Pub Date : 2024-10-23DOI: 10.1038/s41929-024-01237-x
Milena L. Czyz, Tyra H. Horngren, Andrew J. Kondopoulos, Liam J. Franov, José A. Forni, Le Nhan Pham, Michelle L. Coote, Anastasios Polyzos
Organometallic reagents are routinely used as fundamental building blocks in organic chemistry to rapidly diversify molecular fragments via carbanion intermediates. However, the catalytic generation of carbanion equivalents, particularly from sp3-hybridized alkyl scaffolds, remains an underdeveloped goal in chemical synthesis. Here we disclose an approach for the generation of alkyl carbanions via single-electron reduction of aryl alkenes, enabled by multi-photon photoredox catalysis. We demonstrate that photocatalytically induced alkyl carbanions engage in intermolecular C–C bond-forming reactions with carbonyl electrophiles. Central to this method is the controlled formation of an alkene distonic radical anion intermediate that undergoes nucleophilic addition, followed by a kinetically favoured reductive polar crossover to produce a second carbanion available for further diversification. The versatility of this protocol was illustrated by the development of four distinct intermolecular C–C bond-forming reactions with aromatic alkenes (hydroalkoxylation, hydroamidation, aminoalkylation and carboxyaminoalkylation) to generate a range of valuable and complex scaffolds.
{"title":"Photocatalytic generation of alkyl carbanions from aryl alkenes","authors":"Milena L. Czyz, Tyra H. Horngren, Andrew J. Kondopoulos, Liam J. Franov, José A. Forni, Le Nhan Pham, Michelle L. Coote, Anastasios Polyzos","doi":"10.1038/s41929-024-01237-x","DOIUrl":"https://doi.org/10.1038/s41929-024-01237-x","url":null,"abstract":"<p>Organometallic reagents are routinely used as fundamental building blocks in organic chemistry to rapidly diversify molecular fragments via carbanion intermediates. However, the catalytic generation of carbanion equivalents, particularly from <i>sp</i><sup>3</sup>-hybridized alkyl scaffolds, remains an underdeveloped goal in chemical synthesis. Here we disclose an approach for the generation of alkyl carbanions via single-electron reduction of aryl alkenes, enabled by multi-photon photoredox catalysis. We demonstrate that photocatalytically induced alkyl carbanions engage in intermolecular C–C bond-forming reactions with carbonyl electrophiles. Central to this method is the controlled formation of an alkene distonic radical anion intermediate that undergoes nucleophilic addition, followed by a kinetically favoured reductive polar crossover to produce a second carbanion available for further diversification. The versatility of this protocol was illustrated by the development of four distinct intermolecular C–C bond-forming reactions with aromatic alkenes (hydroalkoxylation, hydroamidation, aminoalkylation and carboxyaminoalkylation) to generate a range of valuable and complex scaffolds.</p><figure></figure>","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"67 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487134","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 : 2024-10-22DOI: 10.1038/s41929-024-01239-9
Chetan C. Chintawar, Ranjini Laskar, Debanjan Rana, Felix Schäfer, Nele Van Wyngaerden, Subhabrata Dutta, Constantin G. Daniliuc, Frank Glorius
Replacing planar aromatic rings in drug molecules with C(sp3)-rich isosteric mimetics, such as bicyclo[n.1.1]alkanes, can significantly alter their physicochemical and pharmacokinetic properties, often leading to higher clinical success rates. However, unlike a benzene ring, the structurally rigid C(sp3)-rich isosteric mimetics of heteroaromatic rings are rare. Heterobicyclo[n.1.1]alkanes are promising in this regard, but the lack of modular synthetic methods has currently hindered their exploration. We envisioned that the strategic and selective insertion of different heteroatomic units to bicyclo[1.1.0]butanes could offer a highly modular platform to access diverse heterobicyclo[n.1.1]alkanes. Herein we report a photoredox-catalysed highly regioselective and chemoselective insertion of amidyl radicals to bicyclo[1.1.0]butanes, providing direct access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes. The exit vector analysis shows a geometric resemblance of these C(sp3)-rich heterobicyclic motifs with pyridine and pyrimidine derivatives, suggesting their potential as isosteric mimetics of such medicinally important heterocycles. Additionally, various downstream transformations demonstrate their utility as versatile building blocks in synthetic chemistry. Heteroatom-substituted C(sp3)-rich polycyclic hydrocarbon rings, isosteric to heterocyclic rings, are not common due to the challenging synthesis. Now a photoredox-catalysed strategy to insert amidyl radicals into bicyclo[1.1.0]butanes is presented, providing direct access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes.
