Long-Fei Wu, Junting Zhang, Robert Cornwell-Arquitt, David A. Hendrix, Aleksandar Radakovic, Jack W. Szostak
The prebiotic formation of RNA building blocks is well-supported experimentally, yet the emergence of sequence- and structure-specific RNA oligomers is generally attributed to biological selection via Darwinian evolution rather than prebiotic chemical selectivity. In this study, we investigated the partitioning of randomized RNA overhangs into ligated products via these two competing pathways using deep sequencing. Comprehensive sequence-reactivity profiles revealed that loop-closing ligation preferentially yields hairpin structures with loop sequences UNNG, CNNG, and GNNA (where N represents A, C, G, or U) under both loose and stringent competing conditions. In contrast, splinted ligation products favor CG-rich overhangs. Notably, the overhang sequences that preferentially partition to loop-closing ligation significantly overlap with the most common biological tetraloops, whereas the overhangs favoring splinted ligation exhibit an inverse correlation with biological tetraloops. These sequence rules enable the high-efficiency assembly of functional ribozymes from short RNAs free from template inhibition. Our findings suggest that the RNA tetraloop structures that are common in biology may have been predisposed and prevalent in the prebiotic pool of RNAs, prior to the advent of Darwinian evolution. We suggest that the one-step prebiotic chemical process of loop-closing ligation could have favored the emergence of the first RNA functions.
{"title":"Selective Nonenzymatic Formation of Biologically Common RNA Hairpins","authors":"Long-Fei Wu, Junting Zhang, Robert Cornwell-Arquitt, David A. Hendrix, Aleksandar Radakovic, Jack W. Szostak","doi":"10.1002/anie.202417370","DOIUrl":"https://doi.org/10.1002/anie.202417370","url":null,"abstract":"The prebiotic formation of RNA building blocks is well-supported experimentally, yet the emergence of sequence- and structure-specific RNA oligomers is generally attributed to biological selection via Darwinian evolution rather than prebiotic chemical selectivity. In this study, we investigated the partitioning of randomized RNA overhangs into ligated products via these two competing pathways using deep sequencing. Comprehensive sequence-reactivity profiles revealed that loop-closing ligation preferentially yields hairpin structures with loop sequences UNNG, CNNG, and GNNA (where N represents A, C, G, or U) under both loose and stringent competing conditions. In contrast, splinted ligation products favor CG-rich overhangs. Notably, the overhang sequences that preferentially partition to loop-closing ligation significantly overlap with the most common biological tetraloops, whereas the overhangs favoring splinted ligation exhibit an inverse correlation with biological tetraloops. These sequence rules enable the high-efficiency assembly of functional ribozymes from short RNAs free from template inhibition. Our findings suggest that the RNA tetraloop structures that are common in biology may have been predisposed and prevalent in the prebiotic pool of RNAs, prior to the advent of Darwinian evolution. We suggest that the one-step prebiotic chemical process of loop-closing ligation could have favored the emergence of the first RNA functions.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"198 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678754","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}
Jingjing Zhang, Yifei Zhang, Zhaoxian Qin, Zhiwen Li, Zhaohui Tong, Zhen Zhao, José A. Gascón, Gao Li
Metal nanoclusters stabilized by N‐heterocyclic carbene (NHC) ligands have attracted increasing interest for their special structures and diverse applications. However, developing synthetic strategies and extending the database of NHC‐protected nanoclusters are still challenging tasks. In this work, a novel and rapid synthetic method is developed to prepare AuAg alloy nanocluster ligated by carbene based on the reactivity of nanoclusters. The rod‐like carbene‐capped bimetal nanocluster, [Au13Ag12(PPh3)8(BMIm)2I8]SbF6 (Au13Ag12:BMIm), was achieved and characterized by a series of techniques. The alloy nanocluster consists of two vertex‐sharing icosahedrons and carbene ligands, phosphine ligands, and I atoms. Interestingly, the introduced carbene ligands show strong coordination capabilities with Au, enhancing the interaction between metal core and ligands. To the best of our knowledge, the carbene‐capped Au13Ag12:BMIm nanocluster is the first of its kind to show higher thermostability and higher sensitivity to light compared with the homogeneously capped analogue nanocluster ([Au13Ag12(PPh3)10I8]SbF6). Density functional theory calculations attribute these properties to a unique delocalization of electrons within the frontier orbitals. Finally, the Au13Ag12:BMIm anchored on NiFe‐LDH exhibits remarkable electrocatalytic activity in the electrosynthesis of urea from NO3− and CO2, achieving a urea production rate of 29.5 mmol gcat–1 h–1 with a Faradaic efficiency of 34% at ‐0.5 V (vs. RHE).
