Yuxiao Wang, Shi-Jun Li, Feng Jiang, Yu Lan, Xiaoming Wang
As one of the most powerful trifluoromethylation reagents, (trifluoromethyl)trimethylsilane (TMSCF3) has been widely used for the synthesis of fluorine-containing molecules. However, to the best of our knowledge, the simultaneous incorporation of both TMS- and CF3- groups of this reagent onto the same carbon of the products has not been realized. Herein, we report an unprecedented SmI2/Sm promoted deoxygenative difunctionalization of amides with TMSCF3, in which both silyl and trifluoromethyl groups are incorporated into the final product, yielding α-silyl-α-trifluoromethyl amines with high efficiency. Notably, the silyl group could be further transformed into other functional groups, providing a new method for the synthesis of α-quaternary α-CF3-amines.
{"title":"Making Full Use of TMSCF<sub>3</sub>: Deoxygenative Trifluoromethylation/Silylation of Amides.","authors":"Yuxiao Wang, Shi-Jun Li, Feng Jiang, Yu Lan, Xiaoming Wang","doi":"10.1021/jacs.4c04760","DOIUrl":"https://doi.org/10.1021/jacs.4c04760","url":null,"abstract":"<p><p>As one of the most powerful trifluoromethylation reagents, (trifluoromethyl)trimethylsilane (TMSCF<sub>3</sub>) has been widely used for the synthesis of fluorine-containing molecules. However, to the best of our knowledge, the simultaneous incorporation of both TMS- and CF<sub>3</sub>- groups of this reagent onto the same carbon of the products has not been realized. Herein, we report an unprecedented SmI<sub>2</sub>/Sm promoted deoxygenative difunctionalization of amides with TMSCF<sub>3</sub>, in which both silyl and trifluoromethyl groups are incorporated into the final product, yielding α-silyl-α-trifluoromethyl amines with high efficiency. Notably, the silyl group could be further transformed into other functional groups, providing a new method for the synthesis of α-quaternary α-CF<sub>3</sub>-amines.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489966","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}
Here, we report a set of new polymerization reactions enabled by the 1,2-regioselective hydro- and silylcupration of enyne-type propargylic electrophiles. Highly regioregular head-to-tail poly(2-butyne-1,4-diyl)s (HT-PBD), bearing either methyl or silylmethyl side chains, are synthesized for the first time. A rapid entry into carbon-rich copolymers with adjustable silicon content is developed via in situ monomer bifurcation. Furthermore, a one-pot polymerization/semireduction sequence is developed to access a cis-poly(butadiene)-derived backbone by a ligand swap on copper hydride species. Interestingly, borocupration, typically exhibiting identical regioselectivity with its hydro- and silyl analogues, seems to proceed in a 3,4-selective manner. Computational studies suggest the possible role of the propargylic leaving group in this selectivity switch. This work presents a new class of regioregular sp-carbon-rich polymers and meanwhile a novel approach to organosilicon materials.
