4-Amino-2,4-pentadienoate-containing cyclolipodepsipeptides (APD-CLDs) represent a structurally distinctive family of natural products known for their selective activity against hypoxic cancer cells. To explore the structural diversity of APD-CLDs, we have identified and prioritized cryptic APD-CLD biosynthetic gene clusters (BGCs) for compound discovery. Using a combination of genetic and chemical methods, we successfully activated three dormant BGCs, leading to the discovery of 12 new APD-CLDs. These newly discovered metabolites significantly expanded the diversity of the APD-CLD family, with chloromalamides and arabimalamides representing the first halogenated and glycosylated members, respectively. Unexpectedly, chloromalamides and arabimalamides exhibited potent antiplasmodial activity, with IC50 values in the 25-161 nM range against drug-sensitive and multidrug-resistant Plasmodium falciparum strains. Phenotypic studies revealed arabimalamide B halted parasite development during the asexual blood stage life cycle, resulting in enlarged digestive vacuoles, dispersed hemozoin, and ultimately reduced reinvasion efficiency. These phenotypes are reminiscent of the effect of chloroquine and other 4-aminoquinoline drugs, suggesting that arabimalamides may disrupt the parasite's heme detoxification mechanism. Biosynthetic studies identified key scaffold-forming and modifying enzymes, including a rare membrane glycosyltransferase in arabimalamide biosynthesis. Together, these findings unveil APD-CLDs as new antimalarial lead scaffolds and set the stage for structural diversification and optimization.
{"title":"Genome-Guided Discovery of Antimalarial 4-Amino-2,4-Pentadienoate-Containing Cyclolipodepsipeptides.","authors":"Hartono Candra,Xue-Jiao Wang,Ka Diam Go,Li Feng,Miaomiao Cai,Guang-Lei Ma,Clarissa Widyantoro,Lik Tong Tan,Zbynek Bozdech,Zhe Wang,Zhao-Xun Liang","doi":"10.1002/anie.202523372","DOIUrl":"https://doi.org/10.1002/anie.202523372","url":null,"abstract":"4-Amino-2,4-pentadienoate-containing cyclolipodepsipeptides (APD-CLDs) represent a structurally distinctive family of natural products known for their selective activity against hypoxic cancer cells. To explore the structural diversity of APD-CLDs, we have identified and prioritized cryptic APD-CLD biosynthetic gene clusters (BGCs) for compound discovery. Using a combination of genetic and chemical methods, we successfully activated three dormant BGCs, leading to the discovery of 12 new APD-CLDs. These newly discovered metabolites significantly expanded the diversity of the APD-CLD family, with chloromalamides and arabimalamides representing the first halogenated and glycosylated members, respectively. Unexpectedly, chloromalamides and arabimalamides exhibited potent antiplasmodial activity, with IC50 values in the 25-161 nM range against drug-sensitive and multidrug-resistant Plasmodium falciparum strains. Phenotypic studies revealed arabimalamide B halted parasite development during the asexual blood stage life cycle, resulting in enlarged digestive vacuoles, dispersed hemozoin, and ultimately reduced reinvasion efficiency. These phenotypes are reminiscent of the effect of chloroquine and other 4-aminoquinoline drugs, suggesting that arabimalamides may disrupt the parasite's heme detoxification mechanism. Biosynthetic studies identified key scaffold-forming and modifying enzymes, including a rare membrane glycosyltransferase in arabimalamide biosynthesis. Together, these findings unveil APD-CLDs as new antimalarial lead scaffolds and set the stage for structural diversification and optimization.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"16 1","pages":"e23372"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471509","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}
Guoliang Wei,Guangyuan He,Jinying Yu,Kuizhi Chen,Xuebing Li,Yu Gu,Donghai Mei,Hui Shi
Modern catalytic approaches to manipulating reactivities predominantly rely on (post-)synthetic methods that engineer active sites and their local environments from a materials perspective, while the dynamic creation and disruption of reactive and spectator species through co-adsorbate interactions is much less explored and understood. Herein, C3─C6 aliphatic alkanones have been identified as potent promotors for Brønsted acid-catalyzed alkanol dehydration within the subnanometric zeolite pores, with the MFI topology being the most efficacious (up to two orders of magnitude rate enhancement and > 99.8% olefin) and featuring a remarkable stability (> 140 h on stream) at both kinetically limited and practically relevant conversions. Rigorous kinetic descriptions are combined with density functional theory methods to assess the structures, stabilities and reactivities of all plausible intermediates derived from the reactant and cofeed during 2-propanol (IPA) dehydration in MFI pores. Stoichiometric clustering of alkanones with IPA-derived monomers and dimers, driven by strong H-bonds and stabilized by pore confinement, induces the formation of protonated bi- and termolecular species with distinct reactivities for intra- and intermolecular dehydration, which depends on the alkanone identity. These mechanistic underpinnings reward us with an ability to predict reactivity and selectivity trends and rationally design optimal solvent systems or cofeeding schemes for alkanol dehydration.
