We evaluate the ability of machine learning to predict whether a hypothetical crystal structure can be synthesized and explain those predictions to scientists. Fine-tuned large language models (LLMs) trained on a human-readable text description of the target crystal structure perform comparably to previous bespoke convolutional graph neural network methods, but better prediction quality can be achieved by training a positive-unlabeled learning model on a text-embedding representation of the structure. An LLM-based workflow can then be used to generate human-readable explanations for the types of factors governing synthesizability, extract the underlying physical rules, and assess the veracity of those rules. These explanations can guide chemists in modifying or optimizing non-synthesizable hypothetical structures to make them more feasible for materials design.
{"title":"Explainable Synthesizability Prediction of Inorganic Crystal Polymorphs using Large Language Models","authors":"Seongmin Kim, Joshua Schrier, Yousung Jung","doi":"10.1002/anie.202423950","DOIUrl":"https://doi.org/10.1002/anie.202423950","url":null,"abstract":"We evaluate the ability of machine learning to predict whether a hypothetical crystal structure can be synthesized and explain those predictions to scientists. Fine-tuned large language models (LLMs) trained on a human-readable text description of the target crystal structure perform comparably to previous bespoke convolutional graph neural network methods, but better prediction quality can be achieved by training a positive-unlabeled learning model on a text-embedding representation of the structure. An LLM-based workflow can then be used to generate human-readable explanations for the types of factors governing synthesizability, extract the underlying physical rules, and assess the veracity of those rules. These explanations can guide chemists in modifying or optimizing non-synthesizable hypothetical structures to make them more feasible for materials design.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"22 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401706","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}
Zhengdong Wu, Siqiang Fang, Jiajia He, Jixing Che, Zanjiao Liu, Xin Wei, Zhishan Su, Tianli Wang
Planar chiral [2.2]paracyclophanes, particularly pseudo-disubstituted derivatives, are privileged scaffolds for chiral ligands and catalysts in asymmetric synthesis and have widespread applications in materials science. However, catalytic asymmetric approaches for the enantioselective synthesis of pseudo-disubstituted [2.2]paracyclophanes remain underexplored. In this study, we introduce a novel class of peptide-iminophosphorane organosuperbases to induce planar chirality in spatially stacked [2.2]paracyclophanes. This efficient protocol enables the enantioselective synthesis of a diverse array of structurally distinct pseudo-gem, pseudo-ortho, and pseudo-para [2.2]paracyclophanes, achieving high yields and excellent enantioselectivities via desymmetrization or kinetic resolution. Moreover, the products can be readily diversified through various functional group transformations. Mechanistic investigations provide valuable insights into the unique stereocontrol exhibited by this peptide-iminophosphorane catalytic system.
{"title":"Desymmetrization/Kinetic Resolution of Planar Chiral [2.2]Paracyclophanes by Bioinspired Peptide-Iminophosphorane Catalysis","authors":"Zhengdong Wu, Siqiang Fang, Jiajia He, Jixing Che, Zanjiao Liu, Xin Wei, Zhishan Su, Tianli Wang","doi":"10.1002/anie.202423702","DOIUrl":"https://doi.org/10.1002/anie.202423702","url":null,"abstract":"Planar chiral [2.2]paracyclophanes, particularly pseudo-disubstituted derivatives, are privileged scaffolds for chiral ligands and catalysts in asymmetric synthesis and have widespread applications in materials science. However, catalytic asymmetric approaches for the enantioselective synthesis of pseudo-disubstituted [2.2]paracyclophanes remain underexplored. In this study, we introduce a novel class of peptide-iminophosphorane organosuperbases to induce planar chirality in spatially stacked [2.2]paracyclophanes. This efficient protocol enables the enantioselective synthesis of a diverse array of structurally distinct pseudo-gem, pseudo-ortho, and pseudo-para [2.2]paracyclophanes, achieving high yields and excellent enantioselectivities via desymmetrization or kinetic resolution. Moreover, the products can be readily diversified through various functional group transformations. Mechanistic investigations provide valuable insights into the unique stereocontrol exhibited by this peptide-iminophosphorane catalytic system.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"11 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401703","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}
Flexible metal-organic frameworks (MOFs) are promising candidates for adsorptive separations, but achieving a balance among flexibility, adsorption capacity, and selectivity remains challenging. Herein, we report a novel flexible MOF, Ni(bhdc)(ted)0.5 (ZUL-C6), incorporating hybrid three-dimensional alkane-bridged ligands, which realizes high-capacity molecular sieving for hexane isomer separation - a critical process in the petroleum industry. The alkyl-rich, confined pore system within the ZUL-C6 framework facilitated a strong affinity for n-hexane and 3-methylpentane. However, the narrow pore size and the constraint flexibility limited the uptake of 2,2-dimethylbutane (< 4.0 mg/g), accompanied by a high gate-opening pressure. The gating behavior was elucidated by guest-loaded single-crystal (SC) X-ray diffraction and density functional theory (DFT) simulations, which revealed a unique SC to SC transformation driven by the non-centrosymmetric rotation of the 3D bhdc linker and distortion of the metal cluster and pillar units, along with a high deformation energy barrier. As a result, ZUL-C6 exhibited not only significantly higher uptake and selectivity than the industrially used 5A molecular sieve, but also the record-high nHEX/3MP breakthrough uptake (92.8/73.9 mg/g) and unprecedented 22DMB producing time (309.2 min/g, corresponding to the productivity of 770 mmol/kg and yield of 92.8%) among reported MOFs.