{"title":"Regioselective Condensation Polymerization of Propargylic Electrophiles Enabled by Catalytic Element-Cupration.","authors":"Zheng-Lin Wang, Rong Zhu","doi":"10.1021/jacs.4c05524","DOIUrl":"https://doi.org/10.1021/jacs.4c05524","url":null,"abstract":"<p><p>Here, we report a set of new polymerization reactions enabled by the 1,2-regioselective hydro- and silylcupration of enyne-type propargylic electrophiles. Highly regioregular head-to-tail poly(2-butyne-1,4-diyl)s (HT-PBD), bearing either methyl or silylmethyl side chains, are synthesized for the first time. A rapid entry into carbon-rich copolymers with adjustable silicon content is developed via in situ monomer bifurcation. Furthermore, a one-pot polymerization/semireduction sequence is developed to access a <i>cis</i>-poly(butadiene)-derived backbone by a ligand swap on copper hydride species. Interestingly, borocupration, typically exhibiting identical regioselectivity with its hydro- and silyl analogues, seems to proceed in a 3,4-selective manner. Computational studies suggest the possible role of the propargylic leaving group in this selectivity switch. This work presents a new class of regioregular <i>sp</i>-carbon-rich polymers and meanwhile a novel approach to organosilicon materials.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475426","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}
It has been widely recognized that the pH environment influences the nanobubble dynamics and hydroxide ions adsorbed on the surface may be responsible for the long-term survival of the nanobubbles. However, understanding the distribution of hydronium and hydroxide ions in the vicinity of a bulk nanobubble surface at a microscopic scale and the consequent impact of these ions on the nanobubble behavior remains a challenging endeavor. In this study, we carried out deep potential molecular dynamics simulations to explore the behavior of a nitrogen nanobubble under neutral, acidic, and alkaline conditions and the inherent mechanism, and we also conducted a theoretical thermodynamic and dynamic analysis to address constraints related to simulation duration. Our simulations and theoretical analyses demonstrate a trend of nanobubble dissolution similar to that observed experimentally, emphasizing the limited dissolution of bulk nanobubbles in alkaline conditions, where hydroxide ions tend to reside slightly farther from the nanobubble surface than hydronium ions, forming more stable hydrogen bond networks that shield the nanobubble from dissolution. In acidic conditions, the hydronium ions preferentially accumulating at the nanobubble surface in an orderly manner drive nanobubble dissolution to increase the entropy of the system, and the dissolved nitrogen molecules further strengthen the hydrogen bond networks of systems by providing a hydrophobic environment for hydronium ions, suggesting both entropy and enthalpy effects contribute to the instability of nanobubbles under acidic conditions. These results offer fresh insights into the double-layer distribution of hydroxide and hydronium near the nitrogen-water interface that influences the dynamic behavior of bulk nanobubbles.
{"title":"Hydroxide and Hydronium Ions Modulate the Dynamic Evolution of Nitrogen Nanobubbles in Water.","authors":"Pengchao Zhang, Changsheng Chen, Muye Feng, Chao Sun, Xuefei Xu","doi":"10.1021/jacs.4c06641","DOIUrl":"https://doi.org/10.1021/jacs.4c06641","url":null,"abstract":"<p><p>It has been widely recognized that the pH environment influences the nanobubble dynamics and hydroxide ions adsorbed on the surface may be responsible for the long-term survival of the nanobubbles. However, understanding the distribution of hydronium and hydroxide ions in the vicinity of a bulk nanobubble surface at a microscopic scale and the consequent impact of these ions on the nanobubble behavior remains a challenging endeavor. In this study, we carried out deep potential molecular dynamics simulations to explore the behavior of a nitrogen nanobubble under neutral, acidic, and alkaline conditions and the inherent mechanism, and we also conducted a theoretical thermodynamic and dynamic analysis to address constraints related to simulation duration. Our simulations and theoretical analyses demonstrate a trend of nanobubble dissolution similar to that observed experimentally, emphasizing the limited dissolution of bulk nanobubbles in alkaline conditions, where hydroxide ions tend to reside slightly farther from the nanobubble surface than hydronium ions, forming more stable hydrogen bond networks that shield the nanobubble from dissolution. In acidic conditions, the hydronium ions preferentially accumulating at the nanobubble surface in an orderly manner drive nanobubble dissolution to increase the entropy of the system, and the dissolved nitrogen molecules further strengthen the hydrogen bond networks of systems by providing a hydrophobic environment for hydronium ions, suggesting both entropy and enthalpy effects contribute to the instability of nanobubbles under acidic conditions. These results offer fresh insights into the double-layer distribution of hydroxide and hydronium near the nitrogen-water interface that influences the dynamic behavior of bulk nanobubbles.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464350","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}
Synthesis of interior-functionalized dendritic macromolecules is generally tedious and labor-intensive, which has been a key factor hampering their practical applications. Here, we have revisited this long-standing challenge and devised a modular and convergent platform to synthesize multifunctional dendrons with all-carbon backbones up to four generations via an in situ functionalization strategy. Enabled by the palladium/norbornene cooperative catalysis, different functional groups can be introduced to each generation of dendrons during the dendron growth, making it convenient for systematic comparison of their properties. The utility of this versatile platform is further showcased in the internal-functionalization-dependent properties of dendrons as organogels and aggregation-induced emission materials.
