Angewandte Chemie International Edition最新文献

{"title":"The ATM Kinase Inhibitor AZD0156 is a Potent Inhibitor of Plasmodium Phosphatidylinositol 4‐Kinase (PI4Kβ) and is an Attractive Candidate for Medicinal Chemistry Optimisation Ag…","authors":"John G. Woodland, Dina Coertzen, Kathryn J. Wicht, Virginia Franco Hidalgo, Charisse Flerida A. Pasaje, Luiz C. Godoy, Tarrick Qahash, Mmakwena M. Mmonwa, Godwin A. Dziwornu, Lynn Wambua, Sarah Harries, Constance M. Korkor, Mathew Njoroge, Liezl Gibhard, Dale Taylor, Meta Leshabane, Henrico Langeveld, Tayla Rabie, Janette Reader, Mariëtte van der Watt, Nelius Venter, Erica Erlank, Ayesha S. Aswat, Lizette L. Koekemoer, Tomas Yeo, Jin H. Jeon, David A. Fidock, Francisco Javier Gamo, Sergio Wittlin, Jacquin C. Niles, Manuel Llinas, Lauren B. Coulson, Lyn-Marié Birkholtz, Kelly Chibale","doi":"10.1002/anie.202425206","DOIUrl":"https://doi.org/10.1002/anie.202425206","url":null,"abstract":"New compounds targeting human malaria parasites are critical for effective malaria control and elimination. Here, we pursued the imidazoquinolinone AZD0156 (MMV1580483), a human ataxia‐telangiectasia mutated (ATM) kinase inhibitor that completed Phase I clinical trials as an anticancer agent. We validated its in vitro activity against the two main forms of the Plasmodium falciparum parasite in the human host, viz. the asexual blood (symptomatic) stage and sexual gametocyte (transmission) stage. Resistance selection, cross‐resistance, biochemical and conditional knockdown studies revealed that AZD0156 inhibits P. falciparum phosphatidylinositol 4‐kinase type III beta (PfPI4Kβ), a clinically‐validated target for the treatment of malaria. Metabolic perturbations, fixed‐ratio isobolograms, killing kinetics and morphological evaluation correlated AZD0156 inhibition with other known PI4Kβ inhibitors. The compound showed favourable in vivo pharmacokinetic properties and 81% antimalarial efficacy (4 x 50 mg/kg) in a P. berghei mouse malaria infection model. Importantly, a cleaner biochemical profile was measured against human kinases (MAP4K4, MINK1) implicated in embryofoetal developmental toxicity associated with the PfPI4Kβ inhibitor MMV390048. This improved kinase selectivity profile and structural differentiation from other PI4Kβ inhibitors, together with its multistage antiplasmodial activity and favourable pharmacokinetic properties, makes AZD0156 an attractive candidate for target‐based drug repositioning against malaria via a medicinal chemistry optimisation approach.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"118 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903025","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":"Kira Astakhova","authors":"Kira Astakhova","doi":"10.1002/anie.202508695","DOIUrl":"https://doi.org/10.1002/anie.202508695","url":null,"abstract":"“<i>The research project in my group that I am most excited about is RNA aptamer-drug conjugates—it merges chemistry, biology, and therapeutic innovation… My biggest inspiration is all my former supervisors and mentors—for their brilliance, integrity, and commitment to science</i>…”","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"45 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901723","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":"Charge Relocation Enables a Modular and Diastereoselective Synthesis of cis‐Substituted Tetrahydrofurans","authors":"Zhi-Jie Niu, Bogdan R. Brutiu, Margaux Riomet, Daniel Kaiser, Nuno Maulide","doi":"10.1002/anie.202503750","DOIUrl":"https://doi.org/10.1002/anie.202503750","url":null,"abstract":"Diastereoselective construction of organic scaffolds from simple and commercial materials is a powerful strategy in contemporary organic synthesis. Herein, we report a novel disconnection for the direct preparation of tetrahydrofurans (THF) and corresponding derivatives from acyl chlorides and alkenes using charge relocation. Newly synthesised Hantzsch ester derivatives, functioning both as hydride sources and selectivity modulators, enabled exceptional diastereoselectivity. The wide range of alkenes tolerated is a highlight of the method, enabling the construction of structurally distinct THF‐containing skeletons.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"11 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901620","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":"Supramolecular Charge‐Transfer Approach for Tunable and Efficient Circularly Polarized Delayed Fluorescence and Phosphorescence","authors":"Swadhin Garain, Anju Ajayan Kongasseri, Sopan M. Wagalgave, Rishika Konar, Darshana Deb, K. S. Narayan, Pralok K. Samanta, Subi J. George","doi":"10.1002/anie.202501330","DOIUrl":"https://doi.org/10.1002/anie.202501330","url":null,"abstract":"Achieving efficient circularly polarized luminescence (CPL) with a high luminescence dissymmetry factor (|glum|) in purely organic systems is a vibrant and rapidly evolving field of research. Recently, the growing interest in ambient organic phosphors has offered a promising alternative for achieving CPL with remarkable quantum yields by utilizing triplet states. While supramolecular charge‐transfer (CT) interactions are well‐established to improve |glum| by enhancing magnetic transition dipole components, their application to triplet‐harvesting organic systems remains unexplored. In this context, our current work introduces a supramolecular strategy to achieve highly efficient and tunable circularly polarized thermally activated delayed fluorescence (TADF) and phosphorescence by the involvement of intermolecular triplet CT states. Through‐space intermolecular CT interactions between heavy atom‐substituted bis‐chromophoric pyromellitic diimides (acceptors) and achiral phenyl carbazole derivatives (donors) enable one of the most efficient circularly polarized delayed luminescent systems, characterized by a high quantum yield (~46%) and a significant |glum| ~ 3.6 × 10⁻². Additionally, the modularity of this non‐covalent design allows for the tuning of emission from the orange to deep‐red regions by incorporating various donors. The strategy presented here opens new avenues for designing efficient CPL‐active organic phosphors.