{"title":"Photoredox-catalysed amidyl radical insertion to bicyclo[1.1.0]butanes","authors":"Chetan C. Chintawar, Ranjini Laskar, Debanjan Rana, Felix Schäfer, Nele Van Wyngaerden, Subhabrata Dutta, Constantin G. Daniliuc, Frank Glorius","doi":"10.1038/s41929-024-01239-9","DOIUrl":"10.1038/s41929-024-01239-9","url":null,"abstract":"Replacing planar aromatic rings in drug molecules with C(sp3)-rich isosteric mimetics, such as bicyclo[n.1.1]alkanes, can significantly alter their physicochemical and pharmacokinetic properties, often leading to higher clinical success rates. However, unlike a benzene ring, the structurally rigid C(sp3)-rich isosteric mimetics of heteroaromatic rings are rare. Heterobicyclo[n.1.1]alkanes are promising in this regard, but the lack of modular synthetic methods has currently hindered their exploration. We envisioned that the strategic and selective insertion of different heteroatomic units to bicyclo[1.1.0]butanes could offer a highly modular platform to access diverse heterobicyclo[n.1.1]alkanes. Herein we report a photoredox-catalysed highly regioselective and chemoselective insertion of amidyl radicals to bicyclo[1.1.0]butanes, providing direct access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes. The exit vector analysis shows a geometric resemblance of these C(sp3)-rich heterobicyclic motifs with pyridine and pyrimidine derivatives, suggesting their potential as isosteric mimetics of such medicinally important heterocycles. Additionally, various downstream transformations demonstrate their utility as versatile building blocks in synthetic chemistry. Heteroatom-substituted C(sp3)-rich polycyclic hydrocarbon rings, isosteric to heterocyclic rings, are not common due to the challenging synthesis. Now a photoredox-catalysed strategy to insert amidyl radicals into bicyclo[1.1.0]butanes is presented, providing direct access to 2-oxa-4-azabicyclo[3.1.1]hept-3-enes.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1232-1242"},"PeriodicalIF":42.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41929-024-01239-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452580","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}
Pub Date : 2024-10-17DOI: 10.1038/s41929-024-01234-0
Benjamin J. S. Rowsell, Harry M. O’Brien, Gayathri Athavan, Patrick R. Daley-Dee, Johannes Krieger, Emma Richards, Karl Heaton, Ian J. S. Fairlamb, Robin B. Bedford
The very widely exploited Suzuki biaryl coupling reaction typically requires catalysts based on palladium, but there is an increasing desire to replace this metal with a more sustainable, less expensive alternative, with catalysts based on iron being a particularly attractive target. Here we show that a simple iron-based catalyst with an N-heterocyclic carbene ligand can be used to excellent effect in the Suzuki biaryl coupling of aryl chloride substrates with aryl boronic esters activated by an organolithium reagent. Mechanistic studies suggest the possible involvement of Fe(I) as the lowest oxidation state on the catalytic manifold and show that the challenging step is not activation of the aryl chloride substrate, but rather the transmetallation step. These findings are likely to lead to a renaissance of iron-catalysed carbon–carbon bond-forming transformations with soft nucleophilic coupling partners. The replacement of palladium with other metal catalysts in C–C bond-forming reactions is attractive in terms of costs and sustainability. Now an iron-based catalyst is successfully employed in the Suzuki cross-coupling of aryl chlorides with aryl boronic esters activated with tert-butyl lithium.
