Jacques Lalevee, Ji Feng, Tong Gao, Fabrice Morlet-Savary, Michael Schmitt, Celine Dietlin, Jing Zhang, Pu Xiao, Frédéric Dumur, Xiaotong Peng
This study presents the development and evaluation of five dyes with varying conjugated energy levels and donor-π-acceptor (D-π-A) structures as photoinitiators for free radical polymerization. Their photoinitiation efficiencies are systematically assessed under both visible-light LED and sunlight. Notably, the conversions reach up to 81% within just 30 s under sunlight, demonstrating the ultra-fast and efficient polymerization capabilities of the dyes. The efficient electron transfer is facilitated by the D-π-A structure, where the conjugation is reduced or interrupted by the high distortion between the electron-withdrawing and the electron-releasing units. This distortion can prevent the overlap of frontier molecular orbitals, decreasing the energy difference between the ground state and the excited state of dyes, thereby enhancing the electron transfer reactivity with additives. Additionally, we propose a chemical mechanism for the electron transfer reaction in the three-component systems. The study also explores the application of naphtho[2,3-d]thiazole-4,9-dione-based dyes as donors in additive manufacturing demonstrating their effectiveness in three different 3D printing technologies, i.e. direct laser writing (DLW), digital light processing (DLP), and liquid crystal display (LCD). These three-component formulations achieve high-precision 3D printed objects, with detailed characterization and comparison of the resulting structures.
{"title":"Donor-π-Acceptor Photoinitiators for High-Efficiency Visible LED and Sunlight Polymerization and High-Precision 3D Printing","authors":"Jacques Lalevee, Ji Feng, Tong Gao, Fabrice Morlet-Savary, Michael Schmitt, Celine Dietlin, Jing Zhang, Pu Xiao, Frédéric Dumur, Xiaotong Peng","doi":"10.1002/anie.202425198","DOIUrl":"https://doi.org/10.1002/anie.202425198","url":null,"abstract":"This study presents the development and evaluation of five dyes with varying conjugated energy levels and donor-π-acceptor (D-π-A) structures as photoinitiators for free radical polymerization. Their photoinitiation efficiencies are systematically assessed under both visible-light LED and sunlight. Notably, the conversions reach up to 81% within just 30 s under sunlight, demonstrating the ultra-fast and efficient polymerization capabilities of the dyes. The efficient electron transfer is facilitated by the D-π-A structure, where the conjugation is reduced or interrupted by the high distortion between the electron-withdrawing and the electron-releasing units. This distortion can prevent the overlap of frontier molecular orbitals, decreasing the energy difference between the ground state and the excited state of dyes, thereby enhancing the electron transfer reactivity with additives. Additionally, we propose a chemical mechanism for the electron transfer reaction in the three-component systems. The study also explores the application of naphtho[2,3-d]thiazole-4,9-dione-based dyes as donors in additive manufacturing demonstrating their effectiveness in three different 3D printing technologies, i.e. direct laser writing (DLW), digital light processing (DLP), and liquid crystal display (LCD). These three-component formulations achieve high-precision 3D printed objects, with detailed characterization and comparison of the resulting structures.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"23 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867048","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}
Nickel-based perovskite oxides are identified as promising candidates for oxygen evolution reaction (OER) catalysts in view of their low cost, highly tunable structure, and potential high activity. However, the performance and catalyst design are hindered by their sluggish surface reconstruction kinetics. We introduce a ferric ion pre-etching strategy to enhance the surface reconstruction of typical LaNiO3. The hydrolysis of ferric ions generates hydrated protons that corrode the La-O terminal sites, inducing lattice distortion and lowering the energy barrier for reconstruction. Concurrently, ferric ion substitution for Ni creates crucial active sites after OER reconstruction, and enables the low-activity LaNiO3 to become highly active and superior to the benchmark RuO2 and NiFe LDHs. In situ X-ray absorption spectroscopy (XAS) and in situ Raman spectroscopy reveal substantial surface transformation from corner-sharing to edge-sharing NiO6 at 1.43 V vs. reversible hydrogen electrode in the surface pre-etched sample (LNFeⅢ-spe). This reconstruction is initiated by the lattice oxygen mechanism and transitions to the adsorbate evolution mechanism, underscoring the transformation of distinct OER mechanisms.
