Christian Ritschel, Anja Appenzeller, Radian Popescu, Carsten Donsbach, Ralf Köppe, Jonas O Wenzel, Frank Breher, Yolita M Eggeler, Wim Klopper, Claus Feldmann
{"title":"Redox Reactions with Calcium-Metal Nanoparticles.","authors":"Christian Ritschel, Anja Appenzeller, Radian Popescu, Carsten Donsbach, Ralf Köppe, Jonas O Wenzel, Frank Breher, Yolita M Eggeler, Wim Klopper, Claus Feldmann","doi":"10.1002/anie.202515995","DOIUrl":"https://doi.org/10.1002/anie.202515995","url":null,"abstract":"<p><p>Calcium is generally a highly reactive alkaline-earth metal, but as bulk metal, it exhibits only low reactivity at ambient conditions due to small surface area, low solubility, and/or passivation. The reactivity can be significantly enhanced when using small-sized calcium nanoparticles. In this regard, we describe the first synthesis of Ca(0) nanoparticles, 5.4 ± 1.2 nm in size, by TMEDA-supported reduction of CaI<sub>2</sub> with lithium naphthalenide in toluene (TMEDA: N,N,N',N'-tetramethylethylenediamine). We also show Ca(0) nanoparticles to be substantially different from so-called \"Rieke calcium\". The high reactivity can be used for redox reactions, for instance, with [Cp<sub>2</sub>MoCl<sub>2</sub>] and the sterically demanding β-diketiminate ligand H<sup>Dipp</sup>NacNac (Dipp: 2,6-iPr<sub>2</sub>C<sub>6</sub>H<sub>3</sub>) or with [(Ph<sub>3</sub>P)AuCl] as a derivative of a ligand-stabilized noble metal. The Ca(0)-nanoparticle-driven reactions result in the novel compounds [{(<sup>Dipp</sup>NacNac)(thf)Ca}<sub>2</sub>(naph)] (1) with a rare naphthalenide dianion, [{(<sup>Dipp</sup>NacNac)(thf)CaMo(Cp)H}<sub>2</sub>(fulvalene)] (2) with unusual MoH → Ca dative bonding, and [Au<sub>9</sub>(PPh<sub>3</sub>)<sub>8</sub>](naph)(tmeda)<sub>0.5</sub> (3) with a non-charged body-centered cubic Au<sub>9</sub> cluster core of zerovalent gold. Ca(0) nanoparticles and the compounds 1-3 are characterized by electron microscopy, X-ray diffraction (single crystals, powders), spectroscopy (IR, UV-Vis, NMR, EPR), and computation. Exemplarily, the formation of 1-3 points to the potential of nanosized alkaline-earth metals for chemical syntheses and the different reactivity of nanosized and bulk metals.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202515995"},"PeriodicalIF":16.9,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145369369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henrico Langeveld, Keletso Maepa, Marché Maree, Jessica L Thibaud, Nicolaas Salomane, Rosie Bridgwater, Mufuliat T Famodimu, Luiz C Godoy, Charisse Flerida A Pasaje, Nonlawat Boonyalai, Mariana Laureano de Souza, Justin Fong, Tayla Rabie, Mariëtte van der Watt, Rensu P Theart, Sonja Ghidelli-Disse, Jacquin C Niles, Marcus C S Lee, Elizabeth A Winzeler, Michael J Delves, Kelly Chibale, Kathryn J Wicht, Lauren B Coulson, Lyn-Marié Birkholtz
{"title":"Targeting Aurora Kinases as Essential Cell-Cycle Regulators to Deliver Multi-Stage Antimalarials Against Plasmodium Falciparum.","authors":"Henrico Langeveld, Keletso Maepa, Marché Maree, Jessica L Thibaud, Nicolaas Salomane, Rosie Bridgwater, Mufuliat T Famodimu, Luiz C Godoy, Charisse Flerida A Pasaje, Nonlawat Boonyalai, Mariana Laureano de Souza, Justin Fong, Tayla Rabie, Mariëtte van der Watt, Rensu P Theart, Sonja Ghidelli-Disse, Jacquin C Niles, Marcus C S Lee, Elizabeth A Winzeler, Michael J Delves, Kelly Chibale, Kathryn J Wicht, Lauren B Coulson, Lyn-Marié Birkholtz","doi":"10.1002/anie.202518493","DOIUrl":"https://doi.org/10.1002/anie.202518493","url":null,"abstract":"<p><p>Kinases play critical roles in the development and adaptation of Plasmodium falciparum and present novel opportunities for chemotherapeutic intervention. Mitotic kinases that regulate the proliferation of the parasites by controlling nuclear division, segregation, and cytokinesis. We evaluated the potential of human Aurora kinase (Aur) inhibitors to prevent P. falciparum development by targeting members of the Aurora-related kinase (Ark) family in this parasite. Several human AurB inhibitors exhibited multistage potency (< 250 nM) against all proliferative stages of parasite development, including asexual blood stages, liver schizonts, and male gametes. The