{"title":"Stabilization of Alkanol-Alkanone Heteroclusters in Medium-Pore Zeolites Drives Orders-of-Magnitude Rate Enhancements in Proton-Catalyzed Dehydration Reactions.","authors":"Guoliang Wei,Guangyuan He,Jinying Yu,Kuizhi Chen,Xuebing Li,Yu Gu,Donghai Mei,Hui Shi","doi":"10.1002/anie.202519476","DOIUrl":"https://doi.org/10.1002/anie.202519476","url":null,"abstract":"Modern catalytic approaches to manipulating reactivities predominantly rely on (post-)synthetic methods that engineer active sites and their local environments from a materials perspective, while the dynamic creation and disruption of reactive and spectator species through co-adsorbate interactions is much less explored and understood. Herein, C3─C6 aliphatic alkanones have been identified as potent promotors for Brønsted acid-catalyzed alkanol dehydration within the subnanometric zeolite pores, with the MFI topology being the most efficacious (up to two orders of magnitude rate enhancement and > 99.8% olefin) and featuring a remarkable stability (> 140 h on stream) at both kinetically limited and practically relevant conversions. Rigorous kinetic descriptions are combined with density functional theory methods to assess the structures, stabilities and reactivities of all plausible intermediates derived from the reactant and cofeed during 2-propanol (IPA) dehydration in MFI pores. Stoichiometric clustering of alkanones with IPA-derived monomers and dimers, driven by strong H-bonds and stabilized by pore confinement, induces the formation of protonated bi- and termolecular species with distinct reactivities for intra- and intermolecular dehydration, which depends on the alkanone identity. These mechanistic underpinnings reward us with an ability to predict reactivity and selectivity trends and rationally design optimal solvent systems or cofeeding schemes for alkanol dehydration.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"8 1","pages":"e19476"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471579","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}
Aqueous microdroplets have received attention due to their peculiar physicochemical properties, such as their ability to drive unfavorable chemical reactions orders of magnitude more quickly than in the bulk phase. However, very few techniques can probe microdroplets, one-at-a-time. Even fewer techniques can also provide real time information on the physical properties of the microdroplet reactor at the nanoscale. Such properties are highly important for rigorous mechanistic investigations. Here, we demonstrate a simple electrochemical method to quantify the nanometer contact radius that forms between a colliding droplet and an electrified surface, as a function of time. We address the limitations in the previous model used for sizing the nanometric contact area and offer a new quantitative framework. These new analyses give access to nanoscale wetting dynamics of individual microdroplets on an electrified micro-interface. We demonstrate control over the microdroplet wetting dynamics using electrostatics. Finally, we use this platform to drive reactions within individual adsorbed microdroplets. We track the oxygen reduction reaction in real time at the well characterized microdroplet|microelectrode contact, extracting the actively partition-controlled oxygen concentration in single microdroplets. These results have high sensitivity, allowing us to decipher both physical properties of droplets far below the diffraction limit of light and measure reactions at nanoscale, multiphase surfaces.
