Hydrogen sulfide (H2S) is a gaseous signaling molecule, exerting crucial regulatory functions in organelles and cellular environments. H2S exhibits high therapeutic potential and synergistic effects with other drugs, and its potency is notably enhanced through organelle-specific targeting. Yet, the navigation of light-activated H2S donors to specific organelles remains absent. Here, we report the first organelle-specific photocage that simultaneously delivers H2S and a payload with subcellular precision to mitochondria of live human cells using tissue-penetrating near-infrared light as a trigger. The fluorogenic payload enables real-time monitoring of the process, and we demonstrate the concurrent uncaging in mitochondria through a combination of fluorescence microscopy and mitochondria-specific fluorescent probes. We anticipate that these photocages will permit the precise delivery of H2S-drug combinations with exceptional spatiotemporal control, thereby driving the harnessing of known synergistic effects and the discovery of novel therapeutic strategies.
{"title":"Concurrent Subcellular Delivery of Hydrogen Sulfide and a Payload with Near-Infrared Light","authors":"Katarzyna Hanc, Hana Janeková, Peter Štacko","doi":"10.1021/jacsau.4c00445","DOIUrl":"https://doi.org/10.1021/jacsau.4c00445","url":null,"abstract":"Hydrogen sulfide (H<sub>2</sub>S) is a gaseous signaling molecule, exerting crucial regulatory functions in organelles and cellular environments. H<sub>2</sub>S exhibits high therapeutic potential and synergistic effects with other drugs, and its potency is notably enhanced through organelle-specific targeting. Yet, the navigation of light-activated H<sub>2</sub>S donors to specific organelles remains absent. Here, we report the first organelle-specific photocage that simultaneously delivers H<sub>2</sub>S and a payload with subcellular precision to mitochondria of live human cells using tissue-penetrating near-infrared light as a trigger. The fluorogenic payload enables real-time monitoring of the process, and we demonstrate the concurrent uncaging in mitochondria through a combination of fluorescence microscopy and mitochondria-specific fluorescent probes. We anticipate that these photocages will permit the precise delivery of H<sub>2</sub>S-drug combinations with exceptional spatiotemporal control, thereby driving the harnessing of known synergistic effects and the discovery of novel therapeutic strategies.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter T. Beernink, Cristina Di Carluccio, Roberta Marchetti, Linda Cerofolini, Sara Carillo, Alessandro Cangiano, Nathan Cowieson, Jonathan Bones, Antonio Molinaro, Luigi Paduano, Marco Fragai, Benjamin P. Beernink, Sunita Gulati, Jutamas Shaughnessy, Peter A. Rice, Sanjay Ram, Alba Silipo
The spread of multidrug-resistant strains of Neisseria gonorrhoeae, the etiologic agent of gonorrhea, represents a global health emergency. Therefore, the development of a safe and effective vaccine against gonorrhea is urgently needed. In previous studies, murine monoclonal antibody (mAb) 2C7 was raised against gonococcal lipooligosaccharide (LOS). mAb 2C7 elicits complement-dependent bactericidal activity against gonococci, and its glycan epitope is expressed by almost every clinical isolate. Furthermore, we identified a peptide, cyclic peptide 2 (CP2) that mimicked the 2C7 LOS epitope, elicited bactericidal antibodies in mice, and actively protected in a mouse vaginal colonization model. In this study, we performed structural analyses of mAb 2C7 and its complex with the CP2 peptide by X-ray crystallography, NMR spectroscopy, and molecular dynamics (MD) simulations. The crystal structure of Fab 2C7 bound to CP2 showed that the peptide adopted a beta-hairpin conformation and bound the Fab primarily through hydrophobic interactions. We employed NMR spectroscopy and MD simulations to map the 2C7 epitope and identify the bioactive conformation of CP2. We also used small-angle X-ray scattering (SAXS) and native mass spectrometry to obtain further information about the shape and assembly state of the complex. Collectively, our new structural information suggests strategies for humanizing mAb 2C7 as a therapeutic against gonococcal infection and for optimizing peptide CP2 as a vaccine antigen.
