It remains challenging for enzymatic synthesis of long DNA using a terminal deoxynucleotidyl transferase (TdT) due to its limited activity against intermediates containing a 3′ terminal hairpin structure that occurred during synthesis. Reverting DNA to a single strand at high temperature is a solution, while TdT exhibits limited thermostability. Here, we explored a computational design strategy to enhance the thermostability of TdT. Ten sequences designed by ProteinMPNN improved the Tm value by up to 24.3 °C. Two rounds design using PROSS generated the most stable and active variant M7–8 with a half-life improved by 77-fold. The M7–8 variant was successfully used for highly efficient extension of a 52 nt DNA oligonucleotide containing a hairpin structure, which makes it promising for use in the de novo synthesis of long DNA.
{"title":"Computational Design of a Thermostable and Highly Active Terminal Deoxynucleotidyl Transferase for Synthesis of Long De Novo DNA Molecules","authors":"Yadan Niu, Binbin Chen, Huijun Zhang, Wenlong Zheng, Jianping Wu, Lirong Yang, Meng Yang, Haoran Yu","doi":"10.1021/acscatal.5c01571","DOIUrl":"https://doi.org/10.1021/acscatal.5c01571","url":null,"abstract":"It remains challenging for enzymatic synthesis of long DNA using a terminal deoxynucleotidyl transferase (TdT) due to its limited activity against intermediates containing a 3′ terminal hairpin structure that occurred during synthesis. Reverting DNA to a single strand at high temperature is a solution, while TdT exhibits limited thermostability. Here, we explored a computational design strategy to enhance the thermostability of TdT. Ten sequences designed by ProteinMPNN improved the <i>T</i><sub>m</sub> value by up to 24.3 °C. Two rounds design using PROSS generated the most stable and active variant M7–8 with a half-life improved by 77-fold. The M7–8 variant was successfully used for highly efficient extension of a 52 nt DNA oligonucleotide containing a hairpin structure, which makes it promising for use in the de novo synthesis of long DNA.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"6 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The low selectivity for N2 in the oxidation of NH3 over commercial Pt/Al2O3 catalysts is primarily due to the overoxidation of NH3 facilitated by Pt sites, leading to the formation of unwanted byproducts such as N2O and NO. In this study, we present a novel strategy to enhance N2 selectivity while maintaining NH3 conversion by constructing Pt–O–Cu dual sites. These dual sites exhibit synergistic acid-redox characteristics through surface electron transfer mediated by bridged lattice oxygen. Additionally, the ability of surface-adsorbed oxygen to exchange with lattice oxygen is significantly improved. The electron-deficient Cu sites enhance NH3 adsorption by providing empty 3d orbitals, while the electron-rich Pt sites promote NH3 dehydrogenation. Subsequently, the formation of –NH or –N intermediates at the Pt sites can react with adsorbed NH3 on the Cu sites to produce N2, predominantly following the integrated selective catalytic reduction mechanism. The optimized dual-site catalyst achieves over 95% NH3 conversion and N2 selectivity at 180 °C.