{"title":"Measuring the Dynamic Nanometric Contact Radius of a Single Microdroplet on an Electrified Microinterface.","authors":"Kathryn J Vannoy,Jeffrey Dick,Marc Koper","doi":"10.1002/anie.1113423","DOIUrl":"https://doi.org/10.1002/anie.1113423","url":null,"abstract":"Aqueous microdroplets have received attention due to their peculiar physicochemical properties, such as their ability to drive unfavorable chemical reactions orders of magnitude more quickly than in the bulk phase. However, very few techniques can probe microdroplets, one-at-a-time. Even fewer techniques can also provide real time information on the physical properties of the microdroplet reactor at the nanoscale. Such properties are highly important for rigorous mechanistic investigations. Here, we demonstrate a simple electrochemical method to quantify the nanometer contact radius that forms between a colliding droplet and an electrified surface, as a function of time. We address the limitations in the previous model used for sizing the nanometric contact area and offer a new quantitative framework. These new analyses give access to nanoscale wetting dynamics of individual microdroplets on an electrified micro-interface. We demonstrate control over the microdroplet wetting dynamics using electrostatics. Finally, we use this platform to drive reactions within individual adsorbed microdroplets. We track the oxygen reduction reaction in real time at the well characterized microdroplet|microelectrode contact, extracting the actively partition-controlled oxygen concentration in single microdroplets. These results have high sensitivity, allowing us to decipher both physical properties of droplets far below the diffraction limit of light and measure reactions at nanoscale, multiphase surfaces.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"4 1","pages":"e1113423"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471502","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}
For antiaromatic polycyclic hydrocarbons (PHs), heterocycle-fusion is an efficient approach to alter their electronic structures and physical properties. Herein, we disclose pristine boracycle-annulation of antiaromatic π-systems. Two organoboron PHs designed by fusion of 1-boraphenalenes onto one s-indacene or dicyclopenta[b,g]naphthalene core were synthesized. As studied, this boracycle-annulation remarkably stabilizes the antiaromaticity of s-indacene owing to the B atom with small electronegativity, and moderately enhances diradical character of dicyclopenta[b,g]naphthalene by inducing cross conjugation between the B atoms and radical centers and promoting spin delocalization. These electronic effects are in stark contrast to those of other N-/O-/S-heterocycles, thus demonstrating the unique contributions of the B atoms. Furthermore, they show a few intriguing optoelectronic properties, such as near-infrared absorptions, short excited-state lifetimes and four-step redox activity. In-depth investigations demonstrate that the amphoteric antiaromatic core together with the electron-accepting B-containing rings make significant contributions to their characteristic properties. Thus, these findings may serve as an important basis for the design of functional heterocyclic PHs, especially antiaromatic and diradical materials.
{"title":"Boracycle-Annulation Stabilizes Antiaromaticity and Enhances Diradical Character in s-Indacene/Dicyclopenta[b,g]Naphthalene-Cored Organoboron Polycyclic Hydrocarbons.","authors":"Jingyuan Yang,Liuzhong Yuan,Yujia Liu,Xinyu Tian,Shihou Sheng,Zeyi Li,Chuandong Dou","doi":"10.1002/anie.1718544","DOIUrl":"https://doi.org/10.1002/anie.1718544","url":null,"abstract":"For antiaromatic polycyclic hydrocarbons (PHs), heterocycle-fusion is an efficient approach to alter their electronic structures and physical properties. Herein, we disclose pristine boracycle-annulation of antiaromatic π-systems. Two organoboron PHs designed by fusion of 1-boraphenalenes onto one s-indacene or dicyclopenta[b,g]naphthalene core were synthesized. As studied, this boracycle-annulation remarkably stabilizes the antiaromaticity of s-indacene owing to the B atom with small electronegativity, and moderately enhances diradical character of dicyclopenta[b,g]naphthalene by inducing cross conjugation between the B atoms and radical centers and promoting spin delocalization. These electronic effects are in stark contrast to those of other N-/O-/S-heterocycles, thus demonstrating the unique contributions of the B atoms. Furthermore, they show a few intriguing optoelectronic properties, such as near-infrared absorptions, short excited-state lifetimes and four-step redox activity. In-depth investigations demonstrate that the amphoteric antiaromatic core together with the electron-accepting B-containing rings make significant contributions to their characteristic properties. Thus, these findings may serve as an important basis for the design of functional heterocyclic PHs, especially antiaromatic and diradical materials.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"5 1","pages":"e1718544"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471790","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}