淋病的病原体--淋病奈瑟菌的耐多药菌株的传播是一个全球性的健康问题。因此，开发安全有效的淋病疫苗迫在眉睫。在之前的研究中，我们针对淋球菌脂寡糖（LOS）制备了小鼠单克隆抗体（mAb）2C7，mAb 2C7 对淋球菌具有补体依赖性杀菌活性，而且几乎所有临床分离株都表达了它的糖表位。此外，我们还发现了一种模仿 2C7 LOS 表位的多肽--环肽 2（CP2），它能在小鼠体内激发杀菌抗体，并在小鼠阴道定植模型中发挥积极的保护作用。在这项研究中，我们通过 X 射线晶体学、核磁共振光谱和分子动力学（MD）模拟，对 mAb 2C7 及其与 CP2 肽的复合物进行了结构分析。Fab 2C7 与 CP2 结合的晶体结构显示，CP2 肽采用 beta 发夹构象，主要通过疏水相互作用与 Fab 结合。我们利用核磁共振光谱和 MD 模拟绘制了 2C7 表位图，并确定了 CP2 的生物活性构象。我们还利用小角 X 射线散射（SAXS）和原生质谱获得了有关复合物形状和组装状态的更多信息。总之，我们的新结构信息为将 mAb 2C7 人源化为淋球菌感染的治疗药物以及将多肽 CP2 优化为疫苗抗原提供了策略建议。
{"title":"Gonococcal Mimitope Vaccine Candidate Forms a Beta-Hairpin Turn and Binds Hydrophobically to a Therapeutic Monoclonal Antibody","authors":"Peter T. Beernink, Cristina Di Carluccio, Roberta Marchetti, Linda Cerofolini, Sara Carillo, Alessandro Cangiano, Nathan Cowieson, Jonathan Bones, Antonio Molinaro, Luigi Paduano, Marco Fragai, Benjamin P. Beernink, Sunita Gulati, Jutamas Shaughnessy, Peter A. Rice, Sanjay Ram, Alba Silipo","doi":"10.1021/jacsau.4c00359","DOIUrl":"https://doi.org/10.1021/jacsau.4c00359","url":null,"abstract":"The spread of multidrug-resistant strains of <i>Neisseria gonorrhoeae</i>, the etiologic agent of gonorrhea, represents a global health emergency. Therefore, the development of a safe and effective vaccine against gonorrhea is urgently needed. In previous studies, murine monoclonal antibody (mAb) 2C7 was raised against gonococcal lipooligosaccharide (LOS). mAb 2C7 elicits complement-dependent bactericidal activity against gonococci, and its glycan epitope is expressed by almost every clinical isolate. Furthermore, we identified a peptide, cyclic peptide 2 (CP2) that mimicked the 2C7 LOS epitope, elicited bactericidal antibodies in mice, and actively protected in a mouse vaginal colonization model. In this study, we performed structural analyses of mAb 2C7 and its complex with the CP2 peptide by X-ray crystallography, NMR spectroscopy, and molecular dynamics (MD) simulations. The crystal structure of Fab 2C7 bound to CP2 showed that the peptide adopted a beta-hairpin conformation and bound the Fab primarily through hydrophobic interactions. We employed NMR spectroscopy and MD simulations to map the 2C7 epitope and identify the bioactive conformation of CP2. We also used small-angle X-ray scattering (SAXS) and native mass spectrometry to obtain further information about the shape and assembly state of the complex. Collectively, our new structural information suggests strategies for humanizing mAb 2C7 as a therapeutic against gonococcal infection and for optimizing peptide CP2 as a vaccine antigen.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benjamin L. L. Réant, Fraser J. Mackintosh, Gemma K. Gransbury, Carlo Andrea Mattei, Barak Alnami, Benjamin E. Atkinson, Katherine L. Bonham, Jack Baldwin, Ashley J. Wooles, Iñigo J. Vitorica-Yrezabal, Daniel Lee, Nicholas F. Chilton, Stephen T. Liddle, David P. Mills
The paramagnetism of f-block ions has been exploited in chiral shift reagents and magnetic resonance imaging, but these applications tend to focus on 1H NMR shifts as paramagnetic broadening makes less sensitive nuclei more difficult to study. Here we report a solution and solid-state (ss) 29Si NMR study of an isostructural series of locally D3h-symmetric early f-block metal(III) tris-hypersilanide complexes, [M{Si(SiMe3)3}3(THF)2] (1-M; M = La, Ce, Pr, Nd, U); 1-M were also characterized by single crystal and powder X-ray diffraction, EPR, ATR-IR, and UV–vis–NIR spectroscopies, SQUID magnetometry, and elemental analysis. Only one SiMe3 signal was observed in the 29Si ssNMR spectra of 1-M, while two SiMe3 signals were seen in solution 29Si NMR spectra of 1-La and 1-Ce. This is attributed to dynamic averaging of the SiMe3 groups in 1-M in the solid state due to free rotation of the M–Si bonds and dissociation of THF from 1-M in solution to give the locally C3v-symmetric complexes [M{Si(SiMe3)3}3(THF)n] (n = 0 or 1), which show restricted rotation of M–Si bonds on the NMR time scale. Density functional theory and complete active space self-consistent field spin–orbit calculations were performed on 1-M and desolvated solution species to model paramagnetic NMR shifts. We find excellent agreement of experimental 29Si NMR data for diamagnetic 1-La, suggesting n = 1 in solution and reasonable agreement of calculated paramagnetic shifts of SiMe3 groups for 1-M (M = Pr and Nd); the NMR shifts for metal-bound 29Si nuclei could only be reproduced for diamagnetic 1-La, showing the current limitations of pNMR calculations for larger nuclei.