{"title":"How Carbene Ligands Transform AuAg Alloy Nanoclusters for Electrocatalytic Urea Synthesis","authors":"Jingjing Zhang, Yifei Zhang, Zhaoxian Qin, Zhiwen Li, Zhaohui Tong, Zhen Zhao, José A. Gascón, Gao Li","doi":"10.1002/anie.202420993","DOIUrl":"https://doi.org/10.1002/anie.202420993","url":null,"abstract":"Metal nanoclusters stabilized by N‐heterocyclic carbene (NHC) ligands have attracted increasing interest for their special structures and diverse applications. However, developing synthetic strategies and extending the database of NHC‐protected nanoclusters are still challenging tasks. In this work, a novel and rapid synthetic method is developed to prepare AuAg alloy nanocluster ligated by carbene based on the reactivity of nanoclusters. The rod‐like carbene‐capped bimetal nanocluster, [Au13Ag12(PPh3)8(BMIm)2I8]SbF6 (Au13Ag12:BMIm), was achieved and characterized by a series of techniques. The alloy nanocluster consists of two vertex‐sharing icosahedrons and carbene ligands, phosphine ligands, and I atoms. Interestingly, the introduced carbene ligands show strong coordination capabilities with Au, enhancing the interaction between metal core and ligands. To the best of our knowledge, the carbene‐capped Au13Ag12:BMIm nanocluster is the first of its kind to show higher thermostability and higher sensitivity to light compared with the homogeneously capped analogue nanocluster ([Au13Ag12(PPh3)10I8]SbF6). Density functional theory calculations attribute these properties to a unique delocalization of electrons within the frontier orbitals. Finally, the Au13Ag12:BMIm anchored on NiFe‐LDH exhibits remarkable electrocatalytic activity in the electrosynthesis of urea from NO3− and CO2, achieving a urea production rate of 29.5 mmol gcat–1 h–1 with a Faradaic efficiency of 34% at ‐0.5 V (vs. RHE).","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"251 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report herein a directing group-controlled, palladium-catalyzed, regio-, stereo-, and enantiospecific anti-carboxylation of unactivated, internal allenes enabled via the synergistic interplay of a rationally designed bidentate directing group, palladium catalyst, and a multifunctional acetate ligand. The corresponding trans allyl ester was obtained in excellent yields with exclusive δ-regioselectivity and anti-carboxypalladation stereocontrol. The acetate ligand of the palladium catalyst controls the regio-, stereo- and enantioselectivity in the desired transformation. The potential of this concept has been demonstrated by the development of the chiral version of this transformation by using axial-to-central chirality transfer with good yields and enantioselectivities. Detailed investigations, including kinetic studies, order studies, and DFT studies, were performed to validate the ligand-assisted nucleopalladation process and the rationale behind the observed racemization of chiral allenes. The studies also indicated that the anti-carboxypalladation step was the rate-limiting as well as the stereo- and enantiodetermining step.