{"title":"Surface Transformation in Lanthanum Nickelate for Enhanced Oxygen Evolution Catalysis","authors":"Jia-Wei Zhao, Kaihang Yue, Lili Wu, Jiarui Yang, Deyan Luan, Xitian Zhang, Xiong-Wen (David) Lou","doi":"10.1002/anie.202507144","DOIUrl":"https://doi.org/10.1002/anie.202507144","url":null,"abstract":"Nickel-based perovskite oxides are identified as promising candidates for oxygen evolution reaction (OER) catalysts in view of their low cost, highly tunable structure, and potential high activity. However, the performance and catalyst design are hindered by their sluggish surface reconstruction kinetics. We introduce a ferric ion pre-etching strategy to enhance the surface reconstruction of typical LaNiO3. The hydrolysis of ferric ions generates hydrated protons that corrode the La-O terminal sites, inducing lattice distortion and lowering the energy barrier for reconstruction. Concurrently, ferric ion substitution for Ni creates crucial active sites after OER reconstruction, and enables the low-activity LaNiO3 to become highly active and superior to the benchmark RuO2 and NiFe LDHs. In situ X-ray absorption spectroscopy (XAS) and in situ Raman spectroscopy reveal substantial surface transformation from corner-sharing to edge-sharing NiO6 at 1.43 V vs. reversible hydrogen electrode in the surface pre-etched sample (LNFeⅢ-spe). This reconstruction is initiated by the lattice oxygen mechanism and transitions to the adsorbate evolution mechanism, underscoring the transformation of distinct OER mechanisms.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"74 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872505","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}
Jonas Futter, Leon Ferdinand Richter, Stefanie Hörl, Bernhard Rieger, Moritz Kränzlein
This study presents a phosgene- and isocyanate-free route for the synthesis of polyurethanes using (R)-limonene as a bio-based starting material. The synthesis of the cyclic limonene-based carbamate monomer LU is achieved in high yields using dimethyl carbonate as a sustainable, less hazardous phosgene surrogate and is verified by NMR, SC-XRD, ESI-MS, GC-MS, and elemental analysis. Polymerizations were carried out by coordinative ring-opening polymerization. Sn(Oct)2showed the best catalytic performance, achieving up to 93% conversion with molecular weights up to 16.0 kg/mol at a polydispersity of 1.5. Detailed mechanistic insights were obtained by kinetic studies, end group determination via ESI-MS and stoichiometric ninhydrin experiments, N-H methylation of LU, kinetic isotope experiments, and 119Sn NMR measurements. The resulting semi-crystalline polyurethane exhibits promising thermal properties, including a decomposition temperature of 252 °C, and a glass transition temperature above 150 °C. Depolymerization in solution was achieved in high yield using the same catalyst. This work describes a coordinative ring-opening polymerization approach using a terpene-based carbamate as monomer, an important step towards bio-based polyurethanes.
{"title":"Coordinative Ring-Opening Polymerization of Limonene Carbamate towards Phosgene- and Isocyanate-Free Polyurethane","authors":"Jonas Futter, Leon Ferdinand Richter, Stefanie Hörl, Bernhard Rieger, Moritz Kränzlein","doi":"10.1002/anie.202502727","DOIUrl":"https://doi.org/10.1002/anie.202502727","url":null,"abstract":"This study presents a phosgene- and isocyanate-free route for the synthesis of polyurethanes using (R)-limonene as a bio-based starting material. The synthesis of the cyclic limonene-based carbamate monomer LU is achieved in high yields using dimethyl carbonate as a sustainable, less hazardous phosgene surrogate and is verified by NMR, SC-XRD, ESI-MS, GC-MS, and elemental analysis. Polymerizations were carried out by coordinative ring-opening polymerization. Sn(Oct)2showed the best catalytic performance, achieving up to 93% conversion with molecular weights up to 16.0 kg/mol at a polydispersity of 1.5. Detailed mechanistic insights were obtained by kinetic studies, end group determination via ESI-MS and stoichiometric ninhydrin experiments, N-H methylation of LU, kinetic isotope experiments, and 119Sn NMR measurements. The resulting semi-crystalline polyurethane exhibits promising thermal properties, including a decomposition temperature of 252 °C, and a glass transition temperature above 150 °C. Depolymerization in solution was achieved in high yield using the same catalyst. This work describes a coordinative ring-opening polymerization approach using a terpene-based carbamate as monomer, an important step towards bio-based polyurethanes.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"8 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872592","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}