{"title":"Tris-Silanide f-Block Complexes: Insights into Paramagnetic Influence on NMR Chemical Shifts","authors":"Benjamin L. L. Réant, Fraser J. Mackintosh, Gemma K. Gransbury, Carlo Andrea Mattei, Barak Alnami, Benjamin E. Atkinson, Katherine L. Bonham, Jack Baldwin, Ashley J. Wooles, Iñigo J. Vitorica-Yrezabal, Daniel Lee, Nicholas F. Chilton, Stephen T. Liddle, David P. Mills","doi":"10.1021/jacsau.4c00466","DOIUrl":"https://doi.org/10.1021/jacsau.4c00466","url":null,"abstract":"The paramagnetism of f-block ions has been exploited in chiral shift reagents and magnetic resonance imaging, but these applications tend to focus on <sup>1</sup>H NMR shifts as paramagnetic broadening makes less sensitive nuclei more difficult to study. Here we report a solution and solid-state (ss) <sup>29</sup>Si NMR study of an isostructural series of locally <i>D</i><sub>3<i>h</i></sub>-symmetric early f-block metal(III) <i>tris</i>-hypersilanide complexes, [M{Si(SiMe<sub>3</sub>)<sub>3</sub>}<sub>3</sub>(THF)<sub>2</sub>] (<b>1-M</b>; M = La, Ce, Pr, Nd, U); <b>1-M</b> were also characterized by single crystal and powder X-ray diffraction, EPR, ATR-IR, and UV–vis–NIR spectroscopies, SQUID magnetometry, and elemental analysis. Only one SiMe<sub>3</sub> signal was observed in the <sup>29</sup>Si ssNMR spectra of <b>1-M</b>, while two SiMe<sub>3</sub> signals were seen in solution <sup>29</sup>Si NMR spectra of <b>1-La</b> and <b>1-Ce</b>. This is attributed to dynamic averaging of the SiMe<sub>3</sub> groups in <b>1-M</b> in the solid state due to free rotation of the M–Si bonds and dissociation of THF from <b>1-M</b> in solution to give the locally <i>C</i><sub>3<i>v</i></sub>-symmetric complexes [M{Si(SiMe<sub>3</sub>)<sub>3</sub>}<sub>3</sub>(THF)<sub><i>n</i></sub>] (<i>n</i> = 0 or 1), which show restricted rotation of M–Si bonds on the NMR time scale. Density functional theory and complete active space self-consistent field spin–orbit calculations were performed on <b>1-M</b> and desolvated solution species to model paramagnetic NMR shifts. We find excellent agreement of experimental <sup>29</sup>Si NMR data for diamagnetic <b>1-La</b>, suggesting <i>n</i> = 1 in solution and reasonable agreement of calculated paramagnetic shifts of SiMe<sub>3</sub> groups for <b>1-M</b> (M = Pr and Nd); the NMR shifts for metal-bound <sup>29</sup>Si nuclei could only be reproduced for diamagnetic <b>1-La</b>, showing the current limitations of pNMR calculations for larger nuclei.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chun-Yuan Lo, Kelsey P. Koutsoukos, Dan My Nguyen, Yuhang Wu, David Alejandro Angel Trujillo, Tabitha Miller, Tulaja Shrestha, Ethan Mackey, Vidhika S. Damani, Uddhav Kanbur, Robert Opila, David C. Martin, David Kaphan, Laure V. Kayser
The accumulation of plastic waste in the environment is a growing environmental, economic, and societal challenge. Plastic upgrading, the conversion of low-value polymers to high-value materials, could address this challenge. Among upgrading strategies, the sulfonation of aromatic polymers is a powerful approach to access high-value materials for a range of applications, such as ion-exchange resins and membranes, electronic materials, and pharmaceuticals. While many sulfonation methods have been reported, achieving high degrees of sulfonation while minimizing side reactions that lead to defects in the polymer chains remains challenging. Additionally, sulfonating agents are most often used in large excess, which prevents precise control over the degree of sulfonation of aromatic polymers and their