Yan Wu,Xing Gao,Rui Yu,Chengyang Zhu,Dongyang Yu,Zaizhu Lou,Zhujie Li,Gang Wang
Targeted transport of electrons is essential to enable the photoreduction process efficiently, which remains a significant challenge in current research. Constructing "molecule-junction" between photocatalyst and metal active sites is expected to achieve the precise directional electron transfer. 2-Mercaptonicotinic acid (H2L), with both sulfhydryl groups (─SH) and a conjugated pyridine ring, was introduced as the intermediary to build "molecule-junction" connecting Ni-doped BiOCl (Ni/BOC) and Au NPs (denoted as Ni/BOC-H2L-Au). XPS and XAFS results confirm the existence of Bi─S and Au─S bonds, which verify that the "molecule-junction" of Bi─H2L─Au have been successfully constructed in Ni/BOC. Due to the unique structure of Ni/BOC-H2L-Au, it showed excellent performance in CO2 photoreduction. In the absence of sacrificial agents, the ethane (C2H6) yield (155.4 µmol g-1 h-1) and selectivity (85.8%) exceeded most of the reported photocatalysts. The combined theoretical and experimental analysis demonstrates that the "molecule-junction" establishes a directional electron transfer pathway (Ni/BOC→H2L→Au NPs), which significantly enhances charge separation efficiency and promotes targeted electron accumulation at Au NPs active sites, thereby boosting C2H6 production via CO2 photoreduction. This work proposes a viable strategy for designing efficient photocatalysts for high-value C2+ product synthesis.
{"title":"Engineered \"Molecule-Junction\" to Transport Photo-Generated Electrons for CO2 Reduction to Ethane.","authors":"Yan Wu,Xing Gao,Rui Yu,Chengyang Zhu,Dongyang Yu,Zaizhu Lou,Zhujie Li,Gang Wang","doi":"10.1002/anie.2699441","DOIUrl":"https://doi.org/10.1002/anie.2699441","url":null,"abstract":"Targeted transport of electrons is essential to enable the photoreduction process efficiently, which remains a significant challenge in current research. Constructing \"molecule-junction\" between photocatalyst and metal active sites is expected to achieve the precise directional electron transfer. 2-Mercaptonicotinic acid (H2L), with both sulfhydryl groups (─SH) and a conjugated pyridine ring, was introduced as the intermediary to build \"molecule-junction\" connecting Ni-doped BiOCl (Ni/BOC) and Au NPs (denoted as Ni/BOC-H2L-Au). XPS and XAFS results confirm the existence of Bi─S and Au─S bonds, which verify that the \"molecule-junction\" of Bi─H2L─Au have been successfully constructed in Ni/BOC. Due to the unique structure of Ni/BOC-H2L-Au, it showed excellent performance in CO2 photoreduction. In the absence of sacrificial agents, the ethane (C2H6) yield (155.4 µmol g-1 h-1) and selectivity (85.8%) exceeded most of the reported photocatalysts. The combined theoretical and experimental analysis demonstrates that the \"molecule-junction\" establishes a directional electron transfer pathway (Ni/BOC→H2L→Au NPs), which significantly enhances charge separation efficiency and promotes targeted electron accumulation at Au NPs active sites, thereby boosting C2H6 production via CO2 photoreduction. This work proposes a viable strategy for designing efficient photocatalysts for high-value C2+ product synthesis.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"17 1","pages":"e2699441"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471795","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}
The key challenges in direct seawater electrolysis for hydrogen evolution reaction (HER) are the substantially high energy demands for water dissociation and preventing catalyst surface precipitation. By grafting formate groups onto the NiFe2O4 spinel surface (NiFe2O4─HCOO─), the rigid hydrogen-bond network at the outer Helmholtz plane (OHP) are disrupted, which facilitates direct interaction with free water molecules and enhances water dissociation for HER. Especially, hydrogen-bond network disruption reduces gas-liquid interfacial tension, enabling self-cleaning by releasing dense bubbles to remove Ca2+/Mg2+ precipitates, along with enhanced bubble separation. This dual function preserves the active sites of NiFe2O4─HCOO─ for sustained seawater electrolysis. Benefiting from above, the synthesized NiFe2O4─HCOO─ delivers -1.0 A cm-2 at just 435 mV in alkaline seawater while maintaining exceptional stability over 1000 h and can be deployed in anion exchange membrane (AEM) electrolyzers with the technical and economic analysis (TEA) indicating the low cost of hydrogen production. Furthermore, this study confirms the technical feasibility of the simultaneous electrosynthesis of high-value magnesium hydroxide and hydrogen from natural seawater.