{"title":"Modular Synthetic Platform for Interior-Functionalized Dendritic Macromolecules Enabled by the Palladium/Norbornene Catalysis.","authors":"Shinyoung Choi, Ki-Young Yoon, Guangbin Dong","doi":"10.1021/jacs.4c06090","DOIUrl":"https://doi.org/10.1021/jacs.4c06090","url":null,"abstract":"<p><p>Synthesis of interior-functionalized dendritic macromolecules is generally tedious and labor-intensive, which has been a key factor hampering their practical applications. Here, we have revisited this long-standing challenge and devised a modular and convergent platform to synthesize multifunctional dendrons with all-carbon backbones up to four generations via an <i>in situ</i> functionalization strategy. Enabled by the palladium/norbornene cooperative catalysis, different functional groups can be introduced to each generation of dendrons during the dendron growth, making it convenient for systematic comparison of their properties. The utility of this versatile platform is further showcased in the internal-functionalization-dependent properties of dendrons as organogels and aggregation-induced emission materials.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464354","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}
Ji Han, Haidong Xu, Bin Zhao, Ruigang Sun, Guangrui Chen, Tianyu Wu, Guiyuan Zhong, Yanjing Gao, Song Lin Zhang, Yusuke Yamauchi, Buyuan Guan
Two-dimensional (2D) hierarchically porous metal-organic framework (MOF) nanoarchitectures with tailorable meso-/macropores hold great promise for enhancing mass transfer kinetics, augmenting accessible active sites, and thereby boosting performance in heterogeneous catalysis. However, achieving the general synthesis of 2D free-standing MOF nanosheets with controllable hierarchical porosity and thickness remains a challenging task. Herein, we present an ingenious "hard" emulsion-induced interface super-assembly strategy for preparing 2D hierarchically porous UiO-66-NH2 nanosheets with highly accessible pore channels, tunable meso-/macropore sizes, and adjustable thicknesses. The methodology relies on transforming the geometric shape of oil droplet templates within appropriate oil-in-water emulsions from conventional zero-dimensional (0D) "soft" liquid spheres to 2D "hard" solid sheets below the oil's melting/freezing point. Subsequent surfactant exchange on the surface of 2D "hard" emulsions facilitates the heterogeneous nucleation and interfacial super-assembly of in situ formed mesostructured MOF nanocomposites, serving as structural units, in a loosely packed manner to produce 2D MOF nanosheets with multimodal micro/meso-/macroporous systems. Importantly, this strategy can be extended to prepare other 2D hierarchically porous MOF nanosheets by altering metal-oxo clusters and organic ligands. Benefiting from fast mass transfer and highly accessible Lewis acidic sites, the resultant 2D hierarchically porous UiO-66-NH2 nanosheets deliver a fabulous catalytic yield of approximately 96% on the CO2 cycloaddition of glycidyl-2-methylphenyl ether, far exceeding the yield of approximately 29% achieved using conventional UiO-66-NH2 microporous crystals. This "hard" emulsion-induced interface super-assembly strategy paves a new path toward the rational construction of elaborate 2D nanoarchitecture of hierarchical MOFs with tailored physicochemical properties for diverse potential applications.
