Glycans cover the cell surface to form the glycocalyx, which governs a myriad of biological phenomena. However, understanding and regulating glycan functions is extremely challenging due to the large number of heterogeneous glycans that engage in intricate interaction networks with diverse biomolecules. Glycocalyx-editing techniques offer potent tools to probe their functions. In this study, we devised a HaloTag-based technique for glycan manipulation, which enables the introduction of chemically synthesized glycans onto a specific protein (protein of interest, POI) and concurrently incorporates fluorescent units to attach homogeneous, well-defined glycans to the fluorescence-labeled POIs. Leveraging this HaloTag-based glycan-display system, we investigated the influence of the interactions between Gal-3 and various N-glycans on protein dynamics. Our analyses revealed that glycosylation modulates the lateral diffusion of the membrane proteins in a structure-dependent manner through interaction with Gal-3, particularly in the context of the Gal-3-induced formation of the glycan network (galectin lattice). Furthermore, N-glycan attachment was also revealed to have a significant impact on the extracellular vesicle-loading of membrane proteins. Notably, our POI-specific glycan introduction does not disrupt intact glycan structures, thereby enabling a functional analysis of glycans in the presence of native glycan networks. This approach complements conventional glycan-editing methods and provides a means for uncovering the molecular underpinnings of glycan functions on the cell surface.
聚糖覆盖细胞表面,形成糖萼,支配着无数的生物现象。然而,由于大量异构聚糖与不同的生物大分子形成错综复杂的相互作用网络,了解和调控聚糖的功能极具挑战性。糖萼编辑技术为探究其功能提供了有力的工具。在这项研究中,我们设计了一种基于 HaloTag 的聚糖操作技术,它能将化学合成的聚糖引入特定蛋白质(感兴趣的蛋白质,POI),同时结合荧光单元将同质、定义明确的聚糖连接到荧光标记的 POI 上。利用这种基于 HaloTag 的聚糖显示系统,我们研究了 Gal-3 与各种 N-聚糖之间的相互作用对蛋白质动态的影响。我们的分析表明,糖基化通过与 Gal-3 的相互作用,特别是在 Gal-3 诱导的聚糖网络(galectin 网格)形成的背景下,以结构依赖的方式调节了膜蛋白的横向扩散。此外,研究还发现,N-聚糖的附着对膜蛋白的细胞外囊载荷也有重大影响。值得注意的是,我们的 POI 特异性聚糖导入不会破坏完整的聚糖结构,因此可以在存在原生聚糖网络的情况下对聚糖进行功能分析。这种方法补充了传统的聚糖编辑方法,为揭示细胞表面聚糖功能的分子基础提供了一种手段。
{"title":"<i>De Novo</i> Glycan Display on Cell Surfaces Using HaloTag: Visualizing the Effect of the Galectin Lattice on the Lateral Diffusion and Extracellular Vesicle Loading of Glycosylated Membrane Proteins.","authors":"Ayane Miura, Yoshiyuki Manabe, Kenichi G N Suzuki, Hiroki Shomura, Soichiro Okamura, Asuka Shirakawa, Kumpei Yano, Shuto Miyake, Koki Mayusumi, Chun-Cheng Lin, Kenta Morimoto, Jojiro Ishitobi, Ikuhiko Nakase, Kenta Arai, Shouhei Kobayashi, Ushio Ishikawa, Hirotaka Kanoh, Eiji Miyoshi, Toshiyuki Yamaji, Kazuya Kabayama, Koichi Fukase","doi":"10.1021/jacs.4c02040","DOIUrl":"https://doi.org/10.1021/jacs.4c02040","url":null,"abstract":"<p><p>Glycans cover the cell surface to form the glycocalyx, which governs a myriad of biological phenomena. However, understanding and regulating glycan functions is extremely challenging due to the large number of heterogeneous glycans that engage in intricate interaction networks with diverse biomolecules. Glycocalyx-editing techniques offer potent tools to probe their functions. In this study, we devised a HaloTag-based technique for glycan manipulation, which enables the introduction of chemically synthesized glycans onto a specific protein (protein of interest, POI) and concurrently incorporates fluorescent units to attach homogeneous, well-defined glycans to the fluorescence-labeled POIs. Leveraging this HaloTag-based glycan-display system, we investigated the influence of the interactions between Gal-3 and various <i>N</i>-glycans on protein dynamics. Our analyses revealed that glycosylation modulates the lateral diffusion of the membrane proteins in a structure-dependent manner through interaction with Gal-3, particularly in the context of the Gal-3-induced formation of the glycan network (galectin lattice). Furthermore, <i>N</i>-glycan attachment was also revealed to have a significant impact on the extracellular vesicle-loading of membrane proteins. Notably, our POI-specific glycan introduction does not disrupt intact glycan structures, thereby enabling a functional analysis of glycans in the presence of native glycan networks. This approach complements conventional glycan-editing methods and provides a means for uncovering the molecular underpinnings of glycan functions on the cell surface.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496267","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}
