Pub Date : 2025-11-21DOI: 10.1038/s41929-025-01442-2
Shusen Chen, Huimei Huang, Ning Fang
The rational design of electrocatalysts for hydrogen-involving transformations requires a detailed understanding of surface metal-hydrogen intermediates at the single-site level. Now, single-molecule fluorescence microscopy enables the direct visualization of these intermediates and reveals inter- and intra-particle heterogeneity during the hydrogen evolution reaction on Pd nanocubes.
{"title":"A single-molecule view of surface Pd–H*","authors":"Shusen Chen, Huimei Huang, Ning Fang","doi":"10.1038/s41929-025-01442-2","DOIUrl":"10.1038/s41929-025-01442-2","url":null,"abstract":"The rational design of electrocatalysts for hydrogen-involving transformations requires a detailed understanding of surface metal-hydrogen intermediates at the single-site level. Now, single-molecule fluorescence microscopy enables the direct visualization of these intermediates and reveals inter- and intra-particle heterogeneity during the hydrogen evolution reaction on Pd nanocubes.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 11","pages":"1129-1130"},"PeriodicalIF":44.6,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561888","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}
Pub Date : 2025-11-20DOI: 10.1038/s41929-025-01431-5
Kallol Mukherjee, Ayala Ben David, Hasmik Nikoghosyan, Robert Hakobyan, Vladimir Gevorgyan
Selective conversion of C–H bonds into high-value functional groups is a highly desirable process. Hydrogen atom transfer (HAT) is a powerful approach towards this goal by offering straightforward access to open-shell radical intermediates directly from R–H bonds. Recently, a subclass of photocatalysis referred to as visible-light-induced transition metal (TM) catalysis has emerged as a distinctive synthetic tool. This enables TMs to serve a dual role: capturing light energy and driving catalytic transformations. This dual functionality has been increasingly utilized to execute HAT without requiring an external photosensitizer. Although cooperative photocatalysis involving photoredox and TM catalysis contributed to early developments in this area, visible-light-induced TM catalysis offers direct and versatile approaches to C–H functionalization. In the past few years, this methodology has been extensively used to execute HAT. Here we describe the early development and recent advances of photoexcited-transition-metal-catalysed HAT processes. This Review covers the recent advances in the field of hydrogen atom transfer catalysis mediated by photoexcited transition metals without the use of external photosensitizers.
{"title":"Light-induced transition-metal-catalysed hydrogen atom transfer in organic transformations","authors":"Kallol Mukherjee, Ayala Ben David, Hasmik Nikoghosyan, Robert Hakobyan, Vladimir Gevorgyan","doi":"10.1038/s41929-025-01431-5","DOIUrl":"10.1038/s41929-025-01431-5","url":null,"abstract":"Selective conversion of C–H bonds into high-value functional groups is a highly desirable process. Hydrogen atom transfer (HAT) is a powerful approach towards this goal by offering straightforward access to open-shell radical intermediates directly from R–H bonds. Recently, a subclass of photocatalysis referred to as visible-light-induced transition metal (TM) catalysis has emerged as a distinctive synthetic tool. This enables TMs to serve a dual role: capturing light energy and driving catalytic transformations. This dual functionality has been increasingly utilized to execute HAT without requiring an external photosensitizer. Although cooperative photocatalysis involving photoredox and TM catalysis contributed to early developments in this area, visible-light-induced TM catalysis offers direct and versatile approaches to C–H functionalization. In the past few years, this methodology has been extensively used to execute HAT. Here we describe the early development and recent advances of photoexcited-transition-metal-catalysed HAT processes. This Review covers the recent advances in the field of hydrogen atom transfer catalysis mediated by photoexcited transition metals without the use of external photosensitizers.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 11","pages":"1146-1158"},"PeriodicalIF":44.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145560407","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}
Pub Date : 2025-11-18DOI: 10.1038/s41929-025-01446-y
Junhong Meng, Mithun C. Madhusudhanan, Teng Wang, Zengrui Cheng, Binzhi Zhao, Hongwei Shi, Licheng Yang, Peng Liu, Ning Jiao
The direct synthetic approach from versatile and abundantly sourced carboxylic acids to nitriles has garnered considerable attention for a long time. However, the highly unfavourable thermodynamics of this process make it challenging to achieve under mild conditions and with broad functional-group tolerance. Here, inspired by biosynthetic pathways of nitrile synthesis and urea activation, we present a mild Mg- and Pd-cocatalysed nitrile synthesis from carboxylic acids with the simple, inexpensive and readily available urea as the nitrogen source. A pathway involving nucleophilic addition of carboxylic acid to urea is supported by both mechanistic studies and density functional theory calculations. This chemistry also demonstrates efficiency for the late-stage modification of complex drugs and natural products and offers substantial opportunities for the synthesis and optimization of valuable compounds. There is growing interest in the direct conversion of carboxylic acids into nitriles. Now the authors report a mild Mg- and Pd-cocatalysed method compatible with multiple functional groups, using urea as the nitrogen source.