{"title":"The iron-catalysed Suzuki coupling of aryl chlorides","authors":"Benjamin J. S. Rowsell, Harry M. O’Brien, Gayathri Athavan, Patrick R. Daley-Dee, Johannes Krieger, Emma Richards, Karl Heaton, Ian J. S. Fairlamb, Robin B. Bedford","doi":"10.1038/s41929-024-01234-0","DOIUrl":"10.1038/s41929-024-01234-0","url":null,"abstract":"The very widely exploited Suzuki biaryl coupling reaction typically requires catalysts based on palladium, but there is an increasing desire to replace this metal with a more sustainable, less expensive alternative, with catalysts based on iron being a particularly attractive target. Here we show that a simple iron-based catalyst with an N-heterocyclic carbene ligand can be used to excellent effect in the Suzuki biaryl coupling of aryl chloride substrates with aryl boronic esters activated by an organolithium reagent. Mechanistic studies suggest the possible involvement of Fe(I) as the lowest oxidation state on the catalytic manifold and show that the challenging step is not activation of the aryl chloride substrate, but rather the transmetallation step. These findings are likely to lead to a renaissance of iron-catalysed carbon–carbon bond-forming transformations with soft nucleophilic coupling partners. The replacement of palladium with other metal catalysts in C–C bond-forming reactions is attractive in terms of costs and sustainability. Now an iron-based catalyst is successfully employed in the Suzuki cross-coupling of aryl chlorides with aryl boronic esters activated with tert-butyl lithium.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1186-1198"},"PeriodicalIF":42.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41929-024-01234-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440846","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}
Pub Date : 2024-10-14DOI: 10.1038/s41929-024-01236-y
Seongmin Jin, Choah Kwon, Aram Bugaev, Bartu Karakurt, Yu-Cheng Lin, Louisa Savereide, Liping Zhong, Victor Boureau, Olga Safonova, Sangtae Kim, Jeremy S. Luterbacher
The difficulty of synthesizing uniform atomically precise active sites limits our ability to engineer increasingly more active heterogeneous catalysts for the hydrogenation of CO2 to methanol. Here we design Cu/ZrOx clusters on MgO with near atomic precision for CO2 hydrogenation using a liquid-phase atomic layer deposition method. The controlled cluster structure modulates the binding strength of CO2 and moderately stabilizes monodentate formate—an essential reaction intermediate for methanol production. We achieved a methanol selectivity of 100 and 76.7% at 200 and 250 °C, respectively and a methanol productivity that was one to two orders of magnitude higher than when the same catalysts were prepared by impregnation. Ab initio computations show that Cu/ZrOx clusters can tune the oxidation of Zr, which controls the stability of reaction intermediates on the catalyst. Our approach demonstrates the potential of precise atomic control of catalytic clusters to improve catalytic productivity. Achieving atomic control during the synthesis of heterogeneous catalysts remains challenging. Here the authors tackle this challenge by applying a liquid-phase atomic layer deposition approach to the synthesis of Cu/ZrOx clusters on MgO as efficient catalysts for CO2 hydrogenation to methanol.
由于难以合成原子精度一致的活性位点，限制了我们设计活性越来越高的异质催化剂将二氧化碳氢化为甲醇的能力。在这里，我们采用液相原子层沉积方法，在氧化镁上设计了接近原子精度的铜/氧化锆团簇，用于二氧化碳加氢。可控的团簇结构调节了 CO2 的结合强度，并适度稳定了单齿形式--甲醇生产的重要反应中间体。在 200 ℃ 和 250 ℃ 条件下，我们分别获得了 100% 和 76.7% 的甲醇选择性，甲醇生产率比通过浸渍法制备的相同催化剂高出一到两个数量级。Ab initio 计算表明，Cu/ZrOx 团簇可以调节 Zr 的氧化，从而控制催化剂上反应中间产物的稳定性。我们的方法证明了对催化剂团簇进行精确原子控制以提高催化生产率的潜力。