{"title":"Palladium-Catalyzed, Regio-/Stereo- and Enantiospecific Anti-Carboxylation of Unactivated Internal Allenes","authors":"Prajyot Jayadev Nagtilak, Deveen Rajeshbhai Hirapara, Manoj V. Mane, Akshat Jain, Manmohan Kapur","doi":"10.1002/anie.202419127","DOIUrl":"https://doi.org/10.1002/anie.202419127","url":null,"abstract":"We report herein a directing group-controlled, palladium-catalyzed, regio-, stereo-, and enantiospecific anti-carboxylation of unactivated, internal allenes enabled via the synergistic interplay of a rationally designed bidentate directing group, palladium catalyst, and a multifunctional acetate ligand. The corresponding trans allyl ester was obtained in excellent yields with exclusive δ-regioselectivity and anti-carboxypalladation stereocontrol. The acetate ligand of the palladium catalyst controls the regio-, stereo- and enantioselectivity in the desired transformation. The potential of this concept has been demonstrated by the development of the chiral version of this transformation by using axial-to-central chirality transfer with good yields and enantioselectivities. Detailed investigations, including kinetic studies, order studies, and DFT studies, were performed to validate the ligand-assisted nucleopalladation process and the rationale behind the observed racemization of chiral allenes. The studies also indicated that the anti-carboxypalladation step was the rate-limiting as well as the stereo- and enantiodetermining step.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"170 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673832","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 depletion of natural resources and the extensive use of oxidative processes by humans violate a number of Earth's planetary boundaries, threatening our very existence. Chemistry is largely responsible for this situation, but it is also central to the solutions. Transitioning to a more “reductive” approach—especially using green hydrogen and sustainable chemistry within the framework of a circular economy—is one of the key solutions.
{"title":"Earth: An Oxidative Planet with Limited Atom Resources and Rich Chemistry","authors":"Jairton Dupont, Pedro Lozano","doi":"10.1002/anie.202416459","DOIUrl":"https://doi.org/10.1002/anie.202416459","url":null,"abstract":"The depletion of natural resources and the extensive use of oxidative processes by humans violate a number of Earth's planetary boundaries, threatening our very existence. Chemistry is largely responsible for this situation, but it is also central to the solutions. Transitioning to a more “reductive” approach—especially using green hydrogen and sustainable chemistry within the framework of a circular economy—is one of the key solutions.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"19 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678777","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}
Organolithium reagents, known for their low cost, ready availability, and high reactivity, allow fast cross-coupling under ambient conditions. However, their direct cross-coupling with fluoroalkyl electrophiles remains a formidable challenge due to the easy formation of thermo-unstable fluoroalkyl lithium species during the reaction, which are prone to decomposition via rapid α/β-fluoride elimination. Here, we exploit heteroatom-stabilized allylic anions to harness the exceptional reactivity of organolithium reagents, enabling the compatibility of difluoroalkyl halides and facilitating versatile and precise fluorine functionality introduction under mild conditions. In this process, a nickel-catalyzed difluoroalkylation of β,γ-unsaturated α-amino nitrile derived lithium reagents (N-stabilized allyl lithium reagents) with various difluoroalkyl bromides has been developed, opening a new avenue to access fluorinated compounds through catalytic cross-coupling of organolithium reagents with fluoroalkyl electrophiles. This approach allows for the efficient and precise construction of secondary C(sp3)-CF2R bonds, previously challenging in transition-metal-catalyzed fluoroalkylation reactions due to β-hydride elimination. The rapid fluorine-editing of drugs demonstrates the synthetic versatility and utility of this protocol, showing the perspective in modern drug discovery.