Covalent drugs have experienced a revival in recent decades due to their advantageous pharmacodynamic profiles and targeting of “undruggable” proteins. However, balancing selectivity, reactivity, and potency is essential for the safe and effective drugs. Here we employ a cell-selective bioorthogonal prodrug design to enhance the selectivity for covalent inhibitors without compromising the reactivity and potency. The upregulation of phosphatase and integrin facilitates the formation of enzyme-instructed supramolecular assemblies (EISA) on cancer cell membrane. These assemblies localize bioorthogonal reaction handles tetrazine (Tz) which liberate Melphalan from its bioorthogonal prodrug TCO-Mel. The TCO modification disrupts the LAT1 mediated transportation, reducing cellular permeability of TCO-Mel and the corresponding cytotoxicity to normal cells. While the cell-selective on-membrane assemblies directed prodrug activation restores Melphalan influx to inhibit cancer cell growth. This prodrug activation strategy further demonstrates potent tumor suppression with satisfactory biocompatibility in vivo. Overall, we extend the scope of bioorthogonal prodrug design for covalent drugs via regulating cellular influx of active pharmaceutical ingredients (APIs).
{"title":"On-Membrane Supramolecular Assemblies Serving as Bioorthogonal Gating for Melphalan","authors":"Hanlin Xu, Qingxin Yao, Xiaoqian Hu, Debin Zheng, Chao Ren, Zhibin Ren, Yuan Gao","doi":"10.1002/anie.202502922","DOIUrl":"https://doi.org/10.1002/anie.202502922","url":null,"abstract":"Covalent drugs have experienced a revival in recent decades due to their advantageous pharmacodynamic profiles and targeting of “undruggable” proteins. However, balancing selectivity, reactivity, and potency is essential for the safe and effective drugs. Here we employ a cell-selective bioorthogonal prodrug design to enhance the selectivity for covalent inhibitors without compromising the reactivity and potency. The upregulation of phosphatase and integrin facilitates the formation of enzyme-instructed supramolecular assemblies (EISA) on cancer cell membrane. These assemblies localize bioorthogonal reaction handles tetrazine (Tz) which liberate Melphalan from its bioorthogonal prodrug TCO-Mel. The TCO modification disrupts the LAT1 mediated transportation, reducing cellular permeability of TCO-Mel and the corresponding cytotoxicity to normal cells. While the cell-selective on-membrane assemblies directed prodrug activation restores Melphalan influx to inhibit cancer cell growth. This prodrug activation strategy further demonstrates potent tumor suppression with satisfactory biocompatibility in vivo. Overall, we extend the scope of bioorthogonal prodrug design for covalent drugs via regulating cellular influx of active pharmaceutical ingredients (APIs).","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"7 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866891","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}
As a 4d–transition metal, the spin state of Pd is extremely difficult to directly regulate for the optimized d orbital states owing to the strong spin–orbit coupling effect and further extended d orbital. Herein, we devise "spin–selective electron donation" strategy to tune specific d orbital electrons of Pd inspired by Dewar−Chatt−Duncanson model theory. Co−S−Pd bridges with different spin–states of CoIII have been constructed in a series of Pd–PdS2–Cox HNSs with tunable Co content. Experiments and theoretical calculations indicate that low-spin CoIII (t2g6eg0) with fully occupied t2g orbitals and empty dz2 orbital can accurately alter the dz2 electron of Pd by σ–donation via Co−S−Pd bridge. In contrast, unfilled dxy orbital of high-spin CoIII (t2g5eg1) is essential for controlling the dxy electron of Pd via π–donation. Benefiting from dz2 state optimization by σ–donation, Pd–PdS2–Co4.0 delivers superior performance towards various bio–alcohols (ethanol, ethylene glycol and glycerol) with enhanced C−C bond cleavage. Furthermore, coupling glycerol oxidation reaction with CO2 reduction reaction (GOR||CO2RR), the electricity consumption of GOR||CO2RR drops 46.4% compared to the state−of−art system (OER||CO2RR). Moreover, anodic Faraday efficiency (FE) of formic acid can be attainable more than 90% at low voltage region.