{"title":"Atom-by-atom design of Cu/ZrOx clusters on MgO for CO2 hydrogenation using liquid-phase atomic layer deposition","authors":"Seongmin Jin, Choah Kwon, Aram Bugaev, Bartu Karakurt, Yu-Cheng Lin, Louisa Savereide, Liping Zhong, Victor Boureau, Olga Safonova, Sangtae Kim, Jeremy S. Luterbacher","doi":"10.1038/s41929-024-01236-y","DOIUrl":"10.1038/s41929-024-01236-y","url":null,"abstract":"The difficulty of synthesizing uniform atomically precise active sites limits our ability to engineer increasingly more active heterogeneous catalysts for the hydrogenation of CO2 to methanol. Here we design Cu/ZrOx clusters on MgO with near atomic precision for CO2 hydrogenation using a liquid-phase atomic layer deposition method. The controlled cluster structure modulates the binding strength of CO2 and moderately stabilizes monodentate formate—an essential reaction intermediate for methanol production. We achieved a methanol selectivity of 100 and 76.7% at 200 and 250 °C, respectively and a methanol productivity that was one to two orders of magnitude higher than when the same catalysts were prepared by impregnation. Ab initio computations show that Cu/ZrOx clusters can tune the oxidation of Zr, which controls the stability of reaction intermediates on the catalyst. Our approach demonstrates the potential of precise atomic control of catalytic clusters to improve catalytic productivity. Achieving atomic control during the synthesis of heterogeneous catalysts remains challenging. Here the authors tackle this challenge by applying a liquid-phase atomic layer deposition approach to the synthesis of Cu/ZrOx clusters on MgO as efficient catalysts for CO2 hydrogenation to methanol.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1199-1212"},"PeriodicalIF":42.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430570","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 : 2024-10-10DOI: 10.1038/s41929-024-01231-3
Filippo Buttignol, Jörg W. A. Fischer, Adam H. Clark, Martin Elsener, Alberto Garbujo, Pierdomenico Biasi, Izabela Czekaj, Maarten Nachtegaal, Gunnar Jeschke, Oliver Kröcher, Davide Ferri
Iron-exchanged zeolites are often deployed industrially to remediate nitric oxide (NO) and nitrous oxide (N2O) emissions. The nature of the active site and the reaction mechanism involved in the simultaneous removal of NO and N2O remain largely unknown, primarily because of the heterogeneity of Fe species. Here we combined catalytic experiments with transient operando X-ray absorption spectroscopy, electron paramagnetic resonance and diffuse reflectance infrared Fourier transform spectroscopy to disentangle the nature of Fe species and elementary reaction steps. We identified spectroscopically the square-planar Fe2+ sites in the β-cationic position responsible for N2O activation and the related redox cycle. These sites communicate with tetrahedrally coordinated Fe2+ sites in the adjacent γ-cationic position, accounting for adsorption and redox-mediated oxidation of NO. The availability of NH3 adsorbed on neighbouring Brønsted acid sites regulates the overall reaction rate of this dual-site mechanism by intercepting the NO oxidation sequence. The cooperation between these redox processes ensures enhanced conversion of both NO and N2O.
工业上经常使用铁交换沸石来清除一氧化氮（NO）和一氧化二氮（N2O）的排放。同时去除 NO 和 N2O 所涉及的活性位点性质和反应机理在很大程度上仍不为人所知，这主要是因为铁的种类具有异质性。在此，我们将催化实验与瞬态操作 X 射线吸收光谱、电子顺磁共振和漫反射红外傅立叶变换光谱相结合，以厘清铁物种的性质和基本反应步骤。我们从光谱学角度确定了位于 β 阳离子位置的方形平面 Fe2+ 位点，这些位点负责 N2O 活化和相关的氧化还原循环。这些位点与相邻 γ 阳离子位点上的四面体配位 Fe2+ 位点相通，从而实现了 NO 的吸附和氧化还原。相邻布氏酸位点上吸附的 NH3 可通过截断 NO 氧化顺序来调节这种双位点机制的总体反应速率。这些氧化还原过程之间的合作确保了 NO 和 N2O 转化率的提高。
{"title":"Iron-catalysed cooperative redox mechanism for the simultaneous conversion of nitrous oxide and nitric oxide","authors":"Filippo Buttignol, Jörg W. A. Fischer, Adam H. Clark, Martin Elsener, Alberto Garbujo, Pierdomenico Biasi, Izabela Czekaj, Maarten Nachtegaal, Gunnar Jeschke, Oliver Kröcher, Davide Ferri","doi":"10.1038/s41929-024-01231-3","DOIUrl":"https://doi.org/10.1038/s41929-024-01231-3","url":null,"abstract":"<p>Iron-exchanged zeolites are often deployed industrially to remediate nitric oxide (NO) and nitrous oxide (N<sub>2</sub>O) emissions. The nature of the active site and the reaction mechanism involved in the simultaneous removal of NO and N<sub>2</sub>O remain largely unknown, primarily because of the heterogeneity of Fe species. Here we combined catalytic experiments with transient operando X-ray absorption spectroscopy, electron paramagnetic resonance and diffuse reflectance infrared Fourier transform spectroscopy to disentangle the nature of Fe species and elementary reaction steps. We identified spectroscopically the square-planar Fe<sup>2+</sup> sites in the β-cationic position responsible for N<sub>2</sub>O activation and the related redox cycle. These sites communicate with tetrahedrally coordinated Fe<sup>2+</sup> sites in the adjacent γ-cationic position, accounting for adsorption and redox-mediated oxidation of NO. The availability of NH<sub>3</sub> adsorbed on neighbouring Brønsted acid sites regulates the overall reaction rate of this dual-site mechanism by intercepting the NO oxidation sequence. The cooperation between these redox processes ensures enhanced conversion of both NO and N<sub>2</sub>O.</p><figure></figure>","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"2 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398246","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 : 2024-10-03DOI: 10.1038/s41929-024-01230-4