{"title":"Nickel-Catalyzed Difluoroalkylation of β,γ-Unsaturated α-Amino Nitrile Derived Lithium Reagents","authors":"Fei-Fei Tong, Yun-Cheng Luo, Hai-Yang Zhao, Xia-Ping Fu, Xingang Zhang","doi":"10.1002/anie.202417858","DOIUrl":"https://doi.org/10.1002/anie.202417858","url":null,"abstract":"Organolithium reagents, known for their low cost, ready availability, and high reactivity, allow fast cross-coupling under ambient conditions. However, their direct cross-coupling with fluoroalkyl electrophiles remains a formidable challenge due to the easy formation of thermo-unstable fluoroalkyl lithium species during the reaction, which are prone to decomposition via rapid α/β-fluoride elimination. Here, we exploit heteroatom-stabilized allylic anions to harness the exceptional reactivity of organolithium reagents, enabling the compatibility of difluoroalkyl halides and facilitating versatile and precise fluorine functionality introduction under mild conditions. In this process, a nickel-catalyzed difluoroalkylation of β,γ-unsaturated α-amino nitrile derived lithium reagents (N-stabilized allyl lithium reagents) with various difluoroalkyl bromides has been developed, opening a new avenue to access fluorinated compounds through catalytic cross-coupling of organolithium reagents with fluoroalkyl electrophiles. This approach allows for the efficient and precise construction of secondary C(sp3)-CF2R bonds, previously challenging in transition-metal-catalyzed fluoroalkylation reactions due to β-hydride elimination. The rapid fluorine-editing of drugs demonstrates the synthetic versatility and utility of this protocol, showing the perspective in modern drug discovery.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"57 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673768","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}
Xinyu Yu, Xianglang Sun, Zonglong Zhu, Zhong'an Li
In recent years, self-assembled monolayers (SAMs) anchored on metal oxides (MO) have greatly boosted the performance of inverted (p-i-n) perovskite solar cells (PVSCs) by serving as hole-selective contacts due to their distinct advantages in transparency, hole-selectivity, passivation, cost-effectiveness, and processing efficiency. While the intrinsic monolayer nature of SAMs provides unique advantages, it also makes them highly sensitive to external pressure, posing a significant challenge for long-term device stability. At present, the stability issue of SAM-based PVSCs is gradually attracting attention. In this review, we discuss the fundamental stability issues arising from the structural characteristics, operating mechanisms, and roles of SAMs, and highlight representative works on improving their stability. We identify the buried interface stability concerns in three key aspects: 1) SAM/MO interface, 2) SAM inner layer, and 3) SAM/perovskite interface, corresponding to the anchoring group, linker group, and terminal group in the SAMs, respectively. Finally, we have proposed potential strategies for achieving excellent stability in SAM-based buried interfaces, particularly for large-scale and flexible applications. We believe this review will deepen understanding of the relationship between SAM structure and their device performance, thereby facilitating the design of novel SAMs and advancing their eventual commercialization in high-efficiency and stable inverted PVSCs.
近年来，锚定在金属氧化物（MO）上的自组装单层（SAMs）因其在透明度、空穴选择性、钝化、成本效益和加工效率方面的独特优势，通过作为空穴选择性触点，极大地提升了反向（p-i-n）包晶太阳能电池（PVSCs）的性能。虽然 SAMs 固有的单层特性具有独特的优势，但同时也使其对外部压力高度敏感，给器件的长期稳定性带来了巨大挑战。目前，基于 SAM 的 PVSCs 的稳定性问题正逐渐引起人们的关注。在这篇综述中，我们讨论了由 SAM 的结构特征、运行机制和作用引起的基本稳定性问题，并重点介绍了提高其稳定性的代表性工作。我们从三个关键方面确定了被掩埋的界面稳定性问题：1) SAM/MO 界面；2) SAM 内层；3) SAM/过氧化物界面，分别与 SAM 中的锚定基团、连接基团和终端基团相对应。最后，我们提出了实现基于 SAM 的埋藏界面卓越稳定性的潜在策略，尤其适用于大规模和柔性应用。我们相信，这篇综述将加深人们对 SAM 结构与其器件性能之间关系的理解，从而促进新型 SAM 的设计，并推动其在高效、稳定的倒置 PVSC 中的最终商业化。
{"title":"Stabilization Strategies of Buried Interface for Efficient SAM-based Inverted Perovskite Solar Cells","authors":"Xinyu Yu, Xianglang Sun, Zonglong Zhu, Zhong'an Li","doi":"10.1002/anie.202419608","DOIUrl":"https://doi.org/10.1002/anie.202419608","url":null,"abstract":"In recent years, self-assembled monolayers (SAMs) anchored on metal oxides (MO) have greatly boosted the performance of inverted (p-i-n) perovskite solar cells (PVSCs) by serving as hole-selective contacts due to their distinct advantages in transparency, hole-selectivity, passivation, cost-effectiveness, and processing efficiency. While the intrinsic monolayer nature of SAMs provides unique advantages, it also makes them highly sensitive to external pressure, posing a significant challenge for long-term device stability. At present, the stability issue of SAM-based PVSCs is gradually attracting attention. In this review, we discuss the fundamental stability issues arising from the structural characteristics, operating mechanisms, and roles of SAMs, and highlight representative works on improving their stability. We identify the buried interface stability concerns in three key aspects: 1) SAM/MO interface, 2) SAM inner layer, and 3) SAM/perovskite interface, corresponding to the anchoring group, linker group, and terminal group in the SAMs, respectively. Finally, we have proposed potential strategies for achieving excellent stability in SAM-based buried interfaces, particularly for large-scale and flexible applications. We believe this review will deepen understanding of the relationship between SAM structure and their device performance, thereby facilitating the design of novel SAMs and advancing their eventual commercialization in high-efficiency and stable inverted PVSCs.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673799","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}