Songyee Park, Sung-Yun Kang, Sanghee Yang, Tae-Lim Choi
Self-assembly of conjugated polymers offers a powerful method to prepare semiconducting two-dimensional (2D) nanosheets for optoelectronic applications. However, due to the typical biaxial growth behavior of the polymer self-assembly, independent control of the width and length of 2D sheets has been challenging. Herein, we present a greatly accelerated crystallization-driven self-assembly (CDSA) system of polyacetylene-based conjugated polymer to produce 2D semiconducting nanorectangles with precisely controllable dimensions. In detail, rectangular 2D seeds with tunable widths of 0.2-1.3 μm were produced by changing the cosolvent% and grown in the length direction by uniaxial living CDSA up to 11.8 μm. The growth rate was effectively enhanced by tuning the cosolvent%, seed concentration, and temperature, achieving up to 27-fold increase. Additionally, systematic kinetic investigation yielded empirical rate equations, elucidating the relationship between growth rate constant, cosolvent%, seed concentration, and seed width. Finally, the living CDSA allowed us to prepare penta-block comicelles with tunable width, length, and height.
{"title":"Independent Control of the Width and Length of Semiconducting 2D Nanorectangles via Accelerated Living Crystallization-Driven Self-Assembly.","authors":"Songyee Park, Sung-Yun Kang, Sanghee Yang, Tae-Lim Choi","doi":"10.1021/jacs.4c05351","DOIUrl":"https://doi.org/10.1021/jacs.4c05351","url":null,"abstract":"<p><p>Self-assembly of conjugated polymers offers a powerful method to prepare semiconducting two-dimensional (2D) nanosheets for optoelectronic applications. However, due to the typical biaxial growth behavior of the polymer self-assembly, independent control of the width and length of 2D sheets has been challenging. Herein, we present a greatly accelerated crystallization-driven self-assembly (CDSA) system of polyacetylene-based conjugated polymer to produce 2D semiconducting nanorectangles with precisely controllable dimensions. In detail, rectangular 2D seeds with tunable widths of 0.2-1.3 <i>μ</i>m were produced by changing the cosolvent% and grown in the length direction by uniaxial living CDSA up to 11.8 <i>μ</i>m. The growth rate was effectively enhanced by tuning the cosolvent%, seed concentration, and temperature, achieving up to 27-fold increase. Additionally, systematic kinetic investigation yielded empirical rate equations, elucidating the relationship between growth rate constant, cosolvent%, seed concentration, and seed width. Finally, the living CDSA allowed us to prepare penta-block comicelles with tunable width, length, and height.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141532828","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}
Axel Leppert, Jianhui Feng, Vaida Railaite, Tomas Bohn Pessatti, Carmine P Cerrato, Cecilia Mörman, Hannah Osterholz, David P Lane, Filipe R N C Maia, Markus B Linder, Anna Rising, Michael Landreh
Gelation of protein condensates formed by liquid-liquid phase separation occurs in a wide range of biological contexts, from the assembly of biomaterials to the formation of fibrillar aggregates, and is therefore of interest for biomedical applications. Soluble-to-gel (sol-gel) transitions are controlled through macroscopic processes such as changes in temperature or buffer composition, resulting in bulk conversion of liquid droplets into microgels within minutes to hours. Using microscopy and mass spectrometry, we show that condensates of an engineered mini-spidroin (NT2repCTYF) undergo a spontaneous sol-gel transition resulting in the loss of exchange of proteins between the soluble and the condensed phase. This feature enables us to specifically trap a silk-domain-tagged target protein in the spidroin microgels. Surprisingly, laser pulses trigger near-instant gelation. By loading the condensates with fluorescent dyes or drugs, we can control the wavelength at which gelation is triggered. Fluorescence microscopy reveals that laser-induced gelation significantly further increases the partitioning of the fluorescent molecules into the condensates. In summary, our findings demonstrate direct control of phase transitions in individual condensates, opening new avenues for functional and structural characterization.