{"title":"Late-stage conversion of carboxylic acids to nitriles with Mg and Pd cocatalysis","authors":"Junhong Meng, Mithun C. Madhusudhanan, Teng Wang, Zengrui Cheng, Binzhi Zhao, Hongwei Shi, Licheng Yang, Peng Liu, Ning Jiao","doi":"10.1038/s41929-025-01446-y","DOIUrl":"10.1038/s41929-025-01446-y","url":null,"abstract":"The direct synthetic approach from versatile and abundantly sourced carboxylic acids to nitriles has garnered considerable attention for a long time. However, the highly unfavourable thermodynamics of this process make it challenging to achieve under mild conditions and with broad functional-group tolerance. Here, inspired by biosynthetic pathways of nitrile synthesis and urea activation, we present a mild Mg- and Pd-cocatalysed nitrile synthesis from carboxylic acids with the simple, inexpensive and readily available urea as the nitrogen source. A pathway involving nucleophilic addition of carboxylic acid to urea is supported by both mechanistic studies and density functional theory calculations. This chemistry also demonstrates efficiency for the late-stage modification of complex drugs and natural products and offers substantial opportunities for the synthesis and optimization of valuable compounds. There is growing interest in the direct conversion of carboxylic acids into nitriles. Now the authors report a mild Mg- and Pd-cocatalysed method compatible with multiple functional groups, using urea as the nitrogen source.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 12","pages":"1295-1305"},"PeriodicalIF":44.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536706","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}
Pub Date : 2025-11-18DOI: 10.1038/s41929-025-01445-z
Linfeng An, Shanshan Li, Kaiming Zhang
RNA’s regulatory and catalytic roles affect gene expression, with circular RNAs (circRNAs) emerging as a unique subclass with broad therapeutic potential. Among circRNA production methods, ribozyme-mediated circularization, especially through group I intron-based systems such as the T4 td-PIE (where PIE indicates permuted intron–exon), offers efficient in vitro synthesis. However, detailed structural insights of the T4 td intron are limited, particularly regarding circularization mechanisms. Here we use cryo-electron microscopy to resolve high-resolution structures of both linear and circular T4 td intron forms. Comparative structural analysis reveals key conformational shifts in the catalytic core, including P1ext domain loss and realignment of critical base pairs in the circular form. Additionally, we identify critical sites and interactions optimizing RNA circularization. Structure-guided mutations enhance circularization efficiency, as validated in the T4 td-PIE system and benchmarked against alternative platforms. These findings enhance our understanding of RNA circularization mechanisms and inform optimizations for large-scale circRNA production, with important implications for RNA-based therapeutics and synthetic biology. The T4 td-PIE system is a promising platform for circular RNA synthesis, but the dynamic mechanism of the T4 td group I intron during circularization remains unclear. Now, cryo-EM structures of both the linear and circular forms of the T4 td intron are solved, revealing key conformational shifts essential for RNA circularization.