Yang Ni, Jonathan Lebelt, Milena Barp, Florian Kreuter, Jiaye Jin, Hannah Buttkus, Martin Kretzschmar, Ralf Tonner-Zech, Knut R. Asmis, Tanja Gulder
There is a perpetual need for efficient and mild methods to integrate deuterium atoms into carbon frameworks through late-stage modifications. We have developed a simple and highly effective synthetic route for hydrogen isotope exchange (HIE) in aromatic compounds under ambient conditions. This method utilizes catalytic amounts of hexafluorophosphate (PF6−) in deuterated 1,1,1,3,3,3-hexafluoroisopropanol (HFIP-d1) and D2O. Phenols, anilines, anisoles, and heterocyclic compounds were converted with high yields and excellent deuterium incorporations, which allows for the synthesis of a wide range of deuterated aromatic compounds. Spectroscopic and theoretical studies show that an interactive H-bonding network triggered by HFIP-d1 activates the typically inert P-F bond in PF6- for D2O addition. The thus in-situ formed DPO2F2 triggers then HIE, offering a new way to deuterated building blocks, drugs, and natural-product derivatives with high deuterium incorporation via the activation of strong bonds.
{"title":"Hexafluorophosphate-Triggered Hydrogen Isotope Exchange (HIE) in Fluorinated Environments: A Platform for the Deuteration of Aromatic Compounds via Strong Bond Activation","authors":"Yang Ni, Jonathan Lebelt, Milena Barp, Florian Kreuter, Jiaye Jin, Hannah Buttkus, Martin Kretzschmar, Ralf Tonner-Zech, Knut R. Asmis, Tanja Gulder","doi":"10.1002/anie.202417889","DOIUrl":"https://doi.org/10.1002/anie.202417889","url":null,"abstract":"There is a perpetual need for efficient and mild methods to integrate deuterium atoms into carbon frameworks through late-stage modifications. We have developed a simple and highly effective synthetic route for hydrogen isotope exchange (HIE) in aromatic compounds under ambient conditions. This method utilizes catalytic amounts of hexafluorophosphate (PF6−) in deuterated 1,1,1,3,3,3-hexafluoroisopropanol (HFIP-d1) and D2O. Phenols, anilines, anisoles, and heterocyclic compounds were converted with high yields and excellent deuterium incorporations, which allows for the synthesis of a wide range of deuterated aromatic compounds. Spectroscopic and theoretical studies show that an interactive H-bonding network triggered by HFIP-d1 activates the typically inert P-F bond in PF6- for D2O addition. The thus in-situ formed DPO2F2 triggers then HIE, offering a new way to deuterated building blocks, drugs, and natural-product derivatives with high deuterium incorporation via the activation of strong bonds.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"25 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673793","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}
Maleimide derivatives are privileged reagents for chemically modifying proteins through the Michael addition reaction with cysteine due to their selectivity, operational simplicity, and commercial availability. However, since accessible free cysteine is rarely found in natural proteins, it is highly desirable to find alternative targets to enable direct bioconjugation of proteins with maleimides. In this study, we have developed an operationally simple and straightforward method for the N-terminal modification of proteins without the need for mutagenesis via a copper(II)-mediated [3+2] cycloaddition reaction with maleimides and 2-pyridinecarboxaldehyde (2-PCA) derivatives under non-denaturing conditions at pH 6 and 37 °C in aqueous media. Our method utilizes commercially available maleimides to attach diverse functionalities to various N-terminal amino acids. We demonstrate the preparation of a ternary protein complex cross-linked at the N-termini and dually modified trastuzumab equipped with monomethyl auristatin E (MMAE), a cytotoxic agent, and a Cy5 fluorophore (MMAE–Cy5–trastuzumab). MMAE–Cy5–trastuzumab retained human epidermal growth factor receptor 2 (HER2) recognition activity and exerted cytotoxicity against HER2-positive cells. Furthermore, MMAE–Cy5–trastuzumab allowed successful visualization of HER2-positive cancer cells in mouse tumors. This straightforward method will expand the accessibility of protein conjugates with well-defined structures in a wide range of research fields.