海水直接电解析氢反应（HER）的关键挑战是水解离和防止催化剂表面沉淀的高能量需求。通过在NiFe2O4尖晶石表面（NiFe2O4─HCOO─）接枝甲酸基团，破坏了NiFe2O4外层亥姆霍兹平面（OHP）上的刚性氢键网络，促进了与自由水分子的直接相互作用，增强了HER的水解离。特别是，氢键网络的破坏降低了气液界面张力，通过释放密集的气泡来去除Ca2+/Mg2+沉淀，从而实现自清洁，同时增强了气泡分离。这种双重功能保留了NiFe2O4─HCOO─的活性位点，用于持续的海水电解。得益于以上，合成的NiFe2O4─HCOO─在碱性海水中以435 mV的速度提供-1.0 A cm-2，同时在1000小时内保持出色的稳定性，并且可以部署在阴离子交换膜（AEM）电解槽中，技术和经济分析（TEA）表明制氢成本低。进一步证实了从天然海水中同时电合成高值氢氧化镁和氢的技术可行性。
{"title":"Formate-Anion-Induced Water Network Reshaping Enables Concurrent Hydrogen and Magnesium Hydroxide Production From Seawater.","authors":"Lili Guo,Fahao Sun,Fuwei Zheng,Jingqi Chi,Hailing Guo,Zhenyu Xiao,Jianping Lai,Xiaobin Liu,Zexing Wu,Lei Wang","doi":"10.1002/anie.6937994","DOIUrl":"https://doi.org/10.1002/anie.6937994","url":null,"abstract":"The key challenges in direct seawater electrolysis for hydrogen evolution reaction (HER) are the substantially high energy demands for water dissociation and preventing catalyst surface precipitation. By grafting formate groups onto the NiFe2O4 spinel surface (NiFe2O4─HCOO─), the rigid hydrogen-bond network at the outer Helmholtz plane (OHP) are disrupted, which facilitates direct interaction with free water molecules and enhances water dissociation for HER. Especially, hydrogen-bond network disruption reduces gas-liquid interfacial tension, enabling self-cleaning by releasing dense bubbles to remove Ca2+/Mg2+ precipitates, along with enhanced bubble separation. This dual function preserves the active sites of NiFe2O4─HCOO─ for sustained seawater electrolysis. Benefiting from above, the synthesized NiFe2O4─HCOO─ delivers -1.0 A cm-2 at just 435 mV in alkaline seawater while maintaining exceptional stability over 1000 h and can be deployed in anion exchange membrane (AEM) electrolyzers with the technical and economic analysis (TEA) indicating the low cost of hydrogen production. Furthermore, this study confirms the technical feasibility of the simultaneous electrosynthesis of high-value magnesium hydroxide and hydrogen from natural seawater.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"6 1","pages":"e6937994"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471572","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}
Development of homochiral hydrogen-bonded organic framework (HOF) film for highly circularly polarized luminescent (CPL) remains a significant challenge. In this study, we aim to construct HOF materials that integrate strong CPL with high chiral ordered structure through rational molecular design and supramolecular self-assembly. We designed a homochiral HOF from enantiomeric 1,1'-binaphthyl-2,2'-dihydroxy-5,5'-dicarboxylic acid (H2BDA), termed CAS-10, which crystallize in the C2221 space group, and realized its self-organization into a highly oriented film through with in situ growth strategy. Our findings reveal that the oriented HOF film displays, strong chirality and intense blue luminescence, obvious CPL performance. By strategically incorporating linear birefringence effects, the glum values reach an exceptional value of ±0.5 at 460 nm, representing a 167 times enhancement over the precursor disordered chiral molecule. This work not only presents an effective supramolecular assembly strategy for dramatically amplifying CPL performance through hydrogen-bonded networks, but also pioneers the introduction of birefringence into chiral crystalline film materials. Furthermore, these advances establish a new material platform and design principle for developing cost-effective, high-performance CPL devices with practical applicability.