{"title":"Structural insights and engineering of the T4 td intron for improved RNA circularization","authors":"Linfeng An, Shanshan Li, Kaiming Zhang","doi":"10.1038/s41929-025-01445-z","DOIUrl":"10.1038/s41929-025-01445-z","url":null,"abstract":"RNA’s regulatory and catalytic roles affect gene expression, with circular RNAs (circRNAs) emerging as a unique subclass with broad therapeutic potential. Among circRNA production methods, ribozyme-mediated circularization, especially through group I intron-based systems such as the T4 td-PIE (where PIE indicates permuted intron–exon), offers efficient in vitro synthesis. However, detailed structural insights of the T4 td intron are limited, particularly regarding circularization mechanisms. Here we use cryo-electron microscopy to resolve high-resolution structures of both linear and circular T4 td intron forms. Comparative structural analysis reveals key conformational shifts in the catalytic core, including P1ext domain loss and realignment of critical base pairs in the circular form. Additionally, we identify critical sites and interactions optimizing RNA circularization. Structure-guided mutations enhance circularization efficiency, as validated in the T4 td-PIE system and benchmarked against alternative platforms. These findings enhance our understanding of RNA circularization mechanisms and inform optimizations for large-scale circRNA production, with important implications for RNA-based therapeutics and synthetic biology. The T4 td-PIE system is a promising platform for circular RNA synthesis, but the dynamic mechanism of the T4 td group I intron during circularization remains unclear. Now, cryo-EM structures of both the linear and circular forms of the T4 td intron are solved, revealing key conformational shifts essential for RNA circularization.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 12","pages":"1281-1294"},"PeriodicalIF":44.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536471","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}
Pub Date : 2025-11-18DOI: 10.1038/s41929-025-01449-9
Thomas Götsch, Daniel Cruz, Patrick Zeller, Anna Rabe, Maik Dreyer, Nicolas Cosanne, Frank Girgsdies, Jasmin Allan, Michael Hävecker, Anna Efimenko, Mihaela Gorgoi, Sharif Najafishirtari, Malte Behrens, Robert Schlögl, Axel Knop-Gericke, Thomas Lunkenbein
Transition metal oxides are excellent catalysts for selective oxidation reactions, which are a prominent source of industrially relevant chemicals. However, these reactions suffer from multiple competing reaction pathways, limiting the selectivity. Thus, it is essential to gain an understanding of the underlying processes occurring on the catalyst that affect its performance. Here we synergistically combine operando X-ray spectroscopy and operando transmission electron microscopy to unravel a network of solid-state processes that controls the catalytic properties of Co3O4 in the oxidation of 2-propanol towards acetone. These include exsolution, diffusion and defect formation, which strongly distort the catalyst lattice at lower temperatures. Ultimately, they also lead to a maximum in acetone selectivity when the catalyst is trapped in a frustrated or metastable state at the onset of crystallization of the exsolved particles to CoO and void formation, which coincides with the maximum in surface cobalt oxidation state in the spinel. The notion that catalysts are static entities that barely change under operation is still prevalent although it is often not true. Here, a range of operando and in situ techniques reveals the dynamic nature of Co3O4 during the oxidation of 2-propanol to acetone, unveiling a network of interconnected solid-state processes, such as exsolution, diffusion or void formation, that govern the catalytic performance.
{"title":"Local solid-state processes adjust the selectivity in catalytic oxidation reactions on cobalt oxides","authors":"Thomas Götsch, Daniel Cruz, Patrick Zeller, Anna Rabe, Maik Dreyer, Nicolas Cosanne, Frank Girgsdies, Jasmin Allan, Michael Hävecker, Anna Efimenko, Mihaela Gorgoi, Sharif Najafishirtari, Malte Behrens, Robert Schlögl, Axel Knop-Gericke, Thomas Lunkenbein","doi":"10.1038/s41929-025-01449-9","DOIUrl":"10.1038/s41929-025-01449-9","url":null,"abstract":"Transition metal oxides are excellent catalysts for selective oxidation reactions, which are a prominent source of industrially relevant chemicals. However, these reactions suffer from multiple competing reaction pathways, limiting the selectivity. Thus, it is essential to gain an understanding of the underlying processes occurring on the catalyst that affect its performance. Here we synergistically combine operando X-ray spectroscopy and operando transmission electron microscopy to unravel a network of solid-state processes that controls the catalytic properties of Co3O4 in the oxidation of 2-propanol towards acetone. These include exsolution, diffusion and defect formation, which strongly distort the catalyst lattice at lower temperatures. Ultimately, they also lead to a maximum in acetone selectivity when the catalyst is trapped in a frustrated or metastable state at the onset of crystallization of the exsolved particles to CoO and void formation, which coincides with the maximum in surface cobalt oxidation state in the spinel. The notion that catalysts are static entities that barely change under operation is still prevalent although it is often not true. Here, a range of operando and in situ techniques reveals the dynamic nature of Co3O4 during the oxidation of 2-propanol to acetone, unveiling a network of interconnected solid-state processes, such as exsolution, diffusion or void formation, that govern the catalytic performance.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 12","pages":"1314-1324"},"PeriodicalIF":44.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41929-025-01449-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Substituted cyclohexanes are ubiquitous motifs in bioactive molecules. Thermodynamically disfavoured substituted cyclohexane scaffolds can significantly enhance both the biological activity and pharmacokinetic properties of potential drugs. However, achieving stereoselective cross-coupling for the synthesis of these structures with precise kinetic control remains a challenge. Here we present a modular reductive cross-coupling reaction that enables the stereoselective synthesis of thermodynamically disfavoured substituted cyclohexanes, employing simple alkenes as coupling partners. Mechanistically, the exceptional stereochemistry of this reaction is governed by a Heck-type migratory insertion step. The utility of this method is also demonstrated through the concise synthesis of bioactive molecules. Thermodynamically disfavoured substituted cyclohexane compounds often display superior physical and bioactive properties to their isomeric counterparts. Now their synthesis is achieved by Ni-catalysed coupling of substituted methylenecyclohexanes with electrophiles under kinetic control.