{"title":"Mechanistic Insights into Ammonia Oxidation over Electron Transfer-Induced Pt–O–Cu Dual Sites","authors":"Yifan Li, Jiaxing Li, Lin Chen, Yunpeng Long, Xing Yuan, Junhua Li, Yue Peng","doi":"10.1021/acscatal.5c00862","DOIUrl":"https://doi.org/10.1021/acscatal.5c00862","url":null,"abstract":"The low selectivity for N<sub>2</sub> in the oxidation of NH<sub>3</sub> over commercial Pt/Al<sub>2</sub>O<sub>3</sub> catalysts is primarily due to the overoxidation of NH<sub>3</sub> facilitated by Pt sites, leading to the formation of unwanted byproducts such as N<sub>2</sub>O and NO. In this study, we present a novel strategy to enhance N<sub>2</sub> selectivity while maintaining NH<sub>3</sub> conversion by constructing Pt–O–Cu dual sites. These dual sites exhibit synergistic acid-redox characteristics through surface electron transfer mediated by bridged lattice oxygen. Additionally, the ability of surface-adsorbed oxygen to exchange with lattice oxygen is significantly improved. The electron-deficient Cu sites enhance NH<sub>3</sub> adsorption by providing empty 3d orbitals, while the electron-rich Pt sites promote NH<sub>3</sub> dehydrogenation. Subsequently, the formation of –NH or –N intermediates at the Pt sites can react with adsorbed NH<sub>3</sub> on the Cu sites to produce N<sub>2</sub>, predominantly following the integrated selective catalytic reduction mechanism. The optimized dual-site catalyst achieves over 95% NH<sub>3</sub> conversion and N<sub>2</sub> selectivity at 180 °C.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"27 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842114","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}
Copper-based catalysts are widely utilized for methanol steam reforming (MSR) reactions. However, improving their performance and achieving a deeper understanding of the reaction mechanism remain significant challenges. Herein, a series of Cu-y%CrOx/Al2O3 catalysts were synthesized. The optimal Cu-7%CrOx/Al2O3 catalyst achieved a high CH3OH conversion of 93.2%, a low CO selectivity of 0.16%, and a competitive hydrogen production rate of 1142.7 mmol gcat–1 h–1 at 260 °C with a weight space velocity of 14.6 h–1, significantly outperforming the Cu/Al2O3 catalyst. Combined in situ spectroscopy and surface reaction experiments revealed that the MSR reaction on both catalysts predominantly followed the HCOO* pathway. This involves the dehydrogenation of CH3OH to CH3O*, followed by oxidation to HCOO*, and then decomposition to produce H2 and CO2, with the conversion of CH3O* to HCOO* being the rate-determining step (RDS). The steam acted as a promoter for the conversions of CH3O* and HCOO*. A small amount of formaldehyde (HCHO) derived from CH3O* dehydrogenation tends to dissociate, forming the byproduct CO rather than converting to HCOO*. Due to the promoting effect of CrOx, improved Cu dispersion, the Cu+/Cu0 ratio of around 1.0, and increased active oxygen species facilitate the RDS of CH3O* to HCOO* and the oxidation of CO, leading to an enhanced hydrogen production rate and CO2 selectivity on Cu-7%CrOx/Al2O3 compared to Cu/Al2O3.
{"title":"Enhancing the Reactivity of Cu/Al2O3 for Methanol Steam Reforming through adding CrOx: Unraveling Reaction Pathways and the Mechanism for Improvement","authors":"Lifang Jiang, Shaoteng Yuan, Jiamei Ma, Shaorong Deng, Xiuzhong Fang, Xianglan Xu, Hao Meng, Xiang Wang","doi":"10.1021/acscatal.5c00438","DOIUrl":"https://doi.org/10.1021/acscatal.5c00438","url":null,"abstract":"Copper-based catalysts are widely utilized for methanol steam reforming (MSR) reactions. However, improving their performance and achieving a deeper understanding of the reaction mechanism remain significant challenges. Herein, a series of Cu-<i>y</i>%CrO<sub><i>x</i></sub>/Al<sub>2</sub>O<sub>3</sub> catalysts were synthesized. The optimal Cu-7%CrO<sub><i>x</i></sub>/Al<sub>2</sub>O<sub>3</sub> catalyst achieved a high CH<sub>3</sub>OH conversion of 93.2%, a low CO selectivity of 0.16%, and a competitive hydrogen production rate of 1142.7 mmol g<sub>cat</sub><sup>–1</sup> h<sup>–1</sup> at 260 °C with a weight space velocity of 14.6 