{"title":"Controlling Drug Partitioning in Individual Protein Condensates through Laser-Induced Microscale Phase Transitions.","authors":"Axel Leppert, Jianhui Feng, Vaida Railaite, Tomas Bohn Pessatti, Carmine P Cerrato, Cecilia Mörman, Hannah Osterholz, David P Lane, Filipe R N C Maia, Markus B Linder, Anna Rising, Michael Landreh","doi":"10.1021/jacs.4c06688","DOIUrl":"https://doi.org/10.1021/jacs.4c06688","url":null,"abstract":"<p><p>Gelation of protein condensates formed by liquid-liquid phase separation occurs in a wide range of biological contexts, from the assembly of biomaterials to the formation of fibrillar aggregates, and is therefore of interest for biomedical applications. Soluble-to-gel (sol-gel) transitions are controlled through macroscopic processes such as changes in temperature or buffer composition, resulting in bulk conversion of liquid droplets into microgels within minutes to hours. Using microscopy and mass spectrometry, we show that condensates of an engineered mini-spidroin (NT2repCT<sup>YF</sup>) undergo a spontaneous sol-gel transition resulting in the loss of exchange of proteins between the soluble and the condensed phase. This feature enables us to specifically trap a silk-domain-tagged target protein in the spidroin microgels. Surprisingly, laser pulses trigger near-instant gelation. By loading the condensates with fluorescent dyes or drugs, we can control the wavelength at which gelation is triggered. Fluorescence microscopy reveals that laser-induced gelation significantly further increases the partitioning of the fluorescent molecules into the condensates. In summary, our findings demonstrate direct control of phase transitions in individual condensates, opening new avenues for functional and structural characterization.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141532824","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}
Tian-Ci Wang, Zheng Zhang, Guodong Rao, Jiedong Li, Josephine Shirah, R David Britt, Qilei Zhu, Yang Yang
Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, the use of well-tailored photoredox catalysts represented the key to enable efficient pyridoxal phosphate (PLP) enzyme-catalyzed radical reactions. Here, we report a PLP-dependent threonine aldolase-catalyzed asymmetric α-C-H alkylation of abundant amino acids using Katritzky pyridinium salts as alkylating agents. The use of engineered threonine aldolases allowed for this redox-neutral radical alkylation to proceed efficiently, giving rise to challenging α-trisubstituted and -tetrasubstituted ncAA products in a protecting-group-free fashion with excellent enantiocontrol. Mechanistically, this enantioselective α-alkylation capitalizes on the unique reactivity of the persistent enzymatic quinonoid intermediate derived from the PLP cofactor and the amino acid substrate to allow for novel radical C-C coupling. Surprisingly, this photobiocatalytic process does not require the use of well-established photoredox catalysts and operates through an unconventional photoinduced radical generation involving a PLP-derived aldimine. The ability to develop photobiocatalytic reactions without relying on classic photocatalysts or photoenzymes opens up new avenues for advancing stereoselective intermolecular radical reactions that are not known in either organic chemistry or enzymology.