functionality. Herein, we address these challenges using 1,3-disulfonic acid imidazolium chloride ([Dsim]Cl), a sulfonic acid-based ionic liquid, to sulfonate aromatic polymers and upgrade plastic waste to electronic materials. We show that stoichiometric [Dsim]Cl can effectively sulfonate model polystyrene up to 92% in high yields, with minimal defects and high regioselectivity for the para position. Owing to its high reactivity, the use of substoichiometric [Dsim]Cl uniquely allows for precise control over the degree of sulfonation of polystyrene. This approach is also applicable to a wide range of aromatic polymers, including waste plastic. To prove the utility of our approach, samples of poly(styrene sulfonate) (PSS), obtained from either partially sulfonated polystyrene or expanded polystyrene waste, are used as scaffolds for poly(3,4-ethylenedioxythiophene) (PEDOT) to form the ubiquitous conductive material PEDOT:PSS. PEDOT:PSS from plastic waste is subsequently integrated into organic electrochemical transistors (OECTs) or as a hole transport layer (HTL) in a hybrid solar cell and shows the same performance as commercial PEDOT:PSS. This imidazolium-mediated approach to precisely sulfonating aromatic polymers provides a pathway toward upgrading postconsumer plastic waste to high-value electronic materials.
{"title":"Imidazolium-Based Sulfonating Agent to Control the Degree of Sulfonation of Aromatic Polymers and Enable Plastics-to-Electronics Upgrading","authors":"Chun-Yuan Lo, Kelsey P. Koutsoukos, Dan My Nguyen, Yuhang Wu, David Alejandro Angel Trujillo, Tabitha Miller, Tulaja Shrestha, Ethan Mackey, Vidhika S. Damani, Uddhav Kanbur, Robert Opila, David C. Martin, David Kaphan, Laure V. Kayser","doi":"10.1021/jacsau.4c00355","DOIUrl":"https://doi.org/10.1021/jacsau.4c00355","url":null,"abstract":"The accumulation of plastic waste in the environment is a growing environmental, economic, and societal challenge. Plastic upgrading, the conversion of low-value polymers to high-value materials, could address this challenge. Among upgrading strategies, the sulfonation of aromatic polymers is a powerful approach to access high-value materials for a range of applications, such as ion-exchange resins and membranes, electronic materials, and pharmaceuticals. While many sulfonation methods have been reported, achieving high degrees of sulfonation while minimizing side reactions that lead to defects in the polymer chains remains challenging. Additionally, sulfonating agents are most often used in large excess, which prevents precise control over the degree of sulfonation of aromatic polymers and their functionality. Herein, we address these challenges using 1,3-disulfonic acid imidazolium chloride ([Dsim]Cl), a sulfonic acid-based ionic liquid, to sulfonate aromatic polymers and upgrade plastic waste to electronic materials. We show that stoichiometric [Dsim]Cl can effectively sulfonate model polystyrene up to 92% in high yields, with minimal defects and high regioselectivity for the <i>para</i> position. Owing to its high reactivity, the use of substoichiometric [Dsim]Cl uniquely allows for precise control over the degree of sulfonation of polystyrene. This approach is also applicable to a wide range of aromatic polymers, including waste plastic. To prove the utility of our approach, samples of poly(styrene sulfonate) (PSS), obtained from either partially sulfonated polystyrene or expanded polystyrene waste, are used as scaffolds for poly(3,4-ethylenedioxythiophene) (PEDOT) to form the ubiquitous conductive material PEDOT:PSS. PEDOT:PSS from plastic waste is subsequently integrated into organic electrochemical transistors (OECTs) or as a hole transport layer (HTL) in a hybrid solar cell and shows the same performance as commercial PEDOT:PSS. This imidazolium-mediated approach to precisely sulfonating aromatic polymers provides a pathway toward upgrading postconsumer plastic waste to high-value electronic materials.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"203 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141520609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Zeng, Zhehao Jin, Shuangjia Zheng, Tao Yu, Ruibo Wu