Tianran Deng, Xiang-Lei Han, Yang Yu, Cheng Cheng, Xiangyuan Liu, Yuhong Gao, Keqiang Wu, Zhenghua Li, Jisheng Luo, Li Deng
Catalytic enantioselective α-C–H functionalization of widely available achiral alkyl amines could provide an ideal synthetic approach towards chiral amines. However, the inert nature of the α-C–H of alkyl amines renders their activation as carbanionic nucleophiles for catalytic asymmetric reactions an important yet unmet challenge. Here we describe how N-arylidene-protected alkyl amines could be activated as carbanions for asymmetric conjugate addition and the Mannich reaction. These results represent an intriguing and generally useful approach to the synthesis of chiral α,α-dialkyl amines. More importantly, they highlight the enormous potential of N-arylidene-protected amines as readily available and widely applicable synthons for the asymmetric synthesis of chiral amines. The catalytic activation of alkyl amines as α-nitrogen carbanions is challenging. Now the activation of N-arylidene-protected alkyl amines as carbanions by chiral ammonium organocatalysis for asymmetric conjugate addition and the Mannich reaction is reported, affording chiral α,α-dialkyl amines.
{"title":"Organocatalytic asymmetric α-C–H functionalization of alkyl amines","authors":"Tianran Deng, Xiang-Lei Han, Yang Yu, Cheng Cheng, Xiangyuan Liu, Yuhong Gao, Keqiang Wu, Zhenghua Li, Jisheng Luo, Li Deng","doi":"10.1038/s41929-024-01230-4","DOIUrl":"10.1038/s41929-024-01230-4","url":null,"abstract":"Catalytic enantioselective α-C–H functionalization of widely available achiral alkyl amines could provide an ideal synthetic approach towards chiral amines. However, the inert nature of the α-C–H of alkyl amines renders their activation as carbanionic nucleophiles for catalytic asymmetric reactions an important yet unmet challenge. Here we describe how N-arylidene-protected alkyl amines could be activated as carbanions for asymmetric conjugate addition and the Mannich reaction. These results represent an intriguing and generally useful approach to the synthesis of chiral α,α-dialkyl amines. More importantly, they highlight the enormous potential of N-arylidene-protected amines as readily available and widely applicable synthons for the asymmetric synthesis of chiral amines. The catalytic activation of alkyl amines as α-nitrogen carbanions is challenging. Now the activation of N-arylidene-protected alkyl amines as carbanions by chiral ammonium organocatalysis for asymmetric conjugate addition and the Mannich reaction is reported, affording chiral α,α-dialkyl amines.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 10","pages":"1076-1085"},"PeriodicalIF":42.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368994","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 : 2024-10-03DOI: 10.1038/s41929-024-01240-2
Donato Decarolis, Monik Panchal, Matthew Quesne, Khaled Mohammed, Shaojun Xu, Mark Isaacs, Adam H. Clark, Luke L. Keenan, Takuo Wakisaka, Kohei Kusada, Hiroshi Kitagawa, C. Richard A. Catlow, Emma K. Gibson, Alexandre Goguet, Peter P. Wells
{"title":"Author Correction: Localized thermal levering events drive spontaneous kinetic oscillations during CO oxidation on Rh/Al2O3","authors":"Donato Decarolis, Monik Panchal, Matthew Quesne, Khaled Mohammed, Shaojun Xu, Mark Isaacs, Adam H. Clark, Luke L. Keenan, Takuo Wakisaka, Kohei Kusada, Hiroshi Kitagawa, C. Richard A. Catlow, Emma K. Gibson, Alexandre Goguet, Peter P. Wells","doi":"10.1038/s41929-024-01240-2","DOIUrl":"10.1038/s41929-024-01240-2","url":null,"abstract":"","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1243-1243"},"PeriodicalIF":42.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41929-024-01240-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368993","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}