{"title":"A stereoselective reductive cross-coupling reaction with kinetic control","authors":"Zhenpeng Shen, Hongjin Shi, Yangyang Li, Xiangyu Zhang, Xiaotian Qi, Guoyin Yin","doi":"10.1038/s41929-025-01440-4","DOIUrl":"10.1038/s41929-025-01440-4","url":null,"abstract":"Substituted cyclohexanes are ubiquitous motifs in bioactive molecules. Thermodynamically disfavoured substituted cyclohexane scaffolds can significantly enhance both the biological activity and pharmacokinetic properties of potential drugs. However, achieving stereoselective cross-coupling for the synthesis of these structures with precise kinetic control remains a challenge. Here we present a modular reductive cross-coupling reaction that enables the stereoselective synthesis of thermodynamically disfavoured substituted cyclohexanes, employing simple alkenes as coupling partners. Mechanistically, the exceptional stereochemistry of this reaction is governed by a Heck-type migratory insertion step. The utility of this method is also demonstrated through the concise synthesis of bioactive molecules. Thermodynamically disfavoured substituted cyclohexane compounds often display superior physical and bioactive properties to their isomeric counterparts. Now their synthesis is achieved by Ni-catalysed coupling of substituted methylenecyclohexanes with electrophiles under kinetic control.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 11","pages":"1241-1249"},"PeriodicalIF":44.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455582","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}
Pub Date : 2025-11-05DOI: 10.1038/s41929-025-01430-6
Negin Orouji, Jeffrey A. Bennett, Richard B. Canty, Long Qi, Shijing Sun, Paulami Majumdar, Chong Liu, Núria López, Neil M. Schweitzer, John R. Kitchin, Hongliang Xin, Milad Abolhasani
Catalysis is essential to modern chemical manufacturing and environmental sustainability. Yet, traditional catalyst discovery remains slow, resource-intensive and constrained by human-centred trial-and-error workflows. The integration of artificial intelligence (AI), robotics and high-throughput experimentation into self-driving laboratories (SDLs) presents a transformative approach for accelerating catalyst discovery and optimization. SDLs combine automated synthesis and testing platforms, data infrastructures and AI-guided decision-making to enable information-rich experimentation and the fast-tracked generation of scientific knowledge. However, in our view, realizing the full potential of SDLs requires sustained human oversight to ensure rigorous data curation, validate machine-generated hypotheses and establish benchmarks to mitigate AI-related errors. This Perspective outlines core SDL components, including hardware, computational modelling and AI-guided decision-making. We discuss challenges in data availability, integration of computational and experimental workflows and scalable platforms. Finally, we outline immediate opportunities to broaden the adoption of autonomous experimentation in catalysis. The rise of artificial intelligence together with advances in robotics is leading a surge of interest in self-driving laboratories. This Perspective discusses self-driving laboratories for catalysis while arguing that, to achieve their full potential, human oversight is required.