{"title":"Homochiral Birefringence Hydrogen-Bonded Organic Framework Films for Highly Circularly Polarized Luminescence.","authors":"Jun-Hao Ding,Lin-Zhi Huang,Li-Mei Chang,Zhi-Gang Gu,Jian Zhang","doi":"10.1002/anie.4678241","DOIUrl":"https://doi.org/10.1002/anie.4678241","url":null,"abstract":"Development of homochiral hydrogen-bonded organic framework (HOF) film for highly circularly polarized luminescent (CPL) remains a significant challenge. In this study, we aim to construct HOF materials that integrate strong CPL with high chiral ordered structure through rational molecular design and supramolecular self-assembly. We designed a homochiral HOF from enantiomeric 1,1'-binaphthyl-2,2'-dihydroxy-5,5'-dicarboxylic acid (H2BDA), termed CAS-10, which crystallize in the C2221 space group, and realized its self-organization into a highly oriented film through with in situ growth strategy. Our findings reveal that the oriented HOF film displays, strong chirality and intense blue luminescence, obvious CPL performance. By strategically incorporating linear birefringence effects, the glum values reach an exceptional value of ±0.5 at 460 nm, representing a 167 times enhancement over the precursor disordered chiral molecule. This work not only presents an effective supramolecular assembly strategy for dramatically amplifying CPL performance through hydrogen-bonded networks, but also pioneers the introduction of birefringence into chiral crystalline film materials. Furthermore, these advances establish a new material platform and design principle for developing cost-effective, high-performance CPL devices with practical applicability.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"37 1","pages":"e4678241"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471729","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}
The field of photopharmacology develops light-responsive drugs that can modulate protein activity, enabling precise and dynamic investigations of their roles in health and disease. Adrenergic receptors are prominent targets for this approach because they are prototypical G protein-coupled receptors with high clinical relevance in bronchial and cardiovascular diseases. Here, we employed the azobenzene-based compound photoazolol-1 in combination with time-resolved serial crystallography at X-ray free-electron lasers to resolve the molecular mechanisms by which photoswitchable β-blockers modulate activity of the β2-adrenoceptor (β2AR). Time-resolved structures of the receptor bound to trans-photoazolol-1 (pre-photoconversion), a strained intermediate in the nanosecond range, and the fully photoisomerized cis-photoazolol-1 reveal how isomerization of the azobenzene moiety induces distinct conformational changes within the orthosteric ligand binding pocket. Within seconds, light-excited photoazolol-1 adopts a new binding pose, altering interactions with extracellular loop 2 and shifting the positions of transmembrane helices 5, 6, and 7. Functional assays of β2AR in cellular membranes show that photoazolol-1 acts as an efficacy photoswitch, changing from an inverse agonist to a neutral antagonist upon isomerization without leaving the binding pocket. In combination, these findings suggest a molecular mechanism for activity modulation via efficacy photoswitches and provide a framework for designing ligands that exploit light-driven transitions within the binding pocket to achieve spatiotemporal control of receptor function.