most potent compounds, hesperadin, TAE684, and AT83, exhibited > 1000x selectivity towards the parasite. Importantly, we identified PfArk1 as the principal vulnerable Ark family member, with specific inhibition of PfArk1 as the primary target for hesperadin. Hesperadin's whole-cell and protein activity validates it as a unique PfArk1 tool compound. Inhibition of PfArk1 results in the parasite's inability to complete mitotic processes, presenting with unsegregated, multi-lobed nuclei caused by aberrant microtubule organization. This suggests PfArk1 is the main Aur mitotic kinase in proliferative stages of Plasmodium, characterized by bifunctional AurA and B activity. This paves the way for drug-discovery campaigns based on hesperadin targeting PfArk1.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202518493"},"PeriodicalIF":16.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Franziska Walterspiel, Begoña Ugarte-Uribe, Jonas Weidenhausen, Merrin Vincent, Kaarjel K Narayanasamy, Anna Dimitriadi, Arif Ul Maula Khan, Martin Fritsch, Christoph W Müller, Timo Zimmermann, Claire Deo
{"title":"A Photoswitchable HaloTag for Spatiotemporal Control of Fluorescence in Living Cells.","authors":"Franziska Walterspiel, Begoña Ugarte-Uribe, Jonas Weidenhausen, Merrin Vincent, Kaarjel K Narayanasamy, Anna Dimitriadi, Arif Ul Maula Khan, Martin Fritsch, Christoph W Müller, Timo Zimmermann, Claire Deo","doi":"10.1002/anie.202424955","DOIUrl":"https://doi.org/10.1002/anie.202424955","url":null,"abstract":"<p><p>Photosensitive fluorophores, whose emission can be controlled using light, are essential for advanced biological imaging, enabling precise spatiotemporal tracking of molecular features and facilitating super-resolution microscopy techniques. Although irreversibly photoactivatable fluorophores are well established, reversible reporters that can be reactivated multiple times remain scarce, and only a few have been applied in living cells using generalizable protein labeling methods. To address these limitations, we introduce chemigenetic photoswitchable fluorophores, leveraging the self-labeling HaloTag protein with fluorogenic rhodamine dye ligands. By incorporating a light-responsive protein domain into HaloTag, we engineer a tunable, photoswitchable HaloTag (psHaloTag), which can reversibly modulate the fluorescence of a bound dye-ligand via a light-induced conformational change. Our best performing psHaloTag variants show excellent performance in living cells, with large, reversible, deep-red fluorescence turn-on upon 450 nm illumination across various biomolecular targets and SMLM compatibility. Together, this work establishes the chemigenetic approach as a versatile platform for the design of photoswitchable reporters, tunable through both genetic and synthetic modifications, with promising applications for dynamic imaging.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202424955"},"PeriodicalIF":16.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Concomitant Near-Infrared Photothermy and Photoluminescence of Rod-Shaped Au<sub>52</sub>(PET)<sub>32</sub> and Au<sub>66</sub>(PET)<sub>38</sub> Synthesized Concurrently.","authors":"","doi":"10.1002/anie.202522181","DOIUrl":"https://doi.org/10.1002/anie.202522181","url":null,"abstract":"","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202522181"},"PeriodicalIF":16.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[3]CycloBODIPY: A Highly Strained Cyclic BODIPY Trimer with Effective Macrocyclic Conjugation.","authors":"Masaki Sugino, Yoshitaka Tsuchido, Rento Maeda, Ichiro Hisaki, Hideaki Takano, Hiroshi Shinokubo","doi":"10.1002/anie.202519612","DOIUrl":"https://doi.org/10.1002/anie.202519612","url":null,"abstract":"<p><p>Cyclic oligomers containing porphyrinic chromophores have attracted significant attention in broad areas of science as artificial models for photosynthetic light-harvesting antennae due to their structural and functional resemblance to natural chlorophyll arrays. Here, the synthesis of a macrocyclic [3]cycloBODIPY derivative, which consists of only boron-dipyrromethene (BODIPY) units, via an Au-mediated macrocyclization protocol is reported. While this [3]cycloBODIPY derivative exhibits a high total strain energy of 86.4 kcal mol<sup>-1</sup>, part of the intrinsic strain is effectively dispersed due to the flexible boron centers. Furthermore, this [3]cycloBODIPY derivative exhibits near-infrared (NIR) absorption reaching 1050 nm as the result of two electronic modulation factors, i.e., deformation of the BODIPY subunits and effective π-conjugation over the entire macrocycle.