{"title":"Threonine Aldolase-Catalyzed Enantioselective α-Alkylation of Amino Acids through Unconventional Photoinduced Radical Initiation.","authors":"Tian-Ci Wang, Zheng Zhang, Guodong Rao, Jiedong Li, Josephine Shirah, R David Britt, Qilei Zhu, Yang Yang","doi":"10.1021/jacs.4c05949","DOIUrl":"https://doi.org/10.1021/jacs.4c05949","url":null,"abstract":"<p><p>Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, the use of well-tailored photoredox catalysts represented the key to enable efficient pyridoxal phosphate (PLP) enzyme-catalyzed radical reactions. Here, we report a PLP-dependent threonine aldolase-catalyzed asymmetric α-C-H alkylation of abundant amino acids using Katritzky pyridinium salts as alkylating agents. The use of engineered threonine aldolases allowed for this redox-neutral radical alkylation to proceed efficiently, giving rise to challenging α-trisubstituted and -tetrasubstituted ncAA products in a protecting-group-free fashion with excellent enantiocontrol. Mechanistically, this enantioselective α-alkylation capitalizes on the unique reactivity of the persistent enzymatic quinonoid intermediate derived from the PLP cofactor and the amino acid substrate to allow for novel radical C-C coupling. Surprisingly, this photobiocatalytic process does not require the use of well-established photoredox catalysts and operates through an unconventional photoinduced radical generation involving a PLP-derived aldimine. The ability to develop photobiocatalytic reactions without relying on classic photocatalysts or photoenzymes opens up new avenues for advancing stereoselective intermolecular radical reactions that are not known in either organic chemistry or enzymology.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496353","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}
Jake J Blackner, Olivia M Schneider, Warren O Wong, Dennis G Hall
The design of small molecules with unique geometric profiles or molecular connectivity represents an intriguing yet neglected challenge in modern organic synthesis. This challenge is compounded when emphasis is placed on the preparation of new chemotypes that have distinct and practical functions. To expand the structural diversity of boron-containing heterocycles, we report herein the preparation of novel monocyclic hemiboronic acids, diazaborines. These compounds have enabled the study of a pseudoaromatic boranol-containing (B-OH) ring free of influence from an appended aromatic system. Synthetic and spectroscopic studies have provided insight into the aromatic character, Lewis acidic nature, chemical reactivity, and unique ability of the exocyclic B-OH unit to participate in hydroxy exchange, suggesting their use in organocatalysis and as reversible covalent inhibitors. Moreover, density functional theory and nucleus-independent chemical shift calculations reveal that the aromatic character of the boroheterocyclic ring is increased significantly in comparison to known bicyclic benzodiazaborines (naphthoid congeners), consequently leading to attenuated Lewis acidity. Direct structural comparison to a well-established biaryl isostere, 2-phenylphenol, through X-ray crystallographic analysis reveals that N-aryl derivatives are strikingly similar in size and conformation, with attenuated logP values underscoring the value of the polar BNN unit. Their potential application as low-molecular-weight scaffolds in drug discovery is demonstrated through orthogonal diversification and preliminary antifungal evaluation (Candida albicans), which unveiled analogs with low micromolar inhibitory concentration.
{"title":"Removing Neighboring Ring Influence in Monocyclic B-OH Diazaborines: Properties and Reactivity as Phenolic Bioisosteres with Dynamic Hydroxy Exchange.","authors":"Jake J Blackner, Olivia M Schneider, Warren O Wong, Dennis G Hall","doi":"10.1021/jacs.4c06360","DOIUrl":"https://doi.org/10.1021/jacs.4c06360","url":null,"abstract":"<p><p>The design of small molecules with unique geometric profiles or molecular connectivity represents an intriguing yet neglected challenge in modern organic synthesis. This challenge is compounded when emphasis is placed on the preparation of new chemotypes that have distinct and practical functions. To expand the structural diversity of boron-containing heterocycles, we report herein the preparation of novel monocyclic hemiboronic acids, diazaborines. These compounds have enabled the study of a pseudoaromatic boranol-containing (B-OH) ring free of influence from an appended aromatic system. Synthetic and spectroscopic studies have provided insight into the aromatic character, Lewis acidic nature, chemical reactivity, and unique ability of the exocyclic B-OH unit to participate in hydroxy exchange, suggesting their use in organocatalysis and as reversible covalent inhibitors. Moreover, density functional theory and nucleus-independent chemical shift calculations reveal that the aromatic character of the boroheterocyclic ring is increased significantly in comparison to known bicyclic benzodiazaborines (naphthoid congeners), consequently leading to attenuated Lewis acidity. Direct structural comparison to a well-established biaryl isostere, 2-phenylphenol, through X-ray crystallographic analysis reveals that <i>N</i>-aryl derivatives are strikingly similar in size and conformation, with attenuated log<i>P</i> values underscoring the value of the polar BNN unit. Their potential application as low-molecular-weight scaffolds in drug discovery is demonstrated through orthogonal diversification and preliminary antifungal evaluation (<i>Candida albicans</i>), which unveiled analogs with low micromolar inhibitory concentration.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489974","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}
Single-molecule junctions, formed by a single molecule bridging a gap between two metal electrodes, are attracting attention as basic models of ultrasmall electronic devices. Although charge transport through π-conjugated molecules with π-delocalized system has been widely studied for a number of molecular junctions, there has been almost no research on charge transport through molecular junctions with a σ-delocalized orbital system. Compounds with hexa-selenium-substituted benzene form a σ-delocalized orbital system on the periphery of the benzene ring. In this study, we fabricated single-molecule junctions with the σ-delocalized orbital systems arising from lone-pair interactions of selenium atoms and clarified their electronic properties using the break-junction method. The single-molecule junctions with the σ-orbital systems show efficient charge transport properties and can be one of the alternatives to those with conventional π-orbital systems as minute electronic conductors.