Pub Date : 2024-10-01DOI: 10.1038/s41929-024-01233-1
Victoria A. Maola, Eric J. Yik, Mohammad Hajjar, Joy J. Lee, Manuel J. Holguin, Riley N. Quijano, Kalvin K. Nguyen, Katherine L. Ho, Jenny V. Medina, Nicholas Chim, John C. Chaput
Reprogramming DNA polymerases to synthesize xeno-nucleic acids (XNAs) is an important challenge that tests current enzyme engineering tools. Here we describe an evolutionary campaign aimed at generating an XNA polymerase that can efficiently make α-l-threofuranosyl nucleic acid (TNA)—an artificial genetic polymer that is recalcitrant to nucleases and resistant to acid-mediated degradation. Starting from a homologous recombination library, iterative cycles of selection were performed to traverse the fitness landscape in search of neutral mutations with increased evolutionary potential. Subsequent directed evolution of focused mutagenic libraries yielded 10–92, a newly engineered TNA polymerase that functions with a catalytic rate of ∼1 nt s−1 and >99% fidelity. A crystal structure of the closed ternary complex reveals the degree of structural change required to remodel the active site pocket for improved TNA synthesis activity. Together, these data demonstrate the importance of recombination as a strategy for evolving XNA polymerases with considerable practical value for biotechnology and medicine. The catalytic power of DNA polymerases for artificial genetic polymer (XNA) synthesis remains underdeveloped. Now, the evolution and structure of an α-l-threofuranosyl nucleic acid polymerase is described that achieves XNA synthesis with ∼1 nt s−1 and >99% template-copying fidelity.
重新编程 DNA 聚合酶以合成异种核酸（XNA）是一项重要挑战，对现有的酶工程工具提出了考验。在这里，我们描述了一项旨在产生一种XNA聚合酶的进化活动，这种聚合酶可以有效地制造α-l-苏呋糖核酸（TNA）--一种对核酸酶有抵抗力、对酸介导的降解有抵抗力的人工基因聚合物。从同源重组文库开始，迭代选择循环遍历适合度景观，寻找具有更大进化潜力的中性突变。随后的定向进化聚焦诱变文库产生了 10-92，这是一种新设计的 TNA 聚合酶，其催化速率为 1 nt s-1 及 99% 的保真度。封闭三元复合物的晶体结构揭示了重塑活性位点口袋以提高 TNA 合成活性所需的结构变化程度。这些数据共同证明了重组作为 XNA 聚合酶进化策略的重要性，对生物技术和医学具有相当大的实用价值。
{"title":"Directed evolution of a highly efficient TNA polymerase achieved by homologous recombination","authors":"Victoria A. Maola, Eric J. Yik, Mohammad Hajjar, Joy J. Lee, Manuel J. Holguin, Riley N. Quijano, Kalvin K. Nguyen, Katherine L. Ho, Jenny V. Medina, Nicholas Chim, John C. Chaput","doi":"10.1038/s41929-024-01233-1","DOIUrl":"10.1038/s41929-024-01233-1","url":null,"abstract":"Reprogramming DNA polymerases to synthesize xeno-nucleic acids (XNAs) is an important challenge that tests current enzyme engineering tools. Here we describe an evolutionary campaign aimed at generating an XNA polymerase that can efficiently make α-l-threofuranosyl nucleic acid (TNA)—an artificial genetic polymer that is recalcitrant to nucleases and resistant to acid-mediated degradation. Starting from a homologous recombination library, iterative cycles of selection were performed to traverse the fitness landscape in search of neutral mutations with increased evolutionary potential. Subsequent directed evolution of focused mutagenic libraries yielded 10–92, a newly engineered TNA polymerase that functions with a catalytic rate of ∼1 nt s−1 and >99% fidelity. A crystal structure of the closed ternary complex reveals the degree of structural change required to remodel the active site pocket for improved TNA synthesis activity. Together, these data demonstrate the importance of recombination as a strategy for evolving XNA polymerases with considerable practical value for biotechnology and medicine. The catalytic power of DNA polymerases for artificial genetic polymer (XNA) synthesis remains underdeveloped. Now, the evolution and structure of an α-l-threofuranosyl nucleic acid polymerase is described that achieves XNA synthesis with ∼1 nt s−1 and >99% template-copying fidelity.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1173-1185"},"PeriodicalIF":42.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330403","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 : 2024-09-30DOI: 10.1038/s41929-024-01232-2
Francesc Valls Mascaró, Marc T. M. Koper, Marcel J. Rost