{"title":"Enhancing C–C Bond Cleavage of Glycerol Electrooxidation through Spin-selective Electron Donation in Pd–PdS2–Cox Heterostructural Nanosheets","authors":"Pei Liu, Hao Ma, Yuchen Qin, Junjun Li, Fengwang Li, Jinyu Ye, Qiudi Guo, Ning Su, Chao Gao, Lixia Xie, Xia Sheng, Shiju Zhao, Guangce Jiang, Yunlai Ren, Yuanmiao Sun, Zhicheng Zhang","doi":"10.1002/anie.202506032","DOIUrl":"https://doi.org/10.1002/anie.202506032","url":null,"abstract":"As a 4d–transition metal, the spin state of Pd is extremely difficult to directly regulate for the optimized d orbital states owing to the strong spin–orbit coupling effect and further extended d orbital. Herein, we devise \"spin–selective electron donation\" strategy to tune specific d orbital electrons of Pd inspired by Dewar−Chatt−Duncanson model theory. Co−S−Pd bridges with different spin–states of CoIII have been constructed in a series of Pd–PdS2–Cox HNSs with tunable Co content. Experiments and theoretical calculations indicate that low-spin CoIII (t2g6eg0) with fully occupied t2g orbitals and empty dz2 orbital can accurately alter the dz2 electron of Pd by σ–donation via Co−S−Pd bridge. In contrast, unfilled dxy orbital of high-spin CoIII (t2g5eg1) is essential for controlling the dxy electron of Pd via π–donation. Benefiting from dz2 state optimization by σ–donation, Pd–PdS2–Co4.0 delivers superior performance towards various bio–alcohols (ethanol, ethylene glycol and glycerol) with enhanced C−C bond cleavage. Furthermore, coupling glycerol oxidation reaction with CO2 reduction reaction (GOR||CO2RR), the electricity consumption of GOR||CO2RR drops 46.4% compared to the state−of−art system (OER||CO2RR). Moreover, anodic Faraday efficiency (FE) of formic acid can be attainable more than 90% at low voltage region.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"28 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872510","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}
Volker Klein, Florian Schuster, Jonas Amthor, Harald Maid, Prabhakar Bijalwan, Fahmi Himo, Stefano Santoro, Svetlana B. Tsogoeva
The transamination reaction, which involves the conversion of one amine to another, traditionally relies on biological enzyme catalysts. Although chemists have recently developed a few transition metal-catalyzed methods, mimicking these enzymes to interconvert amine groups in acyclic substrates via transamination metathesis of a single C(sp2)–N bond, transamination of cyclic tertiary amines has remained a challenge in synthetic chemistry. Here, we present the development of organoautocatalyzed transamination metathesis of two C(sp2)–N bonds in a cyclic substrate that allows for the challenging transformation to take place with up to 95% yield under exceptionally mild reaction conditions at room temperature without external catalysts and/or additives. The reaction mechanism has been studied in detail through time-resolved 1H-NMR, 2D NMR, and computational methods. Remarkably, in situ-formed pyrrolidinium salt acts as a hydrogen bond donor (HBD) organoautocatalyst in this multi-step domino process. The new organoautocatalyzed methodology gives environmentally friendly, atom-economical, straightforward, and rapid access to N-substituted 3,5-dinitro-1,4-dihydropyridines (DNDHPs), thus offering facile entry to privileged bioactive compounds.