{"title":"Charge Transport through Single-Molecule Junctions with σ-Delocalized Systems.","authors":"Shintaro Fujii, Saya Seko, Taichi Tanaka, Yuki Yoshihara, Shunsuke Furukawa, Tomoaki Nishino, Masaichi Saito","doi":"10.1021/jacs.4c06732","DOIUrl":"https://doi.org/10.1021/jacs.4c06732","url":null,"abstract":"<p><p>Single-molecule junctions, formed by a single molecule bridging a gap between two metal electrodes, are attracting attention as basic models of ultrasmall electronic devices. Although charge transport through π-conjugated molecules with π-delocalized system has been widely studied for a number of molecular junctions, there has been almost no research on charge transport through molecular junctions with a σ-delocalized orbital system. Compounds with hexa-selenium-substituted benzene form a σ-delocalized orbital system on the periphery of the benzene ring. In this study, we fabricated single-molecule junctions with the σ-delocalized orbital systems arising from lone-pair interactions of selenium atoms and clarified their electronic properties using the break-junction method. The single-molecule junctions with the σ-orbital systems show efficient charge transport properties and can be one of the alternatives to those with conventional π-orbital systems as minute electronic conductors.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489960","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}
Pavel Savchenko, Din Zelikovich, Hadassah Elgavi Sinai, Roi Baer, Daniel Mandler
Engineered metallic nanoparticles, which are found in numerous applications, are usually stabilized by organic ligands influencing their interfacial properties. We found that the ligands affect tremendously the electrochemical peak oxidation potentials of the nanoparticles. In this work, identical gold nanoparticles were ligand-exchanged and carefully analyzed to enable a precise and highly reproducible comparison. The peak potential difference between gold nanoparticles stabilized by various ligands, such as 2- and 4-mercaptobenzoic acid, can be as high as 71 mV, which is substantial in energetic terms. A detailed study supported by density functional theory (DFT) calculations aimed to determine the source of this interesting effect. The DFT simulations of the ligand adsorption modes on Au surfaces were used to calculate the redox potentials through the thermodynamic cycle method. The DFT results of the peak potential shift were in good agreement with the experimental results for a few ligands, but showed some discrepancy, which was attributed to kinetic effects. The kinetic rate constant of the oxidation of Au nanoparticles stabilized by 4-mercaptobenzoic acid was found to be twice as large as that of the Au nanoparticles stabilized by citrate, as calculated from Laviron's theory and the Tafel equation. Finally, these findings could be applied to some novel applications such as determining the distribution of nanoparticle population in a dispersion as well as monitoring the ligand exchange between nanoparticles.