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"8 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901622","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":"Construction of Shamrock‐Shaped Giant Molecule Acceptors for Efficient Organic Solar Cells","authors":"Shengjie Xu, Qixin He, Xiaonan Xue, Jiawei Deng, Fei Han, Fei Xie, Xuechen Jiao, Libo Zhou, Rui Zeng, Zaiyu Wang, Ming Zhang, Lei Zhu, Hao Jing, Yongming Zhang, Feng Liu","doi":"10.1002/anie.202507616","DOIUrl":"https://doi.org/10.1002/anie.202507616","url":null,"abstract":"The discovery of non‐fullerene small molecule acceptor materials has breathed new development in organic solar cells (OSCs). However, it has also introduced the issue of insufficient device stability. Enhancing the glass transition temperature (Tg) of materials by connecting small molecules into giant molecules, thereby improving morphological stability, represents an effective material design strategy to address this issue. In this work, we have synthesized the shamrock‐shaped giant molecule materials T‐Qx based on high efficiency Qx‐series small molecule materials. Through systematically modulating the terminal and the central halogen atoms, precise control of the molecular conformation can be achieved. Notably, the fully chlorine‐substituted giant molecule T‐Qx‐15Cl exhibits the largest torsion angle of approximately 40° and achieves the highest Tg (up to 188°C) among these new materials. Photovoltaic devices based on these giant molecules demonstrate a low non‐radiative energy loss of approximately 0.21 eV, which results in a high open‐circuit voltage (Voc) above 0.93 V. T‐Qx‐15Cl presents the strongest interaction with the polymer donor PM6, achieving a power conversion efficiency (PCE) of more than 20%. This remarkable performance is attributed to the large twisting angle that effectively prevents the excessive aggregation of large π‐conjugated planar molecules.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"95 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901621","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":"Constructing Ionic Transport Network via Supramolecular Composite Binder in Cathode for All‐Solid‐State Lithium Batteries","authors":"Haihui Wang, Haixing Liu, Suqing Wang, Wenhan Kong, Yangxi Liu","doi":"10.1002/anie.202507579","DOIUrl":"https://doi.org/10.1002/anie.202507579","url":null,"abstract":"Binders play a pivotal role in maintaining the structural integrity and stability of electrodes. However, conventional polyvinylidene fluoride binder with low ionic conductivity could not meet the ionic transport requirements of the cathode in all‐solid‐state lithium batteries (ASSLBs). Herein, a composite binder (PPCL) derived from the cross‐linking of linear molecules and mechanically interlocked molecules with typical supramolecular channel structure is designed. The supramolecular channel structure is afforded through β‐cyclodextrin rings crosslinked polyethylene oxide chains by hydrogen bond interaction. Through the coordination of supramolecular with linear polymer, the PPCL binder provides multiple and synergistic Li+ transport channels to achieve stable Li+ transport inside the cathode. As a result, the obtained PPCL binder not only maintains exceptional adhesive strength which could achieve robust electrode structural stability but also helps to construct multiple and highly efficient Li+ transport channels. Therefore, with PPCL binder, the LiFePO4‐based ASSLBs show an excellent rate capability and long cyclic stability over 1000 cycles at 1 C. Notably, a pouch ASSLB shows excellent cycling stability over 250 cycles at 0.2 C. This work provides guidance on designing high‐loading cathodes for advanced ASSLBs.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"95 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901625","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":"On‐demand Ligate and Release Strategy based on Photoclick Reaction in Tandem with Pd‐mediated Deallylation","authors":"Boon Shing Loh, Hanqing Pang, Soh Wah Yong, Cheng Weng, Wee Han Ang","doi":"10.1002/anie.202425479","DOIUrl":"https://doi.org/10.1002/anie.202425479","url":null,"abstract":"The development of chemoselective tools that can conjugate, modify and decouple chemical groups from biomacromolecules has enabled the study of biological processes at increasing levels of fidelity. Until recently, these tools can either couple chemical entities to biomacromolecules or decouple them, but not both. A method that can perform these functions in distinct steps on demand would be highly useful. To that end, we devised a new‐to‐nature strategy by bringing together and modifying two biocompatible transformations. In this new strategy, ligation is accomplished via the photoclick reaction between an allenyl motif with 9,10‐phenanthrenequinone which installs an allyl group at the site of conjugation. This allyl group can then be selectively utilized as a handle for phenolic release via Pd‐mediated deallylation. As a proof of concept, we demonstrated its utility in the selective labelling and delabelling of model protein scaffolds and cellular matrix. This multifunctional method paves the way for controllable “ligate and release” strategy that enables on‐demand visualization of biological entities but with an in‐built release mechanism to restore their original state.