Illuminating synthetic pathways is essential for producing valuable chemicals, such as bioactive molecules. Chemical and biological syntheses are crucial, and their integration often leads to more efficient and sustainable pathways. Despite the rapid development of retrosynthesis models, few of them consider both chemical and biological syntheses, hindering the pathway design for high-value chemicals. Here, we propose BioNavi by innovating multitask learning and reaction templates into the deep learning-driven model to design hybrid synthesis pathways in a more interpretable manner. BioNavi outperforms existing approaches on different data sets, achieving a 75% hit rate in replicating reported biosynthetic pathways and displaying superior ability in designing hybrid synthesis pathways. Additional case studies further illustrate the potential application of BioNavi in a de novo pathway design. The enhanced web server (http://biopathnavi.qmclab.com/bionavi/) simplifies input operations and implements step-by-step exploration according to user experience. We show that BioNavi is a handy navigator for designing synthetic pathways for various chemicals.
{"title":"Developing BioNavi for Hybrid Retrosynthesis Planning","authors":"Tao Zeng, Zhehao Jin, Shuangjia Zheng, Tao Yu, Ruibo Wu","doi":"10.1021/jacsau.4c00228","DOIUrl":"https://doi.org/10.1021/jacsau.4c00228","url":null,"abstract":"Illuminating synthetic pathways is essential for producing valuable chemicals, such as bioactive molecules. Chemical and biological syntheses are crucial, and their integration often leads to more efficient and sustainable pathways. Despite the rapid development of retrosynthesis models, few of them consider both chemical and biological syntheses, hindering the pathway design for high-value chemicals. Here, we propose BioNavi by innovating multitask learning and reaction templates into the deep learning-driven model to design hybrid synthesis pathways in a more interpretable manner. BioNavi outperforms existing approaches on different data sets, achieving a 75% hit rate in replicating reported biosynthetic pathways and displaying superior ability in designing hybrid synthesis pathways. Additional case studies further illustrate the potential application of BioNavi in a de novo pathway design. The enhanced web server (http://biopathnavi.qmclab.com/bionavi/) simplifies input operations and implements step-by-step exploration according to user experience. We show that BioNavi is a handy navigator for designing synthetic pathways for various chemicals.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141520608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xidan Wen, Chao Zhang, Yuyang Tian, Yinxing Miao, Shaohai Liu, Jing-Juan Xu, Deju Ye, Jian He
Enzymatic molecular in situ self-assembly (E-MISA) that enables the synthesis of high-order nanostructures from synthetic small molecules inside a living subject has emerged as a promising strategy for molecular imaging and theranostics. This strategy leverages the catalytic activity of an enzyme to trigger probe substrate conversion and assembly in situ, permitting prolonging retention and congregating many molecules of probes in the targeted cells or tissues. Enhanced imaging signals or therapeutic functions can be achieved by responding to a specific enzyme. This E-MISA strategy has been successfully applied for the development of enzyme-activated smart molecular imaging or theranostic probes for in vivo applications. In this Perspective, we discuss the general principle of controlling in situ self-assembly of synthetic small molecules by an enzyme and then discuss the applications for the construction of “smart” imaging and theranostic probes against cancers and bacteria. Finally, we discuss the current challenges and perspectives in utilizing the E-MISA strategy for disease diagnoses and therapies, particularly for clinical translation.