{"title":"Metal-Organic Framework with Constraint Flexibility for Benchmark Separation of Hexane Isomers","authors":"Kuishan Wen, Jingyi Zhou, Tian Ke, Jinjian Li, Yuanyuan Jin, Qianglong Zhang, Zhiguo Zhang, Zongbi Bao, Qilong Ren, Qiwei Yang","doi":"10.1002/anie.202500519","DOIUrl":"https://doi.org/10.1002/anie.202500519","url":null,"abstract":"Flexible metal-organic frameworks (MOFs) are promising candidates for adsorptive separations, but achieving a balance among flexibility, adsorption capacity, and selectivity remains challenging. Herein, we report a novel flexible MOF, Ni(bhdc)(ted)0.5 (ZUL-C6), incorporating hybrid three-dimensional alkane-bridged ligands, which realizes high-capacity molecular sieving for hexane isomer separation - a critical process in the petroleum industry. The alkyl-rich, confined pore system within the ZUL-C6 framework facilitated a strong affinity for n-hexane and 3-methylpentane. However, the narrow pore size and the constraint flexibility limited the uptake of 2,2-dimethylbutane (< 4.0 mg/g), accompanied by a high gate-opening pressure. The gating behavior was elucidated by guest-loaded single-crystal (SC) X-ray diffraction and density functional theory (DFT) simulations, which revealed a unique SC to SC transformation driven by the non-centrosymmetric rotation of the 3D bhdc linker and distortion of the metal cluster and pillar units, along with a high deformation energy barrier. As a result, ZUL-C6 exhibited not only significantly higher uptake and selectivity than the industrially used 5A molecular sieve, but also the record-high nHEX/3MP breakthrough uptake (92.8/73.9 mg/g) and unprecedented 22DMB producing time (309.2 min/g, corresponding to the productivity of 770 mmol/kg and yield of 92.8%) among reported MOFs.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"7 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401892","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 Organic Frameworks (COFs) are promising in the field of photonic energy conversion. However, most efforts have been concentrated on the design of ligand geometric structures and chemical bonding relationships, while understanding the impact of stacking methods on photonic energy conversion remains a significant challenge. In this work, four COFs (1D‐COF, 1D‐MeCOF, 1D‐tBuCOF and 2D‐COF) with the same main‐chain structure but different stacking methods are designed and synthesized, using photocatalytic hydrogen evolution as a model reaction. Mortise‐tenon stacked 1D‐MeCOF exhibits far superior photocatalytic hydrogen evolution performance to other stacking methods, and it maintains high efficiency and stability in natural seawater systems. Extensive characterization demonstrates that such a unique mortise‐tenon stacking structure of 1D‐MeCOF inhibits interchain slippage, enhances π‐stacking, and maximizing light absorption capabilities. Furthermore, unidirectional carrier transport characteristics of one‐dimensional structure can generate a strong photo‐induced self‐built electric field, which acts as "self‐catalysis" to accelerate carrier transport. This work provides an effective design strategy and mechanistic insights on the stacking engineering of photonic energy conversion materials.