{"title":"Autonomous catalysis research with human–AI–robot collaboration","authors":"Negin Orouji, Jeffrey A. Bennett, Richard B. Canty, Long Qi, Shijing Sun, Paulami Majumdar, Chong Liu, Núria López, Neil M. Schweitzer, John R. Kitchin, Hongliang Xin, Milad Abolhasani","doi":"10.1038/s41929-025-01430-6","DOIUrl":"10.1038/s41929-025-01430-6","url":null,"abstract":"Catalysis is essential to modern chemical manufacturing and environmental sustainability. Yet, traditional catalyst discovery remains slow, resource-intensive and constrained by human-centred trial-and-error workflows. The integration of artificial intelligence (AI), robotics and high-throughput experimentation into self-driving laboratories (SDLs) presents a transformative approach for accelerating catalyst discovery and optimization. SDLs combine automated synthesis and testing platforms, data infrastructures and AI-guided decision-making to enable information-rich experimentation and the fast-tracked generation of scientific knowledge. However, in our view, realizing the full potential of SDLs requires sustained human oversight to ensure rigorous data curation, validate machine-generated hypotheses and establish benchmarks to mitigate AI-related errors. This Perspective outlines core SDL components, including hardware, computational modelling and AI-guided decision-making. We discuss challenges in data availability, integration of computational and experimental workflows and scalable platforms. Finally, we outline immediate opportunities to broaden the adoption of autonomous experimentation in catalysis. The rise of artificial intelligence together with advances in robotics is leading a surge of interest in self-driving laboratories. This Perspective discusses self-driving laboratories for catalysis while arguing that, to achieve their full potential, human oversight is required.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 11","pages":"1135-1145"},"PeriodicalIF":44.6,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145441152","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}
Pub Date : 2025-11-03DOI: 10.1038/s41929-025-01436-0
Zhi Zou, Indrek Kalvet, Boris Lozhkin, Elinor Morris, Kailin Zhang, Dongping Chen, Marco L. Ernst, Xiang Zhang, David Baker, Thomas R. Ward
Artificial metalloenzymes present a promising avenue for abiotic catalysis within living systems. However, their in vivo application is currently limited by critical challenges, particularly in selecting suitable protein scaffolds capable of binding abiotic cofactors and maintaining catalytic activity in complex media. Here we address these limitations by introducing an artificial metathase—an artificial metalloenzyme designed for ring-closing metathesis—for whole-cell biocatalysis. Our approach integrates a tailored metal cofactor into a hyper-stable, de novo-designed protein. By combining computational design with genetic optimization, a binding affinity (KD ≤ 0.2 μM) between the protein scaffold and cofactor is achieved through supramolecular anchoring. Directed evolution of the artificial metathase yielded variants exhibiting excellent catalytic performance (turnover number ≥1,000) and biocompatibility. This work represents a pronounced leap in the de novo design and in cellulo engineering of artificial metalloenzymes, paving the way for abiological catalysis in living systems. The creation of artificial metalloenzymes compatible with complex biological settings could enable broad applications. Now a de novo-designed artificial metalloenzyme containing an abiological ruthenium cofactor is reported and optimized for ring-closing metathesis in the cytoplasm of whole cells.
{"title":"De novo design and evolution of an artificial metathase for cytoplasmic olefin metathesis","authors":"Zhi Zou, Indrek Kalvet, Boris Lozhkin, Elinor Morris, Kailin Zhang, Dongping Chen, Marco L. Ernst, Xiang Zhang, David Baker, Thomas R. Ward","doi":"10.1038/s41929-025-01436-0","DOIUrl":"10.1038/s41929-025-01436-0","url":null,"abstract":"Artificial metalloenzymes present a promising avenue for abiotic catalysis within living systems. However, their in vivo application is currently limited by critical challenges, particularly in selecting suitable protein scaffolds capable of binding abiotic cofactors and maintaining catalytic activity in complex media. Here we address these limitations by introducing an artificial metathase—an artificial metalloenzyme designed for ring-closing metathesis—for whole-cell biocatalysis. Our approach integrates a tailored metal cofactor into a hyper-stable, de novo-designed protein. By combining computational design with genetic optimization, a binding affinity (KD ≤ 0.2 μM) between the protein scaffold and cofactor is achieved through supramolecular anchoring. Directed evolution of the artificial metathase yielded variants exhibiting excellent catalytic performance (turnover number ≥1,000) and biocompatibility. This work represents a pronounced leap in the de novo design and in cellulo engineering of artificial metalloenzymes, paving the way for abiological catalysis in living systems. The creation of artificial metalloenzymes compatible with complex biological settings could enable broad applications. Now a de novo-designed artificial metalloenzyme containing an abiological ruthenium cofactor is reported and optimized for ring-closing metathesis in the cytoplasm of whole cells.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 11","pages":"1208-1219"},"PeriodicalIF":44.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41929-025-01436-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radical repositioning, a transformative strategy for activating remote C–C/C–H bonds through the relocation of unpaired electrons, remains unexplored in biological systems. Recent advances in photogenerated nitrogen-centred radicals (NCRs) have enabled radical 1,2- to 1,n-translocations for organic synthesis, but achieving stereochemical control over the repositioned prochiral radicals is challenging. Here we introduce a visible light-promoted, thiamine-dependent radical biocatalytic system that leverages NCR-triggered radical repositioning for the enantioselective acylation of remote C–C/C–H bonds. Synergistic single-electron transfer and thiamine cofactor-mediated biocatalysis enables the generation of NCRs, which translocate to remote carbon-centred radicals via 1,n-hydrogen atom transfer or C–C fragmentation, and facilitates the subsequent radical cross-coupling within the active site, producing diverse chiral nitriles and amides with a remote carbonyl group (43 examples with a δ-, ε-, ζ- or η-position relative to the N atom) in good-to-excellent enantiomeric ratios (up to 99.5:0.5). This strategy couples radical repositioning and enzymes to unlock the selective functionalization of remote C–H/C–C bonds. Radical repositioning to activate remote bonds is underdeveloped in synthetic biocatalysis. Now a photobiocatalytic system couples light-driven single-electron transfer and the relocation of unpaired electrons to activate remote C–C and C–H bonds for enzymatically controlled enantioselective acylation.