马来酰亚胺衍生物具有选择性强、操作简单和商业化等特点，是通过与半胱氨酸发生迈克尔加成反应对蛋白质进行化学修饰的理想试剂。然而，由于在天然蛋白质中很少能找到可利用的游离半胱氨酸，因此我们非常希望能找到替代目标，使马来酰亚胺能直接对蛋白质进行生物共轭。在这项研究中，我们开发了一种操作简单、直接的方法，在 pH 值为 6、温度为 37 ℃ 的水介质中，在非变性条件下，通过铜（II）介导的马来酰亚胺与 2-吡啶甲醛（2-PCA）衍生物的[3+2]环加成反应对蛋白质进行 N 端修饰，而无需诱变。我们的方法利用市场上可买到的马来酰亚胺将各种官能团附着到各种 N 端氨基酸上。我们展示了一种在 N 端交联的三元蛋白质复合物的制备方法，该复合物与单甲基金丝桃素 E（MMAE）（一种细胞毒剂）和 Cy5 荧光团（MMAE-Cy5-trastuzumab）进行了双重修饰。MMAE-Cy5-trastuzumab 保留了人表皮生长因子受体 2（HER2）识别活性，对 HER2 阳性细胞具有细胞毒性。此外，MMAE-Cy5-曲妥珠单抗还能成功地观察到小鼠肿瘤中的 HER2 阳性癌细胞。这种简单易行的方法将扩大具有明确结构的蛋白质共轭物在广泛研究领域的应用范围。
{"title":"One-Step Maleimide-Based Dual Functionalization of Protein N-Termini","authors":"Kengo Hanaya, Kazuaki Taguchi, Yuki Wada, Masaki Kawano","doi":"10.1002/anie.202417134","DOIUrl":"https://doi.org/10.1002/anie.202417134","url":null,"abstract":"Maleimide derivatives are privileged reagents for chemically modifying proteins through the Michael addition reaction with cysteine due to their selectivity, operational simplicity, and commercial availability. However, since accessible free cysteine is rarely found in natural proteins, it is highly desirable to find alternative targets to enable direct bioconjugation of proteins with maleimides. In this study, we have developed an operationally simple and straightforward method for the N-terminal modification of proteins without the need for mutagenesis via a copper(II)-mediated [3+2] cycloaddition reaction with maleimides and 2-pyridinecarboxaldehyde (2-PCA) derivatives under non-denaturing conditions at pH 6 and 37 °C in aqueous media. Our method utilizes commercially available maleimides to attach diverse functionalities to various N-terminal amino acids. We demonstrate the preparation of a ternary protein complex cross-linked at the N-termini and dually modified trastuzumab equipped with monomethyl auristatin E (MMAE), a cytotoxic agent, and a Cy5 fluorophore (MMAE–Cy5–trastuzumab). MMAE–Cy5–trastuzumab retained human epidermal growth factor receptor 2 (HER2) recognition activity and exerted cytotoxicity against HER2-positive cells. Furthermore, MMAE–Cy5–trastuzumab allowed successful visualization of HER2-positive cancer cells in mouse tumors. This straightforward method will expand the accessibility of protein conjugates with well-defined structures in a wide range of research fields.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"26 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We report a highly diastereoselective protocol for the synthesis of 1,4- and 1,5-dicarbonyl compounds from densely substituted cyclopropanols. The methodology involves a palladium-catalyzed ring opening reaction followed by a “metal-walk” and oxidation of a remote hydroxyl group. The methodology represents a new application of cyclopropanols as initiation sites for chain walking remote functionalization. Importantly, this approach provides a straightforward access to highly valuable succinaldehyde derivatives bearing vicinal quaternary and tertiary stereocenters as single diastereomers.