{"title":"“Self‐Catalysis” Acceleration of Carrier Transport in One‐Dimensional Covalent Organic Frameworks with Mortise‐Tenon Stacking","authors":"Zhe Zhang, Yuxin Liu, Yuhang Qi, Zhuochen Yu, Xiaobo Chen, Chunguang Li, Zhan Shi, Shouhua Feng","doi":"10.1002/anie.202501614","DOIUrl":"https://doi.org/10.1002/anie.202501614","url":null,"abstract":"Covalent Organic Frameworks (COFs) are promising in the field of photonic energy conversion. However, most efforts have been concentrated on the design of ligand geometric structures and chemical bonding relationships, while understanding the impact of stacking methods on photonic energy conversion remains a significant challenge. In this work, four COFs (1D‐COF, 1D‐MeCOF, 1D‐tBuCOF and 2D‐COF) with the same main‐chain structure but different stacking methods are designed and synthesized, using photocatalytic hydrogen evolution as a model reaction. Mortise‐tenon stacked 1D‐MeCOF exhibits far superior photocatalytic hydrogen evolution performance to other stacking methods, and it maintains high efficiency and stability in natural seawater systems. Extensive characterization demonstrates that such a unique mortise‐tenon stacking structure of 1D‐MeCOF inhibits interchain slippage, enhances π‐stacking, and maximizing light absorption capabilities. Furthermore, unidirectional carrier transport characteristics of one‐dimensional structure can generate a strong photo‐induced self‐built electric field, which acts as \"self‐catalysis\" to accelerate carrier transport. This work provides an effective design strategy and mechanistic insights on the stacking engineering of photonic energy conversion materials.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"7 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401421","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}
Fabricating large-area uniform thin (about 100 nm) active layer films via solution processing is still challenging to realize efficient scalable organic photovoltaic (OPV) modules. In this work, we report a method to fabricate large-area active layer films with the help of Marangoni force via engineering the surface tension of their solutions. Silicone oil was first adopted as an additive to substantially reduce surface tension of the active layer solutions from 34.8 to 20.6 mN/m. Large-area (up to 700 cm2) thin active layer films spread spontaneously on water by Marangoni force due to the increased surface tension difference between the active layer solution and water. The films were then transferred onto charge transporting layer to fabricate devices. The active layer films fabricated by Marangoni force-assisted coating (MAC) displayed power conversion efficiencies (PCE), 17.4% ± 0.3% for PM6:BTP-eC9, 17.9 ± 0.7% for D18:N3 and 16.4 ± 0.3% for PM6:QM-1. Furthermore, large-area (32.5 cm2) OPV modules were fabricated based on the MAC method with a PCE of 14.3%. This is the first example that MAC method is used to successfully fabricate efficient OPV modules via the surface tension engineering of active layer films with silicone oil used as a low surface tension additive.
{"title":"Engineering surface tension of active layer solutions to form uniform films on water surface for large-area flexible organic photovoltaic modules","authors":"Kai Feng, Xianmin Zhou, Yerun Gao, Jianping Chen, Junfeng Liu, Xinlu Liu, Qi Luo, Qijin Zhou, Zedong Xiong, Xiaoru Wang, Ming Shao, Hongwei Han, Yinhua Zhou","doi":"10.1002/anie.202420226","DOIUrl":"https://doi.org/10.1002/anie.202420226","url":null,"abstract":"Fabricating large-area uniform thin (about 100 nm) active layer films via solution processing is still challenging to realize efficient scalable organic photovoltaic (OPV) modules. In this work, we report a method to fabricate large-area active layer films with the help of Marangoni force via engineering the surface tension of their solutions. Silicone oil was first adopted as an additive to substantially reduce surface tension of the active layer solutions from 34.8 to 20.6 mN/m. Large-area (up to 700 cm2) thin active layer films spread spontaneously on water by Marangoni force due to the increased surface tension difference between the active layer solution and water. The films were then transferred onto charge transporting layer to fabricate devices. The active layer films fabricated by Marangoni force-assisted coating (MAC) displayed power conversion efficiencies (PCE), 17.4% ± 0.3% for PM6:BTP-eC9, 17.9 ± 0.7% for D18:N3 and 16.4 ± 0.3% for PM6:QM-1. Furthermore, large-area (32.5 cm2) OPV modules were fabricated based on the MAC method with a PCE of 14.3%. This is the first example that MAC method is used to successfully fabricate efficient OPV modules via the surface tension engineering of active layer films with silicone oil used as a low surface tension additive.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"13 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401699","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}
We describe the development of a nickel-catalyzed route to prepare aliphatic isocyanates via carbonylation chemistry. Unlike thermal reactions, where the affinity of Ni(0) for carbon monoxide has traditionally limited its use in carbonylations, mechanistic studies suggest that visible light excitation of a Xantphos-bound nickel catalyst can enable a radical pathway for the carbonylation of alkyl halides, while the CO-bound nickel drives the formation of a reactive acyl azide product for rapid Curtius rearrangement. Coupling this transformation with subsequent nucleophilic reactions has opened a unique and modular pathway to apply carbonylations to the synthesis of an array of diversely substituted, unsymmetrical ureas and carbamates, including those of relevance to drug design.