{"title":"Photobiocatalytic radical repositioning for enantioselective acylation of remote C–C/C–H bonds","authors":"Yang Ming, Zhouping Wu, Yuanyuan Xu, Yao Chen, Zhongqiu Xing, Xichao Peng, Jianlin Chun, Hailong Sun, Jiayu Wu, Yu Zheng, Ling Jiang, Xiaoqiang Huang","doi":"10.1038/s41929-025-01435-1","DOIUrl":"10.1038/s41929-025-01435-1","url":null,"abstract":"Radical repositioning, a transformative strategy for activating remote C–C/C–H bonds through the relocation of unpaired electrons, remains unexplored in biological systems. Recent advances in photogenerated nitrogen-centred radicals (NCRs) have enabled radical 1,2- to 1,n-translocations for organic synthesis, but achieving stereochemical control over the repositioned prochiral radicals is challenging. Here we introduce a visible light-promoted, thiamine-dependent radical biocatalytic system that leverages NCR-triggered radical repositioning for the enantioselective acylation of remote C–C/C–H bonds. Synergistic single-electron transfer and thiamine cofactor-mediated biocatalysis enables the generation of NCRs, which translocate to remote carbon-centred radicals via 1,n-hydrogen atom transfer or C–C fragmentation, and facilitates the subsequent radical cross-coupling within the active site, producing diverse chiral nitriles and amides with a remote carbonyl group (43 examples with a δ-, ε-, ζ- or η-position relative to the N atom) in good-to-excellent enantiomeric ratios (up to 99.5:0.5). This strategy couples radical repositioning and enzymes to unlock the selective functionalization of remote C–H/C–C bonds. Radical repositioning to activate remote bonds is underdeveloped in synthetic biocatalysis. Now a photobiocatalytic system couples light-driven single-electron transfer and the relocation of unpaired electrons to activate remote C–C and C–H bonds for enzymatically controlled enantioselective acylation.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 11","pages":"1198-1207"},"PeriodicalIF":44.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427398","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}
Pub Date : 2025-10-31DOI: 10.1038/s41929-025-01438-y
Shengyang Ni, Alexios Stamoulis, Vanessa A. Béland, Josep Cornella
The Heck reaction, which is widely used for the construction of C‒C bonds, is a cornerstone of modern organic synthesis. Traditionally, this transformation relies on transition metal catalysts, whose frontier d-orbitals cement the mechanism and scope of the reaction. Here we present a conceptually distinct Heck-type coupling strategy that replaces transition metals with a photoactive bismuth complex, marking an advance in main group catalysis. This approach leverages the distinctive electronic and photophysical properties of bismuth, providing a reimagined reaction pathway. The bismuth catalyst undergoes a photo-induced ligand-to-metal charge transfer processes, unmasking a Bi(II) species capable of halogen atom transfer (XAT) processes with alkyl iodides. The multifaceted redox-dependent photophysical properties of the bismuth catalyst facilitate the coupling of aryl and alkyl electrophiles with styrenes through an intricate interplay of mechanistic steps. The method provides a mechanistic blueprint for accessing coveted Bi(II) species, offering an alternative to transition metal catalysis in organic synthesis. The Heck reaction is widely used in modern organic chemistry. Here the authors provide an alternative approach to common transition-metal catalysis, leveraging access to Bi(II) species thanks to bismuth’s photophysical properties.
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