h<sup>–1</sup>, significantly outperforming the Cu/Al<sub>2</sub>O<sub>3</sub> catalyst. Combined <i>in situ</i> spectroscopy and surface reaction experiments revealed that the MSR reaction on both catalysts predominantly followed the HCOO* pathway. This involves the dehydrogenation of CH<sub>3</sub>OH to CH<sub>3</sub>O*, followed by oxidation to HCOO*, and then decomposition to produce H<sub>2</sub> and CO<sub>2</sub>, with the conversion of CH<sub>3</sub>O* to HCOO* being the rate-determining step (RDS). The steam acted as a promoter for the conversions of CH<sub>3</sub>O* and HCOO*. A small amount of formaldehyde (HCHO) derived from CH<sub>3</sub>O* dehydrogenation tends to dissociate, forming the byproduct CO rather than converting to HCOO*. Due to the promoting effect of CrO<sub><i>x</i></sub>, improved Cu dispersion, the Cu<sup>+</sup>/Cu<sup>0</sup> ratio of around 1.0, and increased active oxygen species facilitate the RDS of CH<sub>3</sub>O* to HCOO* and the oxidation of CO, leading to an enhanced hydrogen production rate and CO<sub>2</sub> selectivity on Cu-7%CrO<sub><i>x</i></sub>/Al<sub>2</sub>O<sub>3</sub> compared to Cu/Al<sub>2</sub>O<sub>3</sub>.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"90 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842109","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 : 2025-04-17DOI: 10.1021/acscatal.5c00519
Mengru Li, Axel Groß, R. Jürgen Behm
Continuing our investigation of electronic metal–support interactions (EMSIs) in heterogeneous catalysis, we have investigated the influence of the position and the number of O-vacancies on their stabilization by the Ru nanorod, on the charge transfer from the support to the metal, and on CO adsorption on the Ru nanorod. Employing density functional theory-based calculations and using a model system consisting of a ZrO2(111) support and a three-layer Ru nanorod, we find that O-vacancies are significantly stabilized only if they are in direct contact with the Ru nanorod, with the extent of stabilization depending on the distance between vacancy and the nearest Ru atom at the interface. Vacancy formation beside the Ru nanorod or in deeper layers of the support is not enhanced by the metal. The Ru-induced stabilization of the O-vacancies is closely coupled with the charge transfer from the support to the metal upon vacancy formation, which is true also in the presence of neighboring O-vacancies. The CO adsorption energy can be substantially modified by four characteristic effects, including charge transfer from the support to the metal, coordination effects, a combination of COad-induced deformation energies and changes in the interface energy and direct interactions between CO and partly reduced Zr surface ions directly neighboring to an O-vacancy, depending on the adsorption site and on the number and positions of the O-vacancies. Thus, it is not possible to completely describe the adsorption properties by using the d-band model, in particular, not for adsorption on the interface sites. The general relevance of these findings for adsorption and catalytic reactions is discussed.
{"title":"Proximity Effects in Electronic Metal–Support Interactions: O-Vacancy Formation and CO Adsorption on Ru/ZrO2 Model Catalysts","authors":"Mengru Li, Axel Groß, R. Jürgen Behm","doi":"10.1021/acscatal.5c00519","DOIUrl":"https://doi.org/10.1021/acscatal.5c00519","url":null,"abstract":"Continuing our investigation of electronic metal–support interactions (EMSIs) in heterogeneous catalysis, we have investigated the influence of the position and the number of O-vacancies on their stabilization by the Ru nanorod, on the charge transfer from the support to the metal, and on CO adsorption on the Ru nanorod. Employing density functional theory-based calculations and using a model system consisting of a ZrO<sub>2</sub>(111) support and a three-layer Ru nanorod, we find that O-vacancies are significantly stabilized only if they are in direct contact with the Ru nanorod, with the extent of stabilization depending on the distance between vacancy and the nearest Ru atom at the interface. Vacancy formation beside the Ru nanorod or in