{"title":"\"Hard\" Emulsion-Induced Interface Super-Assembly: A General Strategy for Two-Dimensional Hierarchically Porous Metal-Organic Framework Nanoarchitectures.","authors":"Ji Han, Haidong Xu, Bin Zhao, Ruigang Sun, Guangrui Chen, Tianyu Wu, Guiyuan Zhong, Yanjing Gao, Song Lin Zhang, Yusuke Yamauchi, Buyuan Guan","doi":"10.1021/jacs.4c02321","DOIUrl":"https://doi.org/10.1021/jacs.4c02321","url":null,"abstract":"<p><p>Two-dimensional (2D) hierarchically porous metal-organic framework (MOF) nanoarchitectures with tailorable meso-/macropores hold great promise for enhancing mass transfer kinetics, augmenting accessible active sites, and thereby boosting performance in heterogeneous catalysis. However, achieving the general synthesis of 2D free-standing MOF nanosheets with controllable hierarchical porosity and thickness remains a challenging task. Herein, we present an ingenious \"hard\" emulsion-induced interface super-assembly strategy for preparing 2D hierarchically porous UiO-66-NH<sub>2</sub> nanosheets with highly accessible pore channels, tunable meso-/macropore sizes, and adjustable thicknesses. The methodology relies on transforming the geometric shape of oil droplet templates within appropriate oil-in-water emulsions from conventional zero-dimensional (0D) \"soft\" liquid spheres to 2D \"hard\" solid sheets below the oil's melting/freezing point. Subsequent surfactant exchange on the surface of 2D \"hard\" emulsions facilitates the heterogeneous nucleation and interfacial super-assembly of <i>in situ</i> formed mesostructured MOF nanocomposites, serving as structural units, in a loosely packed manner to produce 2D MOF nanosheets with multimodal micro/meso-/macroporous systems. Importantly, this strategy can be extended to prepare other 2D hierarchically porous MOF nanosheets by altering metal-oxo clusters and organic ligands. Benefiting from fast mass transfer and highly accessible Lewis acidic sites, the resultant 2D hierarchically porous UiO-66-NH<sub>2</sub> nanosheets deliver a fabulous catalytic yield of approximately 96% on the CO<sub>2</sub> cycloaddition of glycidyl-2-methylphenyl ether, far exceeding the yield of approximately 29% achieved using conventional UiO-66-NH<sub>2</sub> microporous crystals. This \"hard\" emulsion-induced interface super-assembly strategy paves a new path toward the rational construction of elaborate 2D nanoarchitecture of hierarchical MOFs with tailored physicochemical properties for diverse potential applications.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475419","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}
Rakesh Mukherjee, Aditya Sengar, Javier Cabello-García, Thomas E Ouldridge
Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.
整个自然系统都在使用动力校对来提高分子识别的特异性。在最基本的层面上,动能校对利用化学燃料的供应来驱动识别相互作用失去平衡,使正确目标和错误目标之间的单个自由能差被利用两次或更多次。尽管动能校对在生物学中非常重要,但在分子识别非常重要的合成系统中(如核酸纳米技术),却很少有人尝试采用动能校对。在本文中,我们介绍了一种基于 DNA 链位移的动力学校对模式,表明在模板化二聚反应过程中,DNA 燃料的消耗可用于增强分子识别。然后,我们展示了动力学校对可以从探针反应的初始速率和长期行为两方面提高探针辨别单核苷酸突变的特异性。
{"title":"Kinetic Proofreading Can Enhance Specificity in a Nonenzymatic DNA Strand Displacement Network.","authors":"Rakesh Mukherjee, Aditya Sengar, Javier Cabello-García, Thomas E Ouldridge","doi":"10.1021/jacs.3c14673","DOIUrl":"https://doi.org/10.1021/jacs.3c14673","url":null,"abstract":"<p><p>Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimerization reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleotide mutations, both in terms of the initial rate with which the probe reacts and the long-time behavior.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475422","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}
Bin Lu, Kohei Takahashi, Jian Zhou, Shintaro Nakagawa, Yuta Yamamoto, Takuya Katashima, Naoko Yoshie, Kyoko Nozaki
Crystalline polyethylenes bearing carboxylic acid groups in the main chain were successfully degraded with a Ce catalyst and visible light. The reaction proceeds in a crystalline solid state without swelling in acetonitrile or water at a reaction temperature as low as 60 or 80 °C, employing dioxygen in air as the only stoichiometric reactant with nearly quantitative recovery of carbon atoms. Heterogeneous features of the reaction allowed us to reveal a dynamic morphological change of polymer crystals during the degradation.