{"title":"Stereoselective Synthesis of 1,n-Dicarbonyl Compounds Through Palladium-Catalyzed Ring Opening/Isomerization of Densely Substituted Cyclopropanols","authors":"Ilan Marek, Charlotte S. Teschers, Anthony Cohen","doi":"10.1002/anie.202421476","DOIUrl":"https://doi.org/10.1002/anie.202421476","url":null,"abstract":"We report a highly diastereoselective protocol for the synthesis of 1,4- and 1,5-dicarbonyl compounds from densely substituted cyclopropanols. The methodology involves a palladium-catalyzed ring opening reaction followed by a “metal-walk” and oxidation of a remote hydroxyl group. The methodology represents a new application of cyclopropanols as initiation sites for chain walking remote functionalization. Importantly, this approach provides a straightforward access to highly valuable succinaldehyde derivatives bearing vicinal quaternary and tertiary stereocenters as single diastereomers.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"3 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673765","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 oxygen evolution reaction (OER) plays a crucial role in water electrolysis and renewable energy conversion processes. Descriptors are utilized to elucidate the structure-performance relationships of OER catalytic materials, yet each descriptor exhibits specificity to particular systems. Currently, there is a lack of effective descriptors to describe the relationship between electronic structure and OER performance in ionic systems. This study reveals for the first time that widely used OER descriptors, the d-band center and charge transfer energy, are limited in their effectiveness for oxide systems dominated by ionic bonds, in which ionic interactions significantly enhance or suppress the catalytic activity. Furthermore, composite descriptors tailored for ionic systems are proposed, with findings extended to complex multi-component and high-entropy oxides. The results indicate that the metal d-band unoccupied states parameter and the active states parameter can serve as effective OER descriptors for ionic catalytic materials. This work addresses the gap in OER descriptors for ionic systems, offering a new theoretical foundation and guidance for the development of efficient OER catalytic materials.
氧进化反应（OER）在水电解和可再生能源转换过程中起着至关重要的作用。描述符被用来阐明氧进化反应催化材料的结构-性能关系，但每种描述符都对特定系统具有特异性。目前，还缺乏有效的描述符来描述离子体系中电子结构与 OER 性能之间的关系。本研究首次揭示了广泛使用的 OER 描述子（d-带中心和电荷转移能）对于以离子键为主的氧化物体系的有效性是有限的，在这些体系中，离子相互作用会显著增强或抑制催化活性。此外，还提出了针对离子体系的复合描述符，并将研究结果扩展到复杂的多组分和高熵氧化物。结果表明，金属 d 带未占态参数和活性态参数可作为离子催化材料的有效 OER 描述因子。这项研究填补了离子体系 OER 描述因子的空白，为开发高效的 OER 催化材料提供了新的理论基础和指导。
{"title":"Applicable Descriptors under Weak Metal-Oxygen d-p Interaction for the Oxygen Evolution Reaction","authors":"Fangshi Fan, Bohan Lei, Xiaomin Song, Jiayuan Liang, Weiwei Cai, Yu Zhong, Yongjun Wu, Ningzhong Bao, Lingjie Zhang","doi":"10.1002/anie.202419718","DOIUrl":"https://doi.org/10.1002/anie.202419718","url":null,"abstract":"The oxygen evolution reaction (OER) plays a crucial role in water electrolysis and renewable energy conversion processes. Descriptors are utilized to elucidate the structure-performance relationships of OER catalytic materials, yet each descriptor exhibits specificity to particular systems. Currently, there is a lack of effective descriptors to describe the relationship between electronic structure and OER performance in ionic systems. This study reveals for the first time that widely used OER descriptors, the d-band center and charge transfer energy, are limited in their effectiveness for oxide systems dominated by ionic bonds, in which ionic interactions significantly enhance or suppress the catalytic activity. Furthermore, composite descriptors tailored for ionic systems are proposed, with findings extended to complex multi-component and high-entropy oxides. The results indicate that the metal d-band unoccupied states parameter and the active states parameter can serve as effective OER descriptors for ionic catalytic materials. This work addresses the gap in OER descriptors for ionic systems, offering a new theoretical foundation and guidance for the development of efficient OER catalytic materials.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"251 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673798","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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