The atomic-scale surface structure plays a major role in the electrochemical behaviour of a catalyst. The electrocatalytic activity towards many relevant reactions, such as the oxygen reduction reaction on platinum, exhibits a linear dependency with the number of steps until this linear scaling breaks down at high step densities. Here we show, using Pt(111)-vicinal surfaces and in situ electrochemical scanning tunnelling microscopy, that this anomalous behaviour at high step densities has a structural origin and is attributed to the bunching of closely spaced steps. While Pt(554) presents parallel single steps and terrace widths that correspond to its nominal, expected value, most steps on Pt(553) are bunched. Our findings challenge the common assumption in electrochemistry that all stepped surfaces are composed of homogeneously spaced steps of monoatomic height and can successfully explain the anomalous trends documented in the literature linking step density to both activity and potential of zero total charge. The electrocatalytic activity of metal catalysts commonly exhibits a positive linear correlation with the presence of steps, but this dependency breaks down for Pt catalysts with high step densities. Now, using in situ electrochemical scanning tunnelling microscopy, it is shown that this is due to the bunching of closely spaced steps, forming double and triple steps.
{"title":"Step bunching instability and its effects in electrocatalysis on platinum surfaces","authors":"Francesc Valls Mascaró, Marc T. M. Koper, Marcel J. Rost","doi":"10.1038/s41929-024-01232-2","DOIUrl":"10.1038/s41929-024-01232-2","url":null,"abstract":"The atomic-scale surface structure plays a major role in the electrochemical behaviour of a catalyst. The electrocatalytic activity towards many relevant reactions, such as the oxygen reduction reaction on platinum, exhibits a linear dependency with the number of steps until this linear scaling breaks down at high step densities. Here we show, using Pt(111)-vicinal surfaces and in situ electrochemical scanning tunnelling microscopy, that this anomalous behaviour at high step densities has a structural origin and is attributed to the bunching of closely spaced steps. While Pt(554) presents parallel single steps and terrace widths that correspond to its nominal, expected value, most steps on Pt(553) are bunched. Our findings challenge the common assumption in electrochemistry that all stepped surfaces are composed of homogeneously spaced steps of monoatomic height and can successfully explain the anomalous trends documented in the literature linking step density to both activity and potential of zero total charge. The electrocatalytic activity of metal catalysts commonly exhibits a positive linear correlation with the presence of steps, but this dependency breaks down for Pt catalysts with high step densities. Now, using in situ electrochemical scanning tunnelling microscopy, it is shown that this is due to the bunching of closely spaced steps, forming double and triple steps.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 11","pages":"1165-1172"},"PeriodicalIF":42.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329493","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 : 2024-09-24DOI: 10.1038/s41929-024-01222-4
Xiaofei Guan
Traditional heterogeneous catalytic processes primarily hinge on the reactivity of solids. Now, a liquid metal catalyst based on a Cu–Ga binary system with dynamic structure and intriguing properties opens up an alternative for the conventional Haber–Bosch process for ammonia synthesis.
{"title":"Without that crystalline touch","authors":"Xiaofei Guan","doi":"10.1038/s41929-024-01222-4","DOIUrl":"10.1038/s41929-024-01222-4","url":null,"abstract":"Traditional heterogeneous catalytic processes primarily hinge on the reactivity of solids. Now, a liquid metal catalyst based on a Cu–Ga binary system with dynamic structure and intriguing properties opens up an alternative for the conventional Haber–Bosch process for ammonia synthesis.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"7 9","pages":"961-962"},"PeriodicalIF":42.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313977","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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