利用 Ce 催化剂和可见光成功地降解了主链中含有羧酸基团的结晶聚乙烯。该反应以结晶固态进行,在乙腈或水中无溶胀,反应温度低至 60 或 80 °C,使用空气中的二氧作为唯一的化学反应剂,几乎可定量回收碳原子。反应的异质性特征使我们得以揭示降解过程中聚合物晶体的动态形态变化。
{"title":"Mild Catalytic Degradation of Crystalline Polyethylene Units in a Solid State Assisted by Carboxylic Acid Groups.","authors":"Bin Lu, Kohei Takahashi, Jian Zhou, Shintaro Nakagawa, Yuta Yamamoto, Takuya Katashima, Naoko Yoshie, Kyoko Nozaki","doi":"10.1021/jacs.4c07458","DOIUrl":"https://doi.org/10.1021/jacs.4c07458","url":null,"abstract":"<p><p>Crystalline polyethylenes bearing carboxylic acid groups in the main chain were successfully degraded with a Ce catalyst and visible light. The reaction proceeds in a crystalline solid state without swelling in acetonitrile or water at a reaction temperature as low as 60 or 80 °C, employing dioxygen in air as the only stoichiometric reactant with nearly quantitative recovery of carbon atoms. Heterogeneous features of the reaction allowed us to reveal a dynamic morphological change of polymer crystals during the degradation.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475424","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}
Enantioselective construction of all-carbon quaternary stereocenters has attracted much attention over the past few decades. A variety of catalytic asymmetric methods have been disclosed based on the use of presynthesized complex reagents that impart congested steric hindrance to the reaction center, which generally produce the chiral molecules through forming one C-C bond. The use of readily available reagents that could build two C-C bonds on the same carbonic center with the concomitant assembly of quaternary stereocenters remains challenging. Herein, we disclose a catalytic asymmetric alkyne multifunctionalization reaction using a gold complex and a chiral spiro phosphoric acid (SPA) for synergistic catalysis. In this method, the readily accessible internal alkynes served as the key gold carbene precursors, followed by carbene gem-dialkylation through Mannich-type addition of enolate species or stepwise formal cycloaddition with methylenimines that are derived from 1,3,5-triazinanes in the presence of SPA. The reaction provides practical access to poly-functionalized chiral linear and cyclic ketones that bear two adjacent quaternary stereocenters in generally good yields and excellent enantioselectivities, leading to an essential complement to the asymmetric construction of quaternary stereocenters using readily available materials with high bond formation efficiency.