{"title":"The Effect of the Capping Agents of Nanoparticles on Their Redox Potential.","authors":"Pavel Savchenko, Din Zelikovich, Hadassah Elgavi Sinai, Roi Baer, Daniel Mandler","doi":"10.1021/jacs.4c02524","DOIUrl":"https://doi.org/10.1021/jacs.4c02524","url":null,"abstract":"<p><p>Engineered metallic nanoparticles, which are found in numerous applications, are usually stabilized by organic ligands influencing their interfacial properties. We found that the ligands affect tremendously the electrochemical peak oxidation potentials of the nanoparticles. In this work, identical gold nanoparticles were ligand-exchanged and carefully analyzed to enable a precise and highly reproducible comparison. The peak potential difference between gold nanoparticles stabilized by various ligands, such as 2- and 4-mercaptobenzoic acid, can be as high as 71 mV, which is substantial in energetic terms. A detailed study supported by density functional theory (DFT) calculations aimed to determine the source of this interesting effect. The DFT simulations of the ligand adsorption modes on Au surfaces were used to calculate the redox potentials through the thermodynamic cycle method. The DFT results of the peak potential shift were in good agreement with the experimental results for a few ligands, but showed some discrepancy, which was attributed to kinetic effects. The kinetic rate constant of the oxidation of Au nanoparticles stabilized by 4-mercaptobenzoic acid was found to be twice as large as that of the Au nanoparticles stabilized by citrate, as calculated from Laviron's theory and the Tafel equation. Finally, these findings could be applied to some novel applications such as determining the distribution of nanoparticle population in a dispersion as well as monitoring the ligand exchange between nanoparticles.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496292","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}
Anna L. Dunn*, Debbie M. Decker*, Kirk Hunter, Ann Kimble-Hill, Jennifer L. Maclachlan and Catherine Situma,
{"title":"“How Can I Help?” How Safety Professionals and Institutional Leaders Can Promote Laboratory Safety through Diversity, Equity, Inclusion, and Respect","authors":"Anna L. Dunn*, Debbie M. Decker*, Kirk Hunter, Ann Kimble-Hill, Jennifer L. Maclachlan and Catherine Situma, ","doi":"10.1021/jacs.4c04829","DOIUrl":"10.1021/jacs.4c04829","url":null,"abstract":"","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489985","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}
Two limiting mechanisms are possible for oxidative addition of (hetero)aryl (pseudo)halides at Pd(0): a 3-centered concerted and a nucleophilic displacement mechanism. Until now, there has been little understanding about when each mechanism is relevant. Prior investigations to distinguish between these pathways were limited to a few specific combinations of the substrate and ligand. Here, we computationally evaluated over 180 transition structures for oxidative addition in order to determine mechanistic trends based on substrate, ligand(s), and coordination number. Natural abundance 13C kinetic isotope effects provide experimental results consistent with computational predictions. Key findings include that (1) differences in highest occupied molecular orbital (HOMO) symmetries dictate that, although 12e- PdL is strongly biased toward a 3-centered concerted mechanism, 14e- PdL2 often prefers a nucleophilic displacement mechanism; (2) ligand electronics and sterics, including ligand bite angle, influence the preferred mechanism of the reaction at PdL2; (3) phenyl triflate always reacts through a displacement mechanism regardless of the catalyst structure due to the stability of a triflate anion and the inability of oxygen to effectively donate electron density to Pd; and (4) the high reactivity of C-X bonds adjacent to nitrogen in pyridine substrates relates to stereoelectronic stabilization of a nucleophilic displacement transition state. This work has implications for controlling rate and selectivity in catalytic couplings, and we demonstrate application of the mechanistic insight toward chemodivergent cross-couplings of bromochloroheteroarenes.
{"title":"Oxidative Addition of (Hetero)aryl (Pseudo)halides at Palladium(0): Origin and Significance of Divergent Mechanisms.","authors":"Matthew J Kania, Albert Reyes, Sharon R Neufeldt","doi":"10.1021/jacs.4c04496","DOIUrl":"https://doi.org/10.1021/jacs.4c04496","url":null,"abstract":"<p><p>Two limiting mechanisms are possible for oxidative addition of (hetero)aryl (pseudo)halides at Pd(0): a 3-centered concerted and a nucleophilic displacement mechanism. Until now, there has been little understanding about when each mechanism is relevant. Prior investigations to distinguish between these pathways were limited to a few specific combinations of the substrate and ligand. Here, we computationally evaluated over 180 transition structures for oxidative addition in order to determine mechanistic trends based on substrate, ligand(s), and coordination number. Natural abundance <sup>13</sup>C kinetic isotope effects