{"title":"Smart Molecular Imaging and Theranostic Probes by Enzymatic Molecular In Situ Self-Assembly","authors":"Xidan Wen, Chao Zhang, Yuyang Tian, Yinxing Miao, Shaohai Liu, Jing-Juan Xu, Deju Ye, Jian He","doi":"10.1021/jacsau.4c00392","DOIUrl":"https://doi.org/10.1021/jacsau.4c00392","url":null,"abstract":"Enzymatic molecular in situ self-assembly (E-MISA) that enables the synthesis of high-order nanostructures from synthetic small molecules inside a living subject has emerged as a promising strategy for molecular imaging and theranostics. This strategy leverages the catalytic activity of an enzyme to trigger probe substrate conversion and assembly in situ, permitting prolonging retention and congregating many molecules of probes in the targeted cells or tissues. Enhanced imaging signals or therapeutic functions can be achieved by responding to a specific enzyme. This E-MISA strategy has been successfully applied for the development of enzyme-activated smart molecular imaging or theranostic probes for in vivo applications. In this Perspective, we discuss the general principle of controlling in situ self-assembly of synthetic small molecules by an enzyme and then discuss the applications for the construction of “smart” imaging and theranostic probes against cancers and bacteria. Finally, we discuss the current challenges and perspectives in utilizing the E-MISA strategy for disease diagnoses and therapies, particularly for clinical translation.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lu Liu, Sicheng Fan, Wendi Wang, Sixing Yin, Zirui Lv, Jie Zhang, Jingyu Zhang, Lanhao Yang, Yuzhu Ma, Qiulong Wei, Dongyuan Zhao, Kun Lan
Mesoporous materials endowed with a hollow structure offer ample opportunities due to their integrated functionalities; however, current approaches mainly rely on the recruitment of solid rigid templates, and feasible strategies with better simplicity and tunability remain infertile. Here, we report a novel emulsion-driven coassembly method for constructing a highly tailored hollow architecture in mesoporous carbon, which can be completely processed on oil–water liquid interfaces instead of a solid rigid template. Such a facile and flexible methodology relies on the subtle employment of a 1,3,5-trimethylbenzene (TMB) additive, which acts as both an emulsion template and a swelling agent, leading to a compatible integration of oil droplets and composite micelles. The solution-based assembly process also shows high controllability, endowing the hollow carbon mesostructure with a uniform morphology of hundreds of nanometers and tunable cavities from 0 to 130 nm in diameter and porosities (mesopore sizes 2.5–7.7 nm; surface area 179–355 m2 g–1). Because of the unique features in permeability, diffusion, and surface access, the hollow mesoporous carbon nanospheres exhibit excellent high rate and cycling performances for sodium-ion storage. Our study reveals a cooperative assembly on the liquid interface, which could provide an alternative toolbox for constructing delicate mesostructures and complex hierarchies toward advanced technologies.