{"title":"Enantioselective Construction of Quaternary Stereocenters via A Chiral Spiro Phosphoric Acid-Assisted Formal Gold Carbene <i>gem</i>-Dialkylation Reaction.","authors":"Kewei Chen, Su Zhou, Chao Li, Shanliang Dong, Kemiao Hong, Xinfang Xu","doi":"10.1021/jacs.4c04540","DOIUrl":"https://doi.org/10.1021/jacs.4c04540","url":null,"abstract":"<p><p>Enantioselective construction of all-carbon quaternary stereocenters has attracted much attention over the past few decades. A variety of catalytic asymmetric methods have been disclosed based on the use of presynthesized complex reagents that impart congested steric hindrance to the reaction center, which generally produce the chiral molecules through forming one C-C bond. The use of readily available reagents that could build two C-C bonds on the same carbonic center with the concomitant assembly of quaternary stereocenters remains challenging. Herein, we disclose a catalytic asymmetric alkyne multifunctionalization reaction using a gold complex and a chiral spiro phosphoric acid (SPA) for synergistic catalysis. In this method, the readily accessible internal alkynes served as the key gold carbene precursors, followed by carbene <i>gem</i>-dialkylation through Mannich-type addition of enolate species or stepwise formal cycloaddition with methylenimines that are derived from 1,3,5-triazinanes in the presence of SPA. The reaction provides practical access to poly-functionalized chiral linear and cyclic ketones that bear two adjacent quaternary stereocenters in generally good yields and excellent enantioselectivities, leading to an essential complement to the asymmetric construction of quaternary stereocenters using readily available materials with high bond formation efficiency.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475421","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}
Sabine Oldemeyer, Mariafrancesca La Greca, Pit Langner, Karoline-Luisa Lê Công, Ramona Schlesinger, Joachim Heberle
The ability to track minute changes of a single amino acid residue in a cellular environment is causing a paradigm shift in the attempt to fully understand the responses of biomolecules that are highly sensitive to their environment. Detecting early protein dynamics in living cells is crucial to understanding their mechanisms, such as those of photosynthetic proteins. Here, we elucidate the light response of the microbial chloride pump NmHR from the marine bacterium Nonlabens marinus, located in the membrane of living Escherichia coli cells, using nanosecond time-resolved UV/vis and IR absorption spectroscopy over the time range from nanoseconds to seconds. Transient structural changes of the retinal cofactor and the surrounding apoprotein are recorded using light-induced time-resolved UV/vis and IR difference spectroscopy. Of particular note, we have resolved the kinetics of the transient deprotonation of a single cysteine residue during the photocycle of NmHR out of the manifold of molecular vibrations of the cells. These findings are of high general relevance, given the successful development of optogenetic tools from photoreceptors to interfere with enzymatic and neuronal pathways in living organisms using light pulses as a noninvasive trigger.
{"title":"Nanosecond Transient IR Spectroscopy of Halorhodopsin in Living Cells.","authors":"Sabine Oldemeyer, Mariafrancesca La Greca, Pit Langner, Karoline-Luisa Lê Công, Ramona Schlesinger, Joachim Heberle","doi":"10.1021/jacs.4c03891","DOIUrl":"https://doi.org/10.1021/jacs.4c03891","url":null,"abstract":"<p><p>The ability to track minute changes of a single amino acid residue in a cellular environment is causing a paradigm shift in the attempt to fully understand the responses of biomolecules that are highly sensitive to their environment. Detecting early protein dynamics in living cells is crucial to understanding their mechanisms, such as those of photosynthetic proteins. Here, we elucidate the light response of the microbial chloride pump <i>Nm</i>HR from the marine bacterium <i>Nonlabens marinus</i>, located in the membrane of living <i>Escherichia coli</i> cells, using nanosecond time-resolved UV/vis and IR absorption spectroscopy over the time range from nanoseconds to seconds. Transient structural changes of the retinal cofactor and the surrounding apoprotein are recorded using light-induced time-resolved UV/vis and IR difference spectroscopy. Of particular note, we have resolved the kinetics of the transient deprotonation of a single cysteine residue during the photocycle of <i>Nm</i>HR out of the manifold of molecular vibrations of the cells. These findings are of high general relevance, given the successful development of optogenetic tools from photoreceptors to interfere with enzymatic and neuronal pathways in living organisms using light pulses as a noninvasive trigger.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475425","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}