provide experimental results consistent with computational predictions. Key findings include that (1) differences in highest occupied molecular orbital (HOMO) symmetries dictate that, although 12e<sup>-</sup> PdL is strongly biased toward a 3-centered concerted mechanism, 14e<sup>-</sup> PdL<sub>2</sub> often prefers a nucleophilic displacement mechanism; (2) ligand electronics and sterics, including ligand bite angle, influence the preferred mechanism of the reaction at PdL<sub>2</sub>; (3) phenyl triflate always reacts through a displacement mechanism regardless of the catalyst structure due to the stability of a triflate anion and the inability of oxygen to effectively donate electron density to Pd; and (4) the high reactivity of C-X bonds adjacent to nitrogen in pyridine substrates relates to stereoelectronic stabilization of a nucleophilic displacement transition state. This work has implications for controlling rate and selectivity in catalytic couplings, and we demonstrate application of the mechanistic insight toward chemodivergent cross-couplings of bromochloroheteroarenes.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metal radicals have shown versatile reactivity in modern synthetic chemistry. However, the use of zinc radicals for molecular synthesis has been barely explored. Here, we show that a transient zinc radical can be formed through photoactivation of a zinc-zinc bonded compound, which is able to mediate the selective dimerization of alkenes and allenes. Treatment of dizinc compounds [L2Zn2] [L = CH3C(2,6-iPr2C6H3N)CHC(CH3)(NCH2CH2PR2); R = Ph (LPh) or iPr (LiPr)] with a diverse array of aromatic alkenes under UV irradiation (365 nm) facilely afforded the head-to-head coupling products, i.e., 1,4-dizinciobutanes in high yields. In addition, arylallenes could also be selectively dimerized by the dizinc compound to give 2,5-dizincyl-functionalized 1,5-hexadienes under the same conditions. Control reactions of [LPh2Zn2] in the presence of UV irradiation isolated a zinc phenyl complex and a trimeric zinc phosphide complex resulting from C-P bond cleavage at the tridentate ligand. Reactions of photoactivated dizinc compounds with organic spin traps, i.e., 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and 2,2'-bipyridine (2,2'-bpy), successfully isolated zinc radical trapping products [LZnOTEMP] and [LPhZn(2,2'-bpy)·-], respectively. The profile of alkene dimerization was elucidated by density functional theory calculations, which confirmed that a transient zinc radical [LZn·] was initially generated through homolytic Zn-Zn bond cleavage via photoactivation followed by single-electron transfer and radical dimerization. The unique selectivity of the current reaction was also studied computationally.
{"title":"Reductive Dimerization of Alkenes and Allenes Enabled by Photochemically Activated Zinc-Zinc Bonded Compounds.","authors":"Shuilian Xu, Qiujie Wang, Thayalan Rajeshkumar, Shengjie Jiang, Laurent Maron, Xin Xu","doi":"10.1021/jacs.4c07390","DOIUrl":"https://doi.org/10.1021/jacs.4c07390","url":null,"abstract":"<p><p>Metal radicals have shown versatile reactivity in modern synthetic chemistry. However, the use of zinc radicals for molecular synthesis has been barely explored. Here, we show that a transient zinc radical can be formed through photoactivation of a zinc-zinc bonded compound, which is able to mediate the selective dimerization of alkenes and allenes. Treatment of dizinc compounds [<b>L</b><sub>2</sub>Zn<sub>2</sub>] [<b>L</b> = CH<sub>3</sub>C(2,6-<sup><i>i</i></sup>Pr<sub>2</sub>C<sub>6</sub>H<sub>3</sub>N)CHC(CH<sub>3</sub>)(NCH<sub>2</sub>CH<sub>2</sub>PR<sub>2</sub>); R = Ph (<b>L</b><sup>Ph</sup>) or <sup><i>i</i></sup>Pr (<b>L</b><sup><i>i</i>Pr</sup>)] with a diverse array of aromatic alkenes under UV irradiation (365 nm) facilely afforded the head-to-head coupling products, i.e., 1,4-dizinciobutanes in high yields. In addition, arylallenes could also be selectively dimerized by the dizinc compound to give 2,5-dizincyl-functionalized 1,5-hexadienes under the same conditions. Control reactions of [<b>L</b><sup>Ph</sup><sub>2</sub>Zn<sub>2</sub>] in the presence of UV irradiation isolated a zinc phenyl complex and a trimeric zinc phosphide complex resulting from C-P bond cleavage at the tridentate ligand. Reactions of photoactivated dizinc compounds with organic spin traps, i.e., 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and 2,2'-bipyridine (2,2'-bpy), successfully isolated zinc radical trapping products [<b>L</b>ZnOTEMP] and [<b>L</b><sup>Ph</sup>Zn(2,2'-bpy)<sup>·<b>-</b></sup>], respectively. The profile of alkene dimerization was elucidated by density functional theory calculations, which confirmed that a transient zinc radical [<b>L</b>Zn·] was initially generated through homolytic Zn-Zn bond cleavage via photoactivation followed by single-electron transfer and radical dimerization. The unique selectivity of the current reaction was also studied computationally.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489973","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}