{"title":"Structural Mechanism of an Efficacy Photoswitch Targeting the β2-adrenergic Receptor.","authors":"Robin Stipp,Quentin Bertrand,Matilde Trabuco,Anna Duran-Corbera,Maria Tindara Ignazzitto,Hannah Glover,Fabienne Stierli,Juanlo Catena,Melissa Carrillo,Sina Hartmann,Hans-Peter Seidel,Matthias Mulder,Thomas Mason,Yasushi Kondo,Maximillian Wranik,Martin Appleby,Christoph Sager,Raymond Sierra,Gregory Gate,Pamela Schleissner,Xinxin Cheng,Tobias Weinert,Robert Cheng,Sandra Mous,John H Beale,Michal Kepa,Amadeu Llebaria,Michael Hennig,Xavier Rovira,Joerg Standfuss","doi":"10.1002/anie.202517995","DOIUrl":"https://doi.org/10.1002/anie.202517995","url":null,"abstract":"The field of photopharmacology develops light-responsive drugs that can modulate protein activity, enabling precise and dynamic investigations of their roles in health and disease. Adrenergic receptors are prominent targets for this approach because they are prototypical G protein-coupled receptors with high clinical relevance in bronchial and cardiovascular diseases. Here, we employed the azobenzene-based compound photoazolol-1 in combination with time-resolved serial crystallography at X-ray free-electron lasers to resolve the molecular mechanisms by which photoswitchable β-blockers modulate activity of the β2-adrenoceptor (β2AR). Time-resolved structures of the receptor bound to trans-photoazolol-1 (pre-photoconversion), a strained intermediate in the nanosecond range, and the fully photoisomerized cis-photoazolol-1 reveal how isomerization of the azobenzene moiety induces distinct conformational changes within the orthosteric ligand binding pocket. Within seconds, light-excited photoazolol-1 adopts a new binding pose, altering interactions with extracellular loop 2 and shifting the positions of transmembrane helices 5, 6, and 7. Functional assays of β2AR in cellular membranes show that photoazolol-1 acts as an efficacy photoswitch, changing from an inverse agonist to a neutral antagonist upon isomerization without leaving the binding pocket. In combination, these findings suggest a molecular mechanism for activity modulation via efficacy photoswitches and provide a framework for designing ligands that exploit light-driven transitions within the binding pocket to achieve spatiotemporal control of receptor function.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"97 1","pages":"e17995"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471800","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}
Ernesto A Hernández-Morales,Dayra Barreto-Hernández,Dazaet Galicia-Badillo,Rubén A Toscano,M Elena García-Aguilera,Braulio Rodríguez-Molina
Harnessing mechanical motion in molecular crystals is a critical goal for developing novel energy conversion materials. Among known strategies, the ejection of guest molecules from the lattice via the jumping-mate approach offers a direct means of propulsion. Here, we present isostructural cocrystals of indolo[3,2-a]carbazole (ICZ) and (E)-1,2-di(pyridin-4-yl)ethene (BPE) that incorporate solvents such as acetone, ethyl acetate, or tetrahydrofuran. X-ray diffraction and solid-state nuclear magnetic resonance (NMR) studies confirmed the presence of solvents or solvent mixtures. Upon heating, these channel-type cocrystals exhibit a thermosalient effect, with temperature regulation achieved by releasing pure or solvent mixtures. Differential scanning calorimetry and thermogravimetry (DSC-TGA) analyses revealed that the transition temperatures changed progressively, demonstrating controllable thermal actuation through the release of occluded solvents. This work demonstrates a simple yet powerful way to regulate mechanical responses in molecular crystals, thereby advancing the design of responsive energy conversion materials.