deeper layers of the support is not enhanced by the metal. The Ru-induced stabilization of the O-vacancies is closely coupled with the charge transfer from the support to the metal upon vacancy formation, which is true also in the presence of neighboring O-vacancies. The CO adsorption energy can be substantially modified by four characteristic effects, including charge transfer from the support to the metal, coordination effects, a combination of CO<sub>ad</sub>-induced deformation energies and changes in the interface energy and direct interactions between CO and partly reduced Zr surface ions directly neighboring to an O-vacancy, depending on the adsorption site and on the number and positions of the O-vacancies. Thus, it is not possible to completely describe the adsorption properties by using the d-band model, in particular, not for adsorption on the interface sites. The general relevance of these findings for adsorption and catalytic reactions is discussed.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"128 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842110","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 : 2025-04-17DOI: 10.1021/acscatal.5c00528
Chunli Ai, Fan Dang, Jialei Wan, Zeyu Jiang, Yani Wu, Jicheng Liu, Han Xu, Yadi Wang, Yanfei Jian, Mingjiao Tian, Changwei Chen, Yanke Yu, Chi He
Accelerating deep oxidation while restraining the hazardous intermediate formation remains a great challenge in oxygenated volatile organic compounds (OVOCs) catalytic purification. Herein, we found that the modulation of electronic metal–support interactions (EMSIs) in Pd/WOx/Al2O3 catalysts significantly facilitates the deep oxidation of methyl ethyl ketone (MEK) and markedly enhances the CO2 selectivity. Over the Pd/WOx/Al2O3 catalyst, 90% of MEK can be fully oxidized at just 140 °C with a low apparent activation energy (Ea) of 19.65 kJ·mol–1, much superior to that of the commercial Pd/Al2O3 catalyst (Ea of 80.81 kJ·mol–1). The EMSIs promote charge redistribution through the unified Pd-WOx sites, which modulates the d-band structure of highly dispersed Pd sites and strengthens the adsorption and activation of reactants. The positively charged Pd2+ species are dominant in activating MEK molecules at low temperatures, and the stretched W–O bonds enhance the activation of lattice oxygen species to participate in subsequent oxidation, ensuring the rapid total oxidation of MEK molecules via the Mars-van Krevelen mechanism. Furthermore, the bifunctional Pd-WOx sites can also facilitate the dissociation of H2O and CH2Cl2 molecules, enhancing the water-vapor and chlorine resistance of the Pd/WOx/Al2O3 catalyst, which expands the potential toward practical applications. This work sheds significant guidance for researchers to engineer efficacious catalysts toward industrial OVOCs deep elimination.
{"title":"Enhancing Deep Mineralization and Chlorine Resistance in Methyl Ethyl Ketone Destruction by Taming Synergy of WOx and Pd Sites","authors":"Chunli Ai, Fan Dang, Jialei Wan, Zeyu Jiang, Yani Wu, Jicheng Liu, Han Xu, Yadi Wang, Yanfei Jian, Mingjiao Tian, Changwei Chen, Yanke Yu, Chi He","doi":"10.1021/acscatal.5c00528","DOIUrl":"https://doi.org/10.1021/acscatal.5c00528","url":null,"abstract":"Accelerating deep oxidation while restraining the hazardous intermediate formation remains a great challenge in oxygenated volatile organic compounds (OVOCs) catalytic purification. Herein, we found that the modulation of electronic metal–support interactions (EMSIs) in Pd/WO<sub><i>x</i></sub>/Al<sub>2</sub>O<sub>3</sub> catalysts significantly facilitates the deep oxidation of methyl ethyl ketone (MEK) and markedly enhances the CO<sub>2</sub> selectivity. Over the Pd/WO<sub><i>x</i></sub>/Al<sub>2</sub>O<sub>3</sub> catalyst, 90% of MEK can be fully oxidized at just 140 °C with a low apparent activation energy (<i>E</i><sub>a</sub>) of 19.65 kJ·mol<sup>–1</sup>, much superior to that of the commercial Pd/Al<sub>2</sub>O<sub>3</sub> catalyst (<i>E</i><sub>a</sub> of 80.81 kJ·mol<sup>–1</sup>). The EMSIs promote charge redistribution through the unified Pd-WO<sub><i>x</i></sub> sites, which modulates the <i>d</i>-band structure of highly dispersed Pd sites and strengthens the adsorption and activation of reactants. The positively charged Pd<sup>2+</sup> species are dominant in activating MEK molecules at low temperatures, and the stretched W–O bonds enhance the activation of lattice oxygen species to participate in subsequent oxidation, ensuring the rapid total oxidation of MEK molecules via the Mars-van Krevelen mechanism. Furthermore, the bifunctional Pd-WO<sub><i>x</i></sub> sites can also facilitate the dissociation of H<sub>2</sub>O and CH<sub>2</sub>Cl<sub>2</sub> molecules, enhancing the water-vapor and chlorine resistance of the Pd/WO<sub><i>x</i></sub>/Al<sub>2</sub>O<sub>3</sub> catalyst, which expands the potential toward practical applications. This work sheds significant guidance for researchers to engineer efficacious catalysts toward industrial OVOCs deep elimination.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"30 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846741","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 : 2025-04-17DOI: 10.1021/acscatal.5c01282
Tao Liu, Tuanli Yao, Ran Fang, Xiangyang Qin
Chiral C3-tertiary indolines serve as crucial structural scaffolds in biologically active molecules and natural products. However, the asymmetric synthesis of such compounds remains largely underexplored. In this work, we report a palladium-catalyzed intramolecular Heck strategy that can override the intrinsic aromatization and enable selective access to enantiomerically enriched 3-(2-oxoethyl)indolines (up to 96% ee). The key to the success of this strategy is introducing a hydroxy group at the α-position of alkene moieties of N-allyl-2-iodoanilines, which undergo regioselective β-hydride elimination. We demonstrate the synthetic utility of this strategy by performing downstream transformations of the products based on aldehyde groups. Density functional theory (DFT) calculations elucidate the mechanism and stereoinduction.
{"title":"Palladium-Catalyzed Enantioselective Intramolecular Heck Reaction to Access Chiral C3-Tertiary Indolines","authors":"Tao Liu, Tuanli Yao, Ran Fang, Xiangyang Qin","doi":"10.1021/acscatal.5c01282","DOIUrl":"https://doi.org/10.1021/acscatal.5c01282","url":null,"abstract":"Chiral C3-tertiary indolines serve as crucial structural scaffolds in biologically active molecules and natural products. However, the asymmetric synthesis of such compounds remains largely underexplored. In this work, we report a palladium-catalyzed intramolecular Heck strategy that can override the intrinsic aromatization and enable selective access to enantiomerically enriched 3-(2-oxoethyl)indolines (up to 96% ee). The key to the success of this strategy is introducing a hydroxy group at the α-position of alkene moieties of <i>N</i>-allyl-2-iodoanilines, which undergo regioselective β-hydride elimination. We demonstrate the synthetic utility of this strategy by performing downstream transformations of the products based on aldehyde groups. Density functional theory (DFT) calculations elucidate the mechanism and stereoinduction.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"17 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846670","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 : 2025-04-17DOI: 10.1021/acscatal.5c01642
Sven Timmann, Moritz T. H. Dilchert, Jörg Dietzel, Verena S. Pöltl, Marc R. Wennekamp, Christopher Golz, Manuel Alcarazo
A simple protocol for the multigram-scale synthesis of 5-(1-(trifluoromethyl)cyclopropyl)dibenzothiophenium triflate is reported. This benchtop-stable reagent efficiently releases 1-(trifluoromethyl)cyclopropyl radicals under mild photochemical conditions, enabling the straightforward incorporation of that privileged chemotype at previously nonfunctionalized positions of (hetero)arenes and silyl enol ethers. The trifluoromethylcyclopropanation protocols herein reported are associated with an exceedingly broad substrate scope, remarkable functional group compatibility, high regioselectivity, and synthetically useful yields, making this reagent especially suitable for the preparation of medicinally relevant building blocks.