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"17 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903026","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":"Unlocking One‐Step Two‐Electron Oxygen Reduction via Metalloid Boron‐Modified Zn3In2S6 for Efficient H2O2 Photosynthesis","authors":"Ji-Li Zhou, Yan-Fei Mu, Meng Qiao, Meng-Ran Zhang, Su-Xian Yuan, Min Zhang, Tong-Bu Lu","doi":"10.1002/anie.202506963","DOIUrl":"https://doi.org/10.1002/anie.202506963","url":null,"abstract":"The indirect two‐step two‐electron oxygen reduction reaction (2e− ORR) dominates photocatalytic H2O2 synthesis but suffers form sluggish kinetics, •O2−‐induced catalyst degradation, and spatiotemporal carrier‐intermediate mismatch. Herein, we pioneer a metal‐metalloid dual‐site strategy to unlock the direct one‐step 2e− ORR pathway, demonstrated through boron‐engineered Zn3In2S6 (B‐ZnInS) photocatalyst with In‐B dual‐active sites. The In‐B dual‐site configuration creates a charge‐balanced electron reservoir by charge complementation, which achieves moderate O2 adsorption via bidentate coordination and dual‐channel electron transfer, preventing excessive O−O bond activation. Simultaneously, boron doping induces lattice polarization to establish a built‐in electric field, quintupling photogenerated carrier lifetimes versus pristine ZnInS. These synergies redirect the O2 activation pathway from indirect to direct 2e− ORR process, delivering an exceptional H2O2 production rate of 3121 μmol g−1 h−1 in pure water under simulated AM 1.5G illumination (100 mW cm−2)—an 11‐fold enhancement over ZnInS. The system achieves an unprecedented apparent quantum yield of 49.8% at 365 nm for H2O2 photosynthesis among inorganic semiconducting photocatalysts, and can continuously produce medical‐grade H2O2 (3 wt%). This work provides insights for designing efficient H2O2 photocatalysts and beyond.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"112 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901617","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":"Regulating Ion Transport through Direct Coordination in Composite Gel Polymer Electrolytes towards High‐voltage and High‐loading Quasi‐solid‐state Lithium Metal Batteries","authors":"Siyang Ye, Yuji Zhang, Yiheng Huang, Yan Li, Zhaojie Li, Chuan Ou, Minghui Lin, Fei Tian, Danni Lei, Chengxin Wang","doi":"10.1002/anie.202506662","DOIUrl":"https://doi.org/10.1002/anie.202506662","url":null,"abstract":"Poly(ethylene oxide)‐based composite gel polymer electrolyte is widely used in lithium metal batteries to address dendrite growth and side reactions. However, the low oxidative decomposition potential (&lt; 4 V) of poly(ethylene oxide) limits the cyclic stability with Ni‐rich layered cathodes. What’s more, poor interface compatibility between fillers and polymer severely deteriorates lithium‐ion pathways, which cannot achieve lithium metal batteries with high‐load cathode. Herein, polyether monomers coordinate with aluminum ethoxide nanowires via in‐situ ultraviolet curing, stabilizing the lone pair electrons of ethereal oxygen atoms and suppressing oxidative degradation. This coordination also forms abundant and tight interfaces as the predominant lithium‐ion conduction pathways, contributing to ordered lithium‐ion fluxes and dendrite‐free deposition on the lithium anode. In addition, a robust solid electrolyte interphase containing aluminum‐based species enhances the interfacial stability of lithium anode. Meanwhile, the good compatibility between the electrolyte and the cathode effectively suppresses side reactions and contributes to the structural stabilization of the cycled cathode. The delicate design allows the Li||LiNi0.6Co0.2Mn0.2O2 cells to present excellent cycling stability from −20 oC to 60 oC. Specially, cells with 8.8 mg cm−2 cathode cycle stably for over 120 cycles. This molecular structure engineering will greatly promote the practical application of solid‐state lithium metal batteries.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"15 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901685","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":"Caterina G. C. Marques Netto","authors":"Caterina G. C. Marques Netto","doi":"10.1002/anie.202508876","DOIUrl":"https://doi.org/10.1002/anie.202508876","url":null,"abstract":"“<i>A major challenge in my career that I had to overcome was bias. It's something I've encountered frequently, and navigating it requires constant self-awareness, resilience, and confidence in my own worth… The research project in my group that I am most excited about is our work on bioinspired copper catalysts</i>…”","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"52 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901619","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}