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202519612"},"PeriodicalIF":16.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gizem Gokce-Alpkilic, Buwei Huang, Andi Liu, Lieselotte S M Kreuk, Yaxi Wang, Victor Adebomi, Yensi Flores Bueso, Asim K Bera, Alex Kang, Stacey R Gerben, Stephen Rettie, Dionne K Vafeados, Nicole Roullier, Inna Goreshnik, Xinting Li, David Baker, Joshua J Woodward, Joseph D Mougous, Gaurav Bhardwaj
{"title":"De Novo Design of High-Affinity Miniprotein Binders Targeting Francisella Tularensis Virulence Factor.","authors":"Gizem Gokce-Alpkilic, Buwei Huang, Andi Liu, Lieselotte S M Kreuk, Yaxi Wang, Victor Adebomi, Yensi Flores Bueso, Asim K Bera, Alex Kang, Stacey R Gerben, Stephen Rettie, Dionne K Vafeados, Nicole Roullier, Inna Goreshnik, Xinting Li, David Baker, Joshua J Woodward, Joseph D Mougous, Gaurav Bhardwaj","doi":"10.1002/anie.202516058","DOIUrl":"https://doi.org/10.1002/anie.202516058","url":null,"abstract":"<p><p>Francisella tularensis poses considerable public health risk due to its high infectivity and potential for bioterrorism. Francisella-like lipoprotein (Flpp3), a key virulence factor unique to Francisella, plays critical roles in infection and immune evasion, making it a promising target for therapeutic development. However, the lack of well-defined binding pockets and structural information on native interactions has hindered structure-guided ligand discovery against Flpp3. Here, we used a combination of physics-based and deep-learning methods to design high-affinity miniprotein binders targeting two distinct sites on Flpp3. We identified four binders for site I with binding affinities ranging between 24-110 nM. For the second site, an initial binder showed a dissociation constant (K<sub>D</sub>) of 81 nM, and subsequent site saturation mutagenesis yielded variants with sub-nanomolar affinities. Circular dichroism confirmed the topology of designed miniproteins. The X-ray crystal structure of Flpp3 in complex with a site I binder is nearly identical to the design model (Cα root-mean-square deviation (RMSD): 0.9 Å). These designed miniproteins provide research tools to explore the roles of Flpp3 in tularemia and should enable the development of new therapeutic candidates.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202516058"},"PeriodicalIF":16.9,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Photochemical Di-π-Methane Rearrangement Reactions.","authors":"Qi-Xin Dong, Yi-Hong Ke, Ying Zhang, Huan-Ming Huang","doi":"10.1002/anie.202519769","DOIUrl":"https://doi.org/10.1002/anie.202519769","url":null,"abstract":"<p><p>Photochemical di-π-methane (DPM) rearrangement, a classic transformation pioneered by Zimmerman, elegantly converts 1,4-dienes and related systems into complex, strain-rich vinylcyclopropane architectures. For decades, its utility in organic synthesis was constrained by its reliance on direct UV irradiation, which limited functional group tolerance and practical application. However, the recent integration of this elegant photochemical rearrangement with the principles of visible-light-mediated triplet energy transfer catalysis has sparked a dramatic renaissance. This review chronicles the journey of the DPM rearrangement from its foundational mechanistic principles to its modern catalytic incarnation. We detail the expansion of the reaction family-encompassing oxa- (ODPM) and aza-di-π-methane (ADPM) variants-and highlight its evolving applications in the total synthesis of natural products and beyond. Finally, we offer a perspective on future opportunities, underscoring how this venerable reaction continues to enable synthetic innovation and discovery in the 21<sup>st</sup> century.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202519769"},"PeriodicalIF":16.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sotirios Pavlidis, Christian Teutloff, Ana Guilherme Buzanich, Konstantin B Krause, Franziska Emmerling, Robert Bittl, Josh Abbenseth