{"title":"A Photocatalytic Approach to Radical 1-(Trifluoromethyl)cyclopropanation","authors":"Sven Timmann, Moritz T. H. Dilchert, Jörg Dietzel, Verena S. Pöltl, Marc R. Wennekamp, Christopher Golz, Manuel Alcarazo","doi":"10.1021/acscatal.5c01642","DOIUrl":"https://doi.org/10.1021/acscatal.5c01642","url":null,"abstract":"A simple protocol for the multigram-scale synthesis of 5-(1-(trifluoromethyl)cyclopropyl)dibenzothiophenium triflate is reported. This benchtop-stable reagent efficiently releases 1-(trifluoromethyl)cyclopropyl radicals under mild photochemical conditions, enabling the straightforward incorporation of that privileged chemotype at previously nonfunctionalized positions of (hetero)arenes and silyl enol ethers. The trifluoromethylcyclopropanation protocols herein reported are associated with an exceedingly broad substrate scope, remarkable functional group compatibility, high regioselectivity, and synthetically useful yields, making this reagent especially suitable for the preparation of medicinally relevant building blocks.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"47 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849893","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 : 2025-04-16DOI: 10.1021/acscatal.5c01177
Zhenzhen Guo, Jinxiang Ye, Yingying Zhang, Danni Wang, Xiaoqian Yu, Chong Li, Yangjie Wu, Ze-Shui Liu
Silacycles are essential structural motifs in silicon-containing functional molecules, which are widely applied in the fields of synthetic chemistry, materials science, and pharmaceuticals. However, the synthesis of silacycles especially medium-sized ones remains a formidable challenge. Herein, we report a general and modular platform technology for the construction of eight-membered benzosilacycles by palladium-catalyzed alkyne insertion/C–H activation/ring expansion cascade. Readily available aryl halides, alkynes, and silacyclobutanes are used as the building blocks, laying the foundation for the diversity-oriented synthesis of these scaffolds (>80 examples). Other features include excellent regioselectivities and chemoselectivities, broad functional group tolerance, good step economy, and scalability. This method is also amenable for the synthesis of fused benzosilacycles and dibenzosilacycles that are otherwise difficult to access. Additionally, the reaction mechanism and the origins of regioselectivity are elucidated by control experiments and density functional theory calculations.
{"title":"Modular and Regioselective Synthesis of Eight-Membered Benzosilacycles Enabled by Ring Expansion of Silacyclobutanes with Aryl Halides and Alkynes","authors":"Zhenzhen Guo, Jinxiang Ye, Yingying Zhang, Danni Wang, Xiaoqian Yu, Chong Li, Yangjie Wu, Ze-Shui Liu","doi":"10.1021/acscatal.5c01177","DOIUrl":"https://doi.org/10.1021/acscatal.5c01177","url":null,"abstract":"Silacycles are essential structural motifs in silicon-containing functional molecules, which are widely applied in the fields of synthetic chemistry, materials science, and pharmaceuticals. However, the synthesis of silacycles especially medium-sized ones remains a formidable challenge. Herein, we report a general and modular platform technology for the construction of eight-membered benzosilacycles by palladium-catalyzed alkyne insertion/C–H activation/ring expansion cascade. Readily available aryl halides, alkynes, and silacyclobutanes are used as the building blocks, laying the foundation for the diversity-oriented synthesis of these scaffolds (>80 examples). Other features include excellent regioselectivities and chemoselectivities, broad functional group tolerance, good step economy, and scalability. This method is also amenable for the synthesis of fused benzosilacycles and dibenzosilacycles that are otherwise difficult to access. Additionally, the reaction mechanism and the origins of regioselectivity are elucidated by control experiments and density functional theory calculations.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"121 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837428","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 : 2025-04-16DOI: 10.1021/acscatal.5c00835
Qian Zhang, Yixin Zhang, Zixin Deng, Yi Yu
Benzoxazole is an important heterocycle building block frequently found in medicinal compounds and naturally occurring alkaloids. Deciphering the biosynthetic machinery of benzoxazole would facilitate the efficient synthesis of benzoxazole-based drugs. Nataxazole represents a unique alkaloid class containing two benzoxazole moieties (A and B). Previous studies have established the enzymatic mechanism underlying the biosynthesis of benzoxazole moiety A (fusion of two 3-hydroxyanthranilic acid molecules). Here, we report that the same biosynthetic machinery of nataxazole employs a different logic, which involves a 3-oxoacyl-ACP synthase III-like enzyme (NatS), to assemble benzoxazole moiety B (fusion of 3-hydroxyanthranilic acid with 6-methylsalicylic acid). Biochemical and structural characterization indicated that NatS catalyzes a transacylation reaction to generate an unstable ester intermediate, which immediately undergoes cyclization and dehydration catalyzed by the amidohydrolase NatAM to give benzoxazole moiety B. Interestingly, NatS can also catalyze C–N and C–S bond formation and exhibits remarkable substrate promiscuity, inspiring us to synthesize various benzoheterocycles following the assembly logic of moiety B. Together with our investigation into the biosynthesis of nataxazole analogue A33853, we further identified two key amino acids responsible for NatAM’s substrate recognition to generate two benzoxazole moieties in nataxazole. Finally, we successfully developed a chemoenzymatic approach to produce transthyretin stabilizer Tafamidis (Vyndamax). Therefore, our study found the missing piece of the benzoxazole biosynthesis puzzle, providing a promising strategy to create diverse types of benzoheterocycle compounds.