{"title":"Development of an Organoautocatalyzed Double σ-Bond C(sp2)-N Transamination Metathesis Reaction","authors":"Volker Klein, Florian Schuster, Jonas Amthor, Harald Maid, Prabhakar Bijalwan, Fahmi Himo, Stefano Santoro, Svetlana B. Tsogoeva","doi":"10.1002/anie.202505275","DOIUrl":"https://doi.org/10.1002/anie.202505275","url":null,"abstract":"The transamination reaction, which involves the conversion of one amine to another, traditionally relies on biological enzyme catalysts. Although chemists have recently developed a few transition metal-catalyzed methods, mimicking these enzymes to interconvert amine groups in acyclic substrates via transamination metathesis of a single C(sp2)–N bond, transamination of cyclic tertiary amines has remained a challenge in synthetic chemistry. Here, we present the development of organoautocatalyzed transamination metathesis of two C(sp2)–N bonds in a cyclic substrate that allows for the challenging transformation to take place with up to 95% yield under exceptionally mild reaction conditions at room temperature without external catalysts and/or additives. The reaction mechanism has been studied in detail through time-resolved 1H-NMR, 2D NMR, and computational methods. Remarkably, in situ-formed pyrrolidinium salt acts as a hydrogen bond donor (HBD) organoautocatalyst in this multi-step domino process. The new organoautocatalyzed methodology gives environmentally friendly, atom-economical, straightforward, and rapid access to N-substituted 3,5-dinitro-1,4-dihydropyridines (DNDHPs), thus offering facile entry to privileged bioactive compounds.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"35 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866887","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}
Fritz Paulus, Corinna Heusel, Marc Jaspers, Lilli M. Amrehn, Florian Schreiner, Debanjan Rana, Constantin G. Daniliuc, Michael Ryan Hansen, Frank Glorius
closo-Carboranes are icosahedral carbon-boron clusters with unique properties and broad applicability. They particularly stand out in the context of drug development as privileged structural motifs for boron neutron capture therapy (BNCT) and as highly hydrophobic bioisosteres for the rotational volume of phenyl rings. Herein, we unveil the synthesis of N-protected carboranyl analogs of β-arylethylamines – widely found structural motifs in biologically active molecules – via a one-step alkene difunctionalization approach. Key for our success were the enabling mechanistic characteristics of energy transfer catalysis which we used for the first time to generate carboranyl radicals. Downstream modifications gave a series of analogs of amino acids and known N-methyl-d-aspartate receptor (NMDAR) antagonists.
闭碳硼烷是二十面体碳硼团簇，具有独特的性质和广泛的适用性。作为硼中子俘获疗法（BNCT）的重要结构基团，以及作为苯基环旋转体积的高疏水生物助推器，它们在药物开发方面尤为突出。在这里，我们通过一步烯双官能化方法，揭示了β-芳基乙胺（生物活性分子中广泛存在的结构基团）的 N 保护硼烷类似物的合成过程。我们成功的关键在于能量转移催化的有利机械特性，我们首次利用能量转移催化生成硼烷自由基。通过下游修饰，我们得到了一系列氨基酸类似物和已知的 N-甲基-d-天冬氨酸受体 (NMDAR) 拮抗剂。
{"title":"closo-Carboranyl Analogs of β-Arylethylamines: Direct Synthesis from Alkenes via EnT-Catalysis","authors":"Fritz Paulus, Corinna Heusel, Marc Jaspers, Lilli M. Amrehn, Florian Schreiner, Debanjan Rana, Constantin G. Daniliuc, Michael Ryan Hansen, Frank Glorius","doi":"10.1002/anie.202504793","DOIUrl":"https://doi.org/10.1002/anie.202504793","url":null,"abstract":"closo-Carboranes are icosahedral carbon-boron clusters with unique properties and broad applicability. They particularly stand out in the context of drug development as privileged structural motifs for boron neutron capture therapy (BNCT) and as highly hydrophobic bioisosteres for the rotational volume of phenyl rings. Herein, we unveil the synthesis of N-protected carboranyl analogs of β-arylethylamines – widely found structural motifs in biologically active molecules – via a one-step alkene difunctionalization approach. Key for our success were the enabling mechanistic characteristics of energy transfer catalysis which we used for the first time to generate carboranyl radicals. Downstream modifications gave a series of analogs of amino acids and known N-methyl-d-aspartate receptor (NMDAR) antagonists.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"28 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872513","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}
Although several diazotases have been recently reported, the details of the reaction mechanism are not yet understood. In this study, we investigated the mechanism of CmaA6, an ATP-dependent diazotase that catalyzes the diazotization of 3-aminocoumaric acid using nitrous acid. X-ray crystallography and cryogenic electron microscopy-single particle analysis revealed CmaA6 structures in the substrate-free and AMP-binding states. Kinetic analysis suggested that CmaA6 catalyzes diazotization via a sequential reaction mechanism in which three substrates (nitrous acid, ATP, and 3-aminocoumaric acid) are simultaneously bound in the reaction pocket. The nitrous acid- and 3-aminocoumaric acid-binding sites were predicted based on the AMP-binding state and confirmed by site-directed mutagenesis. In addition, computational analysis revealed a tunnel for 3-aminocoumaric acid to enter the reaction pocket, which was advantageous for the sequential reaction mechanism. This study provides important insights into the catalytic mechanism of diazotization in natural product biosynthesis.