{"title":"Crystals as Rockets: Modulation of the Salient Temperature in Cocrystals by Solvent Mixture Composition.","authors":"Ernesto A Hernández-Morales,Dayra Barreto-Hernández,Dazaet Galicia-Badillo,Rubén A Toscano,M Elena García-Aguilera,Braulio Rodríguez-Molina","doi":"10.1002/anie.202526010","DOIUrl":"https://doi.org/10.1002/anie.202526010","url":null,"abstract":"Harnessing mechanical motion in molecular crystals is a critical goal for developing novel energy conversion materials. Among known strategies, the ejection of guest molecules from the lattice via the jumping-mate approach offers a direct means of propulsion. Here, we present isostructural cocrystals of indolo[3,2-a]carbazole (ICZ) and (E)-1,2-di(pyridin-4-yl)ethene (BPE) that incorporate solvents such as acetone, ethyl acetate, or tetrahydrofuran. X-ray diffraction and solid-state nuclear magnetic resonance (NMR) studies confirmed the presence of solvents or solvent mixtures. Upon heating, these channel-type cocrystals exhibit a thermosalient effect, with temperature regulation achieved by releasing pure or solvent mixtures. Differential scanning calorimetry and thermogravimetry (DSC-TGA) analyses revealed that the transition temperatures changed progressively, demonstrating controllable thermal actuation through the release of occluded solvents. This work demonstrates a simple yet powerful way to regulate mechanical responses in molecular crystals, thereby advancing the design of responsive energy conversion materials.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"77 1","pages":"e26010"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471507","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}
Swapnil Ghule,Sayan Sarkar,Maria Eugenia Pérez-Ojeda Rodriguez,Mark Spector,Frank Hampel,Evgeny A Kataev
The design of supramolecular receptors for amino acids presents a fundamentally challenging yet highly promising avenue of research. Phenylalanine attracts special attention because of its multifaceted role in living organisms. Although many synthetic hosts have been explored for recognition of phenylalanine (Phe), besides cucurbiturils, there are no receptors that show selectivity for Phe over other aromatic amino acids and related aromatic neurotransmitters in water. Toward addressing this challenge, we explored pi-conjugated water-soluble macrocycles with hydrophobic pockets. A new family of o-terphenyl-based macrocycles, TP[n] (n = 2-8) was synthesized using the Yamamoto reaction. Macrocycles up to the octamer, TP[2]-TP[8], were isolated and fully characterized. X-ray studies reveal that these macrocycles can form folded conformations stabilized by stacking interactions. TP[3] was identified as the most selective host for Phe with an affinity of 7 x 103 M-1 in water. The hosts, composed of 2-5 subunits were found to effectively inhibit protein aggregation according to the fluorescence assay using thioflavin T. The discovery of the new family of macrocycles paves the way for designing hosts with diverse architectures, precisely tailored geometries, and optimized binding properties capable of targeting not only individual amino acids but also entire protein surfaces.
{"title":"o-Terphenyl-Based Family of Conjugated Macrocycles: Selective Recognition of Phenylalanine in Water and Interaction With Insulin.","authors":"Swapnil Ghule,Sayan Sarkar,Maria Eugenia Pérez-Ojeda Rodriguez,Mark Spector,Frank Hampel,Evgeny A Kataev","doi":"10.1002/anie.202525972","DOIUrl":"https://doi.org/10.1002/anie.202525972","url":null,"abstract":"The design of supramolecular receptors for amino acids presents a fundamentally challenging yet highly promising avenue of research. Phenylalanine attracts special attention because of its multifaceted role in living organisms. Although many synthetic hosts have been explored for recognition of phenylalanine (Phe), besides cucurbiturils, there are no receptors that show selectivity for Phe over other aromatic amino acids and related aromatic neurotransmitters in water. Toward addressing this challenge, we explored pi-conjugated water-soluble macrocycles with hydrophobic pockets. A new family of o-terphenyl-based macrocycles, TP[n] (n = 2-8) was synthesized using the Yamamoto reaction. Macrocycles up to the octamer, TP[2]-TP[8], were isolated and fully characterized. X-ray studies reveal that these macrocycles can form folded conformations stabilized by stacking interactions. TP[3] was identified as the most selective host for Phe with an affinity of 7 x 103 M-1 in water. The hosts, composed of 2-5 subunits were found to effectively inhibit protein aggregation according to the fluorescence assay using thioflavin T. The discovery of the new family of macrocycles paves the way for designing hosts with diverse architectures, precisely tailored geometries, and optimized binding properties capable of targeting not only individual amino acids but also entire protein surfaces.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"12 1","pages":"e25972"},"PeriodicalIF":16.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471501","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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