{"title":"A KAS III-like Enzyme and an Amidohydrolase in Nataxazole Biosynthesis Direct Formation of the Benzoheterocycle Moiety","authors":"Qian Zhang, Yixin Zhang, Zixin Deng, Yi Yu","doi":"10.1021/acscatal.5c00835","DOIUrl":"https://doi.org/10.1021/acscatal.5c00835","url":null,"abstract":"Benzoxazole is an important heterocycle building block frequently found in medicinal compounds and naturally occurring alkaloids. Deciphering the biosynthetic machinery of benzoxazole would facilitate the efficient synthesis of benzoxazole-based drugs. Nataxazole represents a unique alkaloid class containing two benzoxazole moieties (A and B). Previous studies have established the enzymatic mechanism underlying the biosynthesis of benzoxazole moiety A (fusion of two 3-hydroxyanthranilic acid molecules). Here, we report that the same biosynthetic machinery of nataxazole employs a different logic, which involves a 3-oxoacyl-ACP synthase III-like enzyme (NatS), to assemble benzoxazole moiety B (fusion of 3-hydroxyanthranilic acid with 6-methylsalicylic acid). Biochemical and structural characterization indicated that NatS catalyzes a transacylation reaction to generate an unstable ester intermediate, which immediately undergoes cyclization and dehydration catalyzed by the amidohydrolase NatAM to give benzoxazole moiety B. Interestingly, NatS can also catalyze C–N and C–S bond formation and exhibits remarkable substrate promiscuity, inspiring us to synthesize various benzoheterocycles following the assembly logic of moiety B. Together with our investigation into the biosynthesis of nataxazole analogue A33853, we further identified two key amino acids responsible for NatAM’s substrate recognition to generate two benzoxazole moieties in nataxazole. Finally, we successfully developed a chemoenzymatic approach to produce transthyretin stabilizer Tafamidis (Vyndamax). Therefore, our study found the missing piece of the benzoxazole biosynthesis puzzle, providing a promising strategy to create diverse types of benzoheterocycle compounds.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"27 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842116","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 : 2025-04-16DOI: 10.1021/acscatal.5c00392
Lauren Kilburn, Diamarys Salomé Rivera, Elizabeth E. Bickel Rogers, Rajamani Gounder, David D. Hibbitts
The consequences of Brønsted acid site location in MFI zeolites were investigated for propene oligomerization. Adsorbates in MFI may reside in smaller channels (∼5.5 Å diam.) or larger channel intersections (∼7 Å diam.), with tighter confinement expected to enhance both stabilizing dispersive interactions and destabilizing steric constraints. MFI samples synthesized using tetrapropylammonium (TPA+) as the structure directing agent have higher fractions of acid sites near intersections, while samples synthesized with 1,4-diazabicyclo[2.2.2]octane (DABCO) or ethylenediamine (EDA) have higher fractions of acid sites within channels. Measured propene dimerization rates (per H+, 315 kPa C3H6, 503 K, 1.6 H+/u.c.) are ∼9 times higher on MFI-DABCO/MFI-EDA than MFI-TPA. Because propene oligomerization is transport-limited in MFI at these conditions, experimentally measured rates are proportional to both effective kinetic (keff) and diffusion (De) constants. DFT was therefore used to investigate the kinetic influences of void environment in isolation of transport effects. Adsorption free energies for C3 and C6 alkenes and dimerization free energy barriers were calculated at all 12 T-sites present in the MFI framework and all accessible O-sites around each T-site. C3 preferentially adsorbs as H-bonded propene with similar energies in all void environments, while C6 alkenes are destabilized by 10–56 kJ mol–1 and dimerization transition states are destabilized by 29–102 kJ mol–1, on average, in the channels relative to intersections. The stability of C3 and C6 alkenes and dimerization transition states is largely governed by steric penalties arising from distortion of the MFI framework that outweigh stronger dispersive interactions with decreasing void size, even for species as small as C3. Given that DFT predicts keff values are lower at acid sites in smaller channel voids of MFI, higher measured rates on MFI samples synthesized using DABCO or EDA must reflect less severe diffusion restrictions and, in turn, higher De values.
