF).","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"36 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968206","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}
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