{"title":"Tailored Hollow Mesoporous Carbon Nanospheres from Soft Emulsions Enhance Kinetics in Sodium Batteries","authors":"Lu Liu, Sicheng Fan, Wendi Wang, Sixing Yin, Zirui Lv, Jie Zhang, Jingyu Zhang, Lanhao Yang, Yuzhu Ma, Qiulong Wei, Dongyuan Zhao, Kun Lan","doi":"10.1021/jacsau.4c00421","DOIUrl":"https://doi.org/10.1021/jacsau.4c00421","url":null,"abstract":"Mesoporous materials endowed with a hollow structure offer ample opportunities due to their integrated functionalities; however, current approaches mainly rely on the recruitment of solid rigid templates, and feasible strategies with better simplicity and tunability remain infertile. Here, we report a novel emulsion-driven coassembly method for constructing a highly tailored hollow architecture in mesoporous carbon, which can be completely processed on oil–water liquid interfaces instead of a solid rigid template. Such a facile and flexible methodology relies on the subtle employment of a 1,3,5-trimethylbenzene (TMB) additive, which acts as both an emulsion template and a swelling agent, leading to a compatible integration of oil droplets and composite micelles. The solution-based assembly process also shows high controllability, endowing the hollow carbon mesostructure with a uniform morphology of hundreds of nanometers and tunable cavities from 0 to 130 nm in diameter and porosities (mesopore sizes 2.5–7.7 nm; surface area 179–355 m<sup>2</sup> g<sup>–1</sup>). Because of the unique features in permeability, diffusion, and surface access, the hollow mesoporous carbon nanospheres exhibit excellent high rate and cycling performances for sodium-ion storage. Our study reveals a cooperative assembly on the liquid interface, which could provide an alternative toolbox for constructing delicate mesostructures and complex hierarchies toward advanced technologies.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pengcheng Huang, Yu Yan, Ricardo P. Martinho, Leon Lefferts, Bin Wang, Jimmy Faria Albanese
Enzymes can precisely control the speed and selectivity of chemical reactions by modifying locally the solvent–reactant interactions. To extrapolate these attributes to heterogeneous catalysts, we have employed thermoresponsive poly n-isopropylacrylamide (p-NIPAM) brushes bonded to silica spheres containing palladium. These polymers can form hydrogen bonds with water molecules at low temperatures (<32 °C) allowing the polymer to stay swollen. Detailed reaction kinetics of nitrite hydrogenation showed that p-NIPAM decreases the apparent activation barrier by a factor of 3 at low temperatures. Diffusion-ordered spectroscopy nuclear magnetic resonance and ab initio molecular dynamics simulations showed that when p-NIPAM is present, water molecules near the surface are less mobile. This confinement perturbs the water interaction with the metal, reducing the barrier for the proton–electron transfer reduction of nitrite. Notably, this enhancement vanishes at high temperature as the polymer collapses on itself exposing the Pd to unconfined water. The fully reversible nature of this process opens the door for creating homeostatic catalysts with controlled water-confinement.
酶可以通过局部改变溶剂与反应物之间的相互作用来精确控制化学反应的速度和选择性。为了将这些特性推广到异相催化剂中，我们采用了热膨胀性聚正异丙基丙烯酰胺（p-NIPAM）刷，将其粘合到含钯的二氧化硅球上。这些聚合物可在低温（32 °C）下与水分子形成氢键，从而使聚合物保持膨胀。亚硝酸盐氢化的详细反应动力学显示，p-NIPAM 在低温下可将表观活化障碍降低 3 倍。扩散有序光谱核磁共振和 ab initio 分子动力学模拟显示，当 p-NIPAM 存在时，表面附近的水分子流动性降低。这种限制扰乱了水与金属的相互作用，降低了亚硝酸盐的质子-电子转移还原障碍。值得注意的是，这种增强作用在高温下会消失，因为聚合物会自行塌缩，使钯暴露在未封闭的水中。这一过程的完全可逆性为创造具有可控水封闭性的同态催化剂打开了大门。
{"title":"Water Confinement on Polymer Coatings Dictates Proton–Electron Transfer on Metal-Catalyzed Hydrogenation of Nitrite","authors":"Pengcheng Huang, Yu Yan, Ricardo P. Martinho, Leon Lefferts, Bin Wang, Jimmy Faria Albanese","doi":"10.1021/jacsau.4c00389","DOIUrl":"https://doi.org/10.1021/jacsau.4c00389","url":null,"abstract":"Enzymes can precisely control the speed and selectivity of chemical reactions by modifying locally the solvent–reactant interactions. To extrapolate these attributes to heterogeneous catalysts, we have employed thermoresponsive poly <i>n</i>-isopropylacrylamide (<i>p</i>-NIPAM) brushes bonded to silica spheres containing palladium. These polymers can form hydrogen bonds with water molecules at low temperatures (<32 °C) allowing the polymer to stay swollen. Detailed reaction kinetics of nitrite hydrogenation showed that <i>p</i>-NIPAM decreases the apparent activation barrier by a factor of 3 at low temperatures. Diffusion-ordered spectroscopy nuclear magnetic resonance and ab initio molecular dynamics simulations showed that when <i>p</i>-NIPAM is present, water molecules near the surface are less mobile. This confinement perturbs the water interaction with the metal, reducing the barrier for the proton–electron transfer reduction of nitrite. Notably, this enhancement vanishes at high temperature as the polymer collapses on itself exposing the Pd to unconfined water. The fully reversible nature of this process opens the door for creating homeostatic catalysts with controlled water-confinement.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brenda Pijper, Lucía M. Saavedra, Matteo Lanzi, Maialen Alonso, Alberto Fontana, Marta Serrano, José Enrique Gómez, Arjan W. Kleij, Jesús Alcázar, Santiago Cañellas
Light-mediated reactions have emerged as an indispensable tool in organic synthesis and drug discovery, enabling novel transformations and providing access to previously unexplored chemical space. Despite their widespread application in both academic and industrial research, the utilization of light as an energy source still encounters challenges regarding reproducibility and data robustness. Herein we present a comprehensive head-to-head comparison of commercially available batch photoreactors, alongside the introduction of the use of batch and flow photoreactors in parallel synthesis. Hence, we aim to establish a reliable and consistent platform for light-mediated reactions in high-throughput mode. Herein, we showcase the identification of several platforms aligning with the rigorous demands for efficient and robust high-throughput experimentation screenings and library synthesis.