{"title":"Assessing the Influence of Void Environment in MFI Zeolites on Propene Oligomerization Kinetics Using a Combined Computational and Experimental Approach","authors":"Lauren Kilburn, Diamarys Salomé Rivera, Elizabeth E. Bickel Rogers, Rajamani Gounder, David D. Hibbitts","doi":"10.1021/acscatal.5c00392","DOIUrl":"https://doi.org/10.1021/acscatal.5c00392","url":null,"abstract":"The consequences of Brønsted acid site location in MFI zeolites were investigated for propene oligomerization. Adsorbates in MFI may reside in smaller channels (∼5.5 Å diam.) or larger channel intersections (∼7 Å diam.), with tighter confinement expected to enhance both stabilizing dispersive interactions and destabilizing steric constraints. MFI samples synthesized using tetrapropylammonium (TPA<sup>+</sup>) as the structure directing agent have higher fractions of acid sites near intersections, while samples synthesized with 1,4-diazabicyclo[2.2.2]octane (DABCO) or ethylenediamine (EDA) have higher fractions of acid sites within channels. Measured propene dimerization rates (per H<sup>+</sup>, 315 kPa C<sub>3</sub>H<sub>6</sub>, 503 K, 1.6 H<sup>+</sup>/u.c.) are ∼9 times higher on MFI-DABCO/MFI-EDA than MFI-TPA. Because propene oligomerization is transport-limited in MFI at these conditions, experimentally measured rates are proportional to both effective kinetic (<i>k</i><sub>eff</sub>) and diffusion (<i>D</i><sub>e</sub>) constants. DFT was therefore used to investigate the kinetic influences of void environment in isolation of transport effects. Adsorption free energies for C<sub>3</sub> and C<sub>6</sub> alkenes and dimerization free energy barriers were calculated at all 12 T-sites present in the MFI framework and all accessible O-sites around each T-site. C<sub>3</sub> preferentially adsorbs as H-bonded propene with similar energies in all void environments, while C<sub>6</sub> alkenes are destabilized by 10–56 kJ mol<sup>–1</sup> and dimerization transition states are destabilized by 29–102 kJ mol<sup>–1</sup>, on average, in the channels relative to intersections. The stability of C<sub>3</sub> and C<sub>6</sub> alkenes and dimerization transition states is largely governed by steric penalties arising from distortion of the MFI framework that outweigh stronger dispersive interactions with decreasing void size, even for species as small as C<sub>3</sub>. Given that DFT predicts <i>k</i><sub>eff</sub> values are lower at acid sites in smaller channel voids of MFI, higher measured rates on MFI samples synthesized using DABCO or EDA must reflect less severe diffusion restrictions and, in turn, higher <i>D</i><sub>e</sub> values.","PeriodicalId":9,"journal":{"name":"ACS Catalysis ","volume":"75 2 1","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842115","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：