{"title":"Structural Basis for the Catalytic Mechanism of ATP-Dependent Diazotase CmaA6","authors":"Seiji Kawai, Masayuki Karasawa, Yoshitaka Moriwaki, Tohru Terada, Yohei Katsuyama, Yasuo Ohnishi","doi":"10.1002/anie.202505851","DOIUrl":"https://doi.org/10.1002/anie.202505851","url":null,"abstract":"Although several diazotases have been recently reported, the details of the reaction mechanism are not yet understood. In this study, we investigated the mechanism of CmaA6, an ATP-dependent diazotase that catalyzes the diazotization of 3-aminocoumaric acid using nitrous acid. X-ray crystallography and cryogenic electron microscopy-single particle analysis revealed CmaA6 structures in the substrate-free and AMP-binding states. Kinetic analysis suggested that CmaA6 catalyzes diazotization via a sequential reaction mechanism in which three substrates (nitrous acid, ATP, and 3-aminocoumaric acid) are simultaneously bound in the reaction pocket. The nitrous acid- and 3-aminocoumaric acid-binding sites were predicted based on the AMP-binding state and confirmed by site-directed mutagenesis. In addition, computational analysis revealed a tunnel for 3-aminocoumaric acid to enter the reaction pocket, which was advantageous for the sequential reaction mechanism. This study provides important insights into the catalytic mechanism of diazotization in natural product biosynthesis.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872504","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}
Hua Sun, Jianan Fan, Rong Fan, Po Sun, Shifan Wang, Danfeng Wang, Peiyang Gu, Wenyi Tan, Yongfa Zhu
Achieving ultrafast dissociation of photogenerated excitons and efficient charge transport within the photocatalyst is a fundamental issue. Additionally, enhancing the interaction between semiconductors and water is crucial for efficient photocatalytic water splitting. Herein, we synthesized a carboxylate-based hydrophilic polymer, hPTB7-Th. Exposed carboxylates enhance semiconductor-water interfacial compatibility, reducing contact resistance and accelerating charge transfer kinetics. Furthermore, the carboxylate substitution shifts polarity centers, amplifying the molecular dipole moment by 10-fold. This induces a giant built-in electric field, enabling ultrafast electron-transfer process (ca. 0.31 ps) in the hPTB7-Th:PCBM bulk heterojunction. Consequently, the hPTB7-Th:PCBM-based bulk heterojunction nanoparticles exhibit excellent photocatalytic activity, achieving an optimal hydrogen evolution rate of 111.5 mmol g-1 h-1, four times over the ester-based counterpart (PTB7-Th:PCBM). Moreover, the electrostatic stability imparted by the carboxylates endows hPTB7-Th:PCBM with outstanding operational stability, maintaining 81% of its initial hydrogen evolution rate after 100 h operation. This result places it among the state-of-the-art organic photovoltaic bulk heterojunction photocatalysts in terms of stability. This work establishes a molecular engineering strategy for high-performance bulk heterojunction photocatalysts, emphasizing synergistic optimization of hydrophilicity, dipole engineering, and interfacial dynamics.