{"title":"Addressing Reproducibility Challenges in High-Throughput Photochemistry","authors":"Brenda Pijper, Lucía M. Saavedra, Matteo Lanzi, Maialen Alonso, Alberto Fontana, Marta Serrano, José Enrique Gómez, Arjan W. Kleij, Jesús Alcázar, Santiago Cañellas","doi":"10.1021/jacsau.4c00312","DOIUrl":"https://doi.org/10.1021/jacsau.4c00312","url":null,"abstract":"Light-mediated reactions have emerged as an indispensable tool in organic synthesis and drug discovery, enabling novel transformations and providing access to previously unexplored chemical space. Despite their widespread application in both academic and industrial research, the utilization of light as an energy source still encounters challenges regarding reproducibility and data robustness. Herein we present a comprehensive head-to-head comparison of commercially available batch photoreactors, alongside the introduction of the use of batch and flow photoreactors in parallel synthesis. Hence, we aim to establish a reliable and consistent platform for light-mediated reactions in high-throughput mode. Herein, we showcase the identification of several platforms aligning with the rigorous demands for efficient and robust high-throughput experimentation screenings and library synthesis.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenming Huang, Li Zhang, Tong Tang, Haijiao Wang, Yingqian Jiang, Hanwen Ren, Yitian Zhang, Jiali Fang, Wenhe Zhang, Xian Jia, Song You, Bin Qin
Biocatalysis is an effective approach for producing chiral drug intermediates that are often difficult to synthesize using traditional chemical methods. A time-efficient strategy is required to accelerate the directed evolution process to achieve the desired enzyme function. In this research, we evaluated machine learning-assisted directed evolution as a potential approach for enzyme engineering, using a moderately diastereoselective ketoreductase library as a model system. Machine learning-assisted directed evolution and traditional directed evolution methods were compared for reducing (±)-tetrabenazine to dihydrotetrabenazine via kinetic resolution facilitated by BsSDR10, a short-chain dehydrogenase/reductase from Bacillus subtilis. Both methods successfully identified variants with significantly improved diastereoselectivity for each isomer of dihydrotetrabenazine. Furthermore, the preparation of (2S,3S,11bS)-dihydrotetrabenazine has been successfully scaled up, with an isolated yield of 40.7% and a diastereoselectivity of 91.3%.
{"title":"Application of Directed Evolution and Machine Learning to Enhance the Diastereoselectivity of Ketoreductase for Dihydrotetrabenazine Synthesis","authors":"Chenming Huang, Li Zhang, Tong Tang, Haijiao Wang, Yingqian Jiang, Hanwen Ren, Yitian Zhang, Jiali Fang, Wenhe Zhang, Xian Jia, Song You, Bin Qin","doi":"10.1021/jacsau.4c00284","DOIUrl":"https://doi.org/10.1021/jacsau.4c00284","url":null,"abstract":"Biocatalysis is an effective approach for producing chiral drug intermediates that are often difficult to synthesize using traditional chemical methods. A time-efficient strategy is