{"title":"A Crystalline Bismuth(II) Radical Anion: Synthesis, Characterization, and Reactivity.","authors":"Sotirios Pavlidis, Christian Teutloff, Ana Guilherme Buzanich, Konstantin B Krause, Franziska Emmerling, Robert Bittl, Josh Abbenseth","doi":"10.1002/anie.202515545","DOIUrl":"https://doi.org/10.1002/anie.202515545","url":null,"abstract":"<p><p>We report the synthesis of a planarized tris-amidobismuthane supported by a rigid, bulky NNN pincer ligand, which enforces a T-shaped geometry at the bismuth center. The Bi(NNN) complex features a low-lying LUMO with distinct Bi(6p) orbital character as shown by DFT calculations. Cyclic voltammetry reveals a fully reversible one-electron reduction at E<sub>1/2</sub> = -1.85 V versus Fc<sup>0/+</sup> in THF. Chemical reduction with KC<sub>8</sub> in the presence of 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (222-crypt) enables the isolation of an unprecedented Bi(II) radical anion in high isolated yields. Multi-frequency EPR, X-ray absorption spectroscopy and SQUID magnetometry complemented by theoretical calculations confirm localization of the unpaired electron on the bismuth center. Preliminary reactivity studies display radical reactivity as shown by single-electron transfer chemistry and radical coupling reactions.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202515545"},"PeriodicalIF":16.9,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacob A Vance, Wei-An Chen, Palina Nepachalovich, Caroline Knittel, Maria Fedorova, Neal K Devaraj
{"title":"Targeted Detection of Phospholipid Aldehydes in Living Cells by Oxime Ligation.","authors":"Jacob A Vance, Wei-An Chen, Palina Nepachalovich, Caroline Knittel, Maria Fedorova, Neal K Devaraj","doi":"10.1002/anie.202512578","DOIUrl":"https://doi.org/10.1002/anie.202512578","url":null,"abstract":"<p><p>Oxidatively damaged lipids play critical roles in numerous human pathologies, yet methods to directly identify these species within living cells remain limited due to their transient and low-abundance nature. Among lipid oxidation products, aldehyde-containing lipids are significant due to their heightened reactivity and strong links to disease pathology. Here, we introduce OxiLox (oxime ligation to oxidized lipids), a method that leverages fluorescent hydroxylamine-based probes to enable direct, chemoselective tagging of aldehyde-containing lipids within living cells via rapid oxime ligation. Using confocal microscopy, we observe the subcellular localization of these oxidized lipids, highlighting prominent accumulation within perinuclear membranes, particularly under oxidative stress conditions induced by the ferroptosis activator RSL3. Coupled with high-resolution mass spectrometry, our method identifies aldehyde lipid species, notably revealing the abundance of oxidized plasmenyl phosphatidylethanolamines in ferroptotic cells. We demonstrate that cellular labeling by hydroxylamine probes can be modulated by altering the expression of antioxidant enzymes such as aldose reductase (AKR1B1), underscoring the relationship between enzymatic antioxidant defenses and lipid aldehyde metabolism. Our work establishes OxiLox as a robust approach for direct, sensitive, and chemically precise detection of lipid aldehydes in live cells, offering new insights into the role of lipid oxidation in health and disease.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202512578"},"PeriodicalIF":16.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Youwei Ma.","authors":"Youwei Ma","doi":"10.1002/anie.202520832","DOIUrl":"https://doi.org/10.1002/anie.202520832","url":null,"abstract":"<p><p>\"My favorite structure is β-dicarbonyl because of its versatile reactivity… If I could have dinner with a well-known historic figure, I would invite Hermann Staudinger and I would ask him how he views the progress of polymer science today…\" Find out more about Youwei Ma in his Introducing… Profile.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202520832"},"PeriodicalIF":16.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}