{"title":"A Carboxylate-based Hydrophilic Organic Photovoltaic Catalyst with a Large Molecular Dipole Moment for High-Performance Photocatalytic Hydrogen Evolution","authors":"Hua Sun, Jianan Fan, Rong Fan, Po Sun, Shifan Wang, Danfeng Wang, Peiyang Gu, Wenyi Tan, Yongfa Zhu","doi":"10.1002/anie.202503792","DOIUrl":"https://doi.org/10.1002/anie.202503792","url":null,"abstract":"Achieving ultrafast dissociation of photogenerated excitons and efficient charge transport within the photocatalyst is a fundamental issue. Additionally, enhancing the interaction between semiconductors and water is crucial for efficient photocatalytic water splitting. Herein, we synthesized a carboxylate-based hydrophilic polymer, hPTB7-Th. Exposed carboxylates enhance semiconductor-water interfacial compatibility, reducing contact resistance and accelerating charge transfer kinetics. Furthermore, the carboxylate substitution shifts polarity centers, amplifying the molecular dipole moment by 10-fold. This induces a giant built-in electric field, enabling ultrafast electron-transfer process (ca. 0.31 ps) in the hPTB7-Th:PCBM bulk heterojunction. Consequently, the hPTB7-Th:PCBM-based bulk heterojunction nanoparticles exhibit excellent photocatalytic activity, achieving an optimal hydrogen evolution rate of 111.5 mmol g-1 h-1, four times over the ester-based counterpart (PTB7-Th:PCBM). Moreover, the electrostatic stability imparted by the carboxylates endows hPTB7-Th:PCBM with outstanding operational stability, maintaining 81% of its initial hydrogen evolution rate after 100 h operation. This result places it among the state-of-the-art organic photovoltaic bulk heterojunction photocatalysts in terms of stability. This work establishes a molecular engineering strategy for high-performance bulk heterojunction photocatalysts, emphasizing synergistic optimization of hydrophilicity, dipole engineering, and interfacial dynamics.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"33 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866883","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}
Palina Nepachalovich, Stefano Bonciarelli, Gabriele Lombardi Bendoula, Jenny Desantis, Michela Eleuteri, Christoph Thiele, Laura Goracci, Maria Fedorova
Tracing lipid metabolism in mammalian cells presents a significant technological challenge due to the vast structural diversity of lipids involved in multiple metabolic routes. Biorthogonal approaches based on click chemistry have revolutionized analytical performance in lipid tracing. When adapted for mass spectrometry (MS), it enables highly specific and sensitive analyses of lipid transformations at the lipidome scale. Here, we advance this approach by integrating liquid chromatography (LC) prior to MS detection and developing a software-assisted workflow for high-throughput data processing. LC separation resolved labelled and unmodified lipids, enabling qualitative and quantitative analysis of both lipidome fractions, as well as isomeric lipid species. Using synthetic standards and endogenously produced alkyne lipids, we characterized LC-MS behaviour, including preferential adduct formation and extent of in-source fragmentation. Specific fragmentation rules derived from tandem MS experiments for 23 lipid subclasses, were implemented in Lipostar2 software for high-throughput annotation and quantification of labelled lipids. Applying this platform, we traced metabolic pathways of palmitic and oleic acid alkynes, revealing distinct lipid incorporation patterns and metabolic bottlenecks. Altogether, here we provide integrated analytical and bioinformatics platform for high-throughput tracing of lipid metabolism using LC-MS workflow.
{"title":"LC-MS and High-Throughput Data Processing Solutions for Lipid Metabolic Tracing Using Biorthogonal Click Chemistry","authors":"Palina Nepachalovich, Stefano Bonciarelli, Gabriele Lombardi Bendoula, Jenny Desantis, Michela Eleuteri, Christoph Thiele, Laura Goracci, Maria Fedorova","doi":"10.1002/anie.202501884","DOIUrl":"https://doi.org/10.1002/anie.202501884","url":null,"abstract":"Tracing lipid metabolism in mammalian cells presents a significant technological challenge due to the vast structural diversity of lipids involved in multiple metabolic routes. Biorthogonal approaches based on click chemistry have revolutionized analytical performance in lipid tracing. When adapted for mass spectrometry (MS), it enables highly specific and sensitive analyses of lipid transformations at the lipidome scale. Here, we advance this approach by integrating liquid chromatography (LC) prior to MS detection and developing a software-assisted workflow for high-throughput data processing. LC separation resolved labelled and unmodified lipids, enabling qualitative and quantitative analysis of both lipidome fractions, as well as isomeric lipid species. Using synthetic standards and endogenously produced alkyne lipids, we characterized LC-MS behaviour, including preferential adduct formation and extent of in-source fragmentation. Specific fragmentation rules derived from tandem MS experiments for 23 lipid subclasses, were implemented in Lipostar2 software for high-throughput annotation and quantification of labelled lipids. Applying this platform, we traced metabolic pathways of palmitic and oleic acid alkynes, revealing distinct lipid incorporation patterns and metabolic bottlenecks. Altogether, here we provide integrated analytical and bioinformatics platform for high-throughput tracing of lipid metabolism using LC-MS workflow.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"48 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867050","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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