{"title":"A Versatile Carbonylative Approach to Ureas and Carbamates through Light Activated Nickel Catalyzed Formation of Aliphatic Isocyanates","authors":"Bruce A. Arndtsen, Cuihan Zhou, Dushyant Singh","doi":"10.1002/anie.202423519","DOIUrl":"https://doi.org/10.1002/anie.202423519","url":null,"abstract":"We describe the development of a nickel-catalyzed route to prepare aliphatic isocyanates via carbonylation chemistry. Unlike thermal reactions, where the affinity of Ni(0) for carbon monoxide has traditionally limited its use in carbonylations, mechanistic studies suggest that visible light excitation of a Xantphos-bound nickel catalyst can enable a radical pathway for the carbonylation of alkyl halides, while the CO-bound nickel drives the formation of a reactive acyl azide product for rapid Curtius rearrangement. Coupling this transformation with subsequent nucleophilic reactions has opened a unique and modular pathway to apply carbonylations to the synthesis of an array of diversely substituted, unsymmetrical ureas and carbamates, including those of relevance to drug design.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"23 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401705","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}
Alexandra Tsouka, Yanyan Fu, Manuel G. Ricardo, Peter H. Seeberger, Yue Wang, Gerald B. Pier, Detlef Schuppan, Louis Boon, Jan Maarten van Dijl, Maria C. Bolling, Girbe Buist, Felix F Loeffler, Jon D. Laman
Peptidoglycan (PGN) is a complex biopolymer crucial for cell wall integrity and function of all bacterial species. While the strong inflammatory properties of PGN and its derived muropeptides are well-documented in human innate immune responses, adaptive immunity, including antibody responses to PGN, remain inadequately characterized. Microarray technology represents a cost- and time-efficient method for studying such interactions. Our laser-based technology enables the high-throughput synthesis of biomolecules on functionalized glass slides. Here, this on-chip synthesis was developed for PGN fragments, to generate a variety of 216 stem peptides and attach six different glycan moieties that are major structural components of bacterial cell walls. Thereby, 864 PGN fragments from different Gram-negative and Gram-positive species were generated. The arrays were validated with four different monoclonal antibodies against PGN or poly-N-acetyl glucosamine and identified their epitopes. Finally, proof of concept for antibody profiling in patient samples was performed by comparing a panel of well-characterized plasma samples of epidermolysis bullosa (EB) patients suffering from (chronic) wounds with Staphylococcus aureus infection. EB patients show an increased response to the muramyl dipeptide. Therefore, this novel high-throughput PGN glycopeptide microarray technology promises to identify distinct antibody profiles against human microbiomes in diseases, notably in those involving the intestine.