Pragya Adhikari, Guangmin Li, MaryAnn Go, Danielle Mandikian, Hanine Rafidi, Carl Ng, Sagana Anifa, Kevin Johnson, Linda Bao, Hilda Hernandez Barry, Rebecca Rowntree, Nicholas Agard, Cong Wu, Kang-Jye Chou, Donglu Zhang, Katherine R Kozak, Thomas H Pillow, Gail D Lewis, Shang-Fan Yu, C Andrew Boswell, Jack D Sadowsky
Antibody-drug conjugates (ADCs) for the treatment of cancer aim to achieve selective delivery of a cytotoxic payload to tumor cells while sparing normal tissue. In vivo, multiple tumor-dependent and -independent processes act on ADCs and their released payloads to impact tumor-versus-normal delivery, often resulting in a poor therapeutic window. An ADC with a labeled payload would make synchronous correlations between distribution and tissue-specific pharmacological effects possible, empowering preclinical and clinical efforts to improve tumor-selective delivery; however, few methods to label small molecules without destroying their pharmacological activity exist. Herein, we present a bioorthogonal switch approach that allows a radiolabel attached to an ADC payload to be removed tracelessly at will. We exemplify this approach with a potent DNA-damaging agent, the pyrrolobenzodiazepine (PBD) dimer, delivered as an antibody conjugate targeted to lung tumor cells. The radiometal chelating group, DOTA, was attached via a novel trans-cyclooctene (TCO)-caged self-immolative para-aminobenzyl (PAB) linker to the PBD, stably attenuating payload activity and allowing tracking of biodistribution in tumor-bearing mice via SPECT-CT imaging (live) or gamma counting (post-mortem). Following TCO-PAB-DOTA reaction with tetrazines optimized for extra- and intracellular reactivity, the label was removed to reveal the unmodified PBD dimer capable of inducing potent tumor cell killing in vitro and in mouse xenografts. The switchable antibody radio-drug conjugate (ArDC) we describe integrates, but decouples, the two functions of a theranostic given that it can serve as a diagnostic for payload delivery in the labeled state, but can be switched on demand to a therapeutic agent (an ADC).
{"title":"On Demand Bioorthogonal Switching of an Antibody-Conjugated SPECT Probe to a Cytotoxic Payload: from Imaging to Therapy.","authors":"Pragya Adhikari, Guangmin Li, MaryAnn Go, Danielle Mandikian, Hanine Rafidi, Carl Ng, Sagana Anifa, Kevin Johnson, Linda Bao, Hilda Hernandez Barry, Rebecca Rowntree, Nicholas Agard, Cong Wu, Kang-Jye Chou, Donglu Zhang, Katherine R Kozak, Thomas H Pillow, Gail D Lewis, Shang-Fan Yu, C Andrew Boswell, Jack D Sadowsky","doi":"10.1021/jacs.4c03529","DOIUrl":"https://doi.org/10.1021/jacs.4c03529","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) for the treatment of cancer aim to achieve selective delivery of a cytotoxic payload to tumor cells while sparing normal tissue. In vivo, multiple tumor-dependent and -independent processes act on ADCs and their released payloads to impact tumor-versus-normal delivery, often resulting in a poor therapeutic window. An ADC with a labeled payload would make synchronous correlations between distribution and tissue-specific pharmacological effects possible, empowering preclinical and clinical efforts to improve tumor-selective delivery; however, few methods to label small molecules without destroying their pharmacological activity exist. Herein, we present a bioorthogonal switch approach that allows a radiolabel attached to an ADC payload to be removed tracelessly at will. We exemplify this approach with a potent DNA-damaging agent, the pyrrolobenzodiazepine (PBD) dimer, delivered as an antibody conjugate targeted to lung tumor cells. The radiometal chelating group, DOTA, was attached via a novel <i>trans</i>-cyclooctene (TCO)-caged self-immolative <i>para</i>-aminobenzyl (PAB) linker to the PBD, stably attenuating payload activity and allowing tracking of biodistribution in tumor-bearing mice via SPECT-CT imaging (live) or gamma counting (post-mortem). Following TCO-PAB-DOTA reaction with tetrazines optimized for extra- and intracellular reactivity, the label was removed to reveal the unmodified PBD dimer capable of inducing potent tumor cell killing in vitro and in mouse xenografts. The switchable antibody radio-drug conjugate (ArDC) we describe integrates, but decouples, the two functions of a theranostic given that it can serve as a diagnostic for payload delivery in the labeled state, but can be switched on demand to a therapeutic agent (an ADC).</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464360","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}