{"title":"Synthetic High-Throughput Microarrays of Peptidoglycan Fragments as a Novel Sero-Diagnostic Tool for Patient Antibody Profiling","authors":"Alexandra Tsouka, Yanyan Fu, Manuel G. Ricardo, Peter H. Seeberger, Yue Wang, Gerald B. Pier, Detlef Schuppan, Louis Boon, Jan Maarten van Dijl, Maria C. Bolling, Girbe Buist, Felix F Loeffler, Jon D. Laman","doi":"10.1002/anie.202420874","DOIUrl":"https://doi.org/10.1002/anie.202420874","url":null,"abstract":"Peptidoglycan (PGN) is a complex biopolymer crucial for cell wall integrity and function of all bacterial species. While the strong inflammatory properties of PGN and its derived muropeptides are well-documented in human innate immune responses, adaptive immunity, including antibody responses to PGN, remain inadequately characterized. Microarray technology represents a cost- and time-efficient method for studying such interactions. Our laser-based technology enables the high-throughput synthesis of biomolecules on functionalized glass slides. Here, this on-chip synthesis was developed for PGN fragments, to generate a variety of 216 stem peptides and attach six different glycan moieties that are major structural components of bacterial cell walls. Thereby, 864 PGN fragments from different Gram-negative and Gram-positive species were generated. The arrays were validated with four different monoclonal antibodies against PGN or poly-N-acetyl glucosamine and identified their epitopes. Finally, proof of concept for antibody profiling in patient samples was performed by comparing a panel of well-characterized plasma samples of epidermolysis bullosa (EB) patients suffering from (chronic) wounds with Staphylococcus aureus infection. EB patients show an increased response to the muramyl dipeptide. Therefore, this novel high-throughput PGN glycopeptide microarray technology promises to identify distinct antibody profiles against human microbiomes in diseases, notably in those involving the intestine.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"85 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401709","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}
Metal-backboned molecules have been recently explored as a new class of materials with remarkable physical and chemical properties. However, their backbones are mainly composed of Ni atoms and poses challenges in incorporating a wide range of metallic elemental species, which has severely hindered their further development. Herein, we have designed a general synthesis strategy and obtained new metal-backboned molecules with a variety of metals including Cu, Ru, Rh, Pd, Ag and Pt in the backbones through a ligand-assisted strategy under screening reaction conditions. The metal backbone with seven Cu atoms has been carefully demonstrated for the synthesis. The intriguing optical properties, electronic bandgaps and thermal properties for the metal-backboned molecules have been further explored. This work provides a new avenue on the synthesis of high-performance metal-backboned molecule materials for promising applications in the future.
{"title":"A General Strategy for the Synthesis of Metal-Backboned Molecules with Different Metals.","authors":"Yanruzhen Wu, Yifeng Zhang, Kaiwen Zeng, Xiangran Cheng, Jiatian Song, Huisheng Peng","doi":"10.1002/anie.202502327","DOIUrl":"https://doi.org/10.1002/anie.202502327","url":null,"abstract":"<p><p>Metal-backboned molecules have been recently explored as a new class of materials with remarkable physical and chemical properties. However, their backbones are mainly composed of Ni atoms and poses challenges in incorporating a wide range of metallic elemental species, which has severely hindered their further development. Herein, we have designed a general synthesis strategy and obtained new metal-backboned molecules with a variety of metals including Cu, Ru, Rh, Pd, Ag and Pt in the backbones through a ligand-assisted strategy under screening reaction conditions. The metal backbone with seven Cu atoms has been carefully demonstrated for the synthesis. The intriguing optical properties, electronic bandgaps and thermal properties for the metal-backboned molecules have been further explored. This work provides a new avenue on the synthesis of high-performance metal-backboned molecule materials for promising applications in the future.</p>","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":" ","pages":"e202502327"},"PeriodicalIF":16.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412533","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}
Qin Li, Zhaode Mu, Yuhan Dong, Zubin Ouyang, Jianli Zuo, Yijie Wu, Yuxuan Yang, Si Sun, Hongwen Liang, Lijuan Bai
Optimizing the stability and affinity of peptides in vivo is critical for their development as alternatives to approved monoclonal antibodies. In recent years, efforts in academia and industry have focused on modifying Pep2-8, a classical antagonistic peptide targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), to enhance its specificity and affinity. However, developing effective PCSK9 inhibitory peptides remains challenging, especially given the limited examples of their successful in vivo applications. Here, we designed transformable inhibitory peptide (TIP) against PCSK9 based on the modular structure of Pep2-8. Upon encountering PCSK9, TIP undergoes in situ self-assembly at the epidermal growth factor-like domain A (EGF-A) binding domain of PCSK9 to form artificial topological nanostructures (ATNs). The ATNs not only enhance peptide stability and prolong in vivo retention time but also strengthen PCSK9 binding through multivalent synergistic effects. We demonstrate that compared to Pep2-8, TIP forms ATNs which increasing its binding affinity for PCSK9 by approximately 18.7-fold in vitro. In high-fat diet mouse models, TIP significantly increase hepatic LDLR levels (2.0-fold) and reduced LDL-C and TC levels. We envision that the in situ formation of ATNs by peptides enhances in vivo stability and affinity, which offering an approach for development as antibody alternatives in clinical.
{"title":"In Situ Self-Assembly of Artificial Topological Nanostructures Enhances In Vivo Efficacy of PCSK9 Inhibitory Peptides","authors":"Qin Li, Zhaode Mu, Yuhan Dong, Zubin Ouyang, Jianli Zuo, Yijie Wu, Yuxuan Yang, Si Sun, Hongwen Liang, Lijuan Bai","doi":"10.1002/anie.202502559","DOIUrl":"https://doi.org/10.1002/anie.202502559","url":null,"abstract":"Optimizing the stability and affinity of peptides in vivo is critical for their development as alternatives to approved monoclonal antibodies. In recent years, efforts in academia and industry have focused on modifying Pep2-8, a classical antagonistic peptide targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), to enhance its specificity and affinity. However, developing effective PCSK9 inhibitory peptides remains challenging, especially given the limited examples of their successful in vivo applications. Here, we designed transformable inhibitory peptide (TIP) against PCSK9 based on the modular structure of Pep2-8. Upon encountering PCSK9, TIP undergoes in situ self-assembly at the epidermal growth factor-like domain A (EGF-A) binding domain of PCSK9 to form artificial topological nanostructures (ATNs). The ATNs not only enhance peptide stability and prolong in vivo retention time but also strengthen PCSK9 binding through multivalent synergistic effects. We demonstrate that compared to Pep2-8, TIP forms ATNs which increasing its binding affinity for PCSK9 by approximately 18.7-fold in vitro. In high-fat diet mouse models, TIP significantly increase hepatic LDLR levels (2.0-fold) and reduced LDL-C and TC levels. We envision that the in situ formation of ATNs by peptides enhances in vivo stability and affinity, which offering an approach for development as antibody alternatives in clinical.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"57 3 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401708","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}
Xiaoshuang Ma, Cong Fang, Mei Ding, Yang Zuo, Xiaoyan Sun, Shuxin Wang
Copper is the most efficient and practical electrocatalyst for the electrochemical reduction of carbon dioxide (ECR) to give multicarbon (C2+) products, but the mechanism by which such products are formed — though known to involve lattice-hydrogens — remains elusive, and the selectivity of the reaction is poor. Herein, we report the synthesis of [AuCu24(dppp)6H22]+, a copper hydride nanocluster bearing exposed Cu3H3 units in specific surface cavities, and our use of it to study the mechansim and selectivity of the reduction of CO2 to C2+ products. Results of in situ infrared spectroscopy and theoretical calculations showed that these Cu3H3 units can effectively lower the energy barrier to the formation of the *COCOH intermediate, which allowed te competition between the C1 and C2 pathways to be elucidated. Isotope labeling experiments and catalyst recrystallization studies corroborated the theoretical simulations, identifying the lattice-hydrogen (H-) in the Cu3H3 active unit as being indispensable for the formation of C2H4. The molecular design guidelines which this work has facilitated constitute a new approach towards the of copper-based catalysts that convert CO2 to C2+ products based on lattice-hydrogen engineering.
{"title":"Atomic-Level Elucidation of Lattice-Hydrogens in Copper Catalysts for Selective CO2 Electrochemical Conversion Toward C2 Products","authors":"Xiaoshuang Ma, Cong Fang, Mei Ding, Yang Zuo, Xiaoyan Sun, Shuxin Wang","doi":"10.1002/anie.202500191","DOIUrl":"https://doi.org/10.1002/anie.202500191","url":null,"abstract":"Copper is the most efficient and practical electrocatalyst for the electrochemical reduction of carbon dioxide (ECR) to give multicarbon (C2+) products, but the mechanism by which such products are formed — though known to involve lattice-hydrogens — remains elusive, and the selectivity of the reaction is poor. Herein, we report the synthesis of [AuCu24(dppp)6H22]+, a copper hydride nanocluster bearing exposed Cu3H3 units in specific surface cavities, and our use of it to study the mechansim and selectivity of the reduction of CO2 to C2+ products. Results of in situ infrared spectroscopy and theoretical calculations showed that these Cu3H3 units can effectively lower the energy barrier to the formation of the *COCOH intermediate, which allowed te competition between the C1 and C2 pathways to be elucidated. Isotope labeling experiments and catalyst recrystallization studies corroborated the theoretical simulations, identifying the lattice-hydrogen (H-) in the Cu3H3 active unit as being indispensable for the formation of C2H4. The molecular design guidelines which this work has facilitated constitute a new approach towards the of copper-based catalysts that convert CO2 to C2+ products based on lattice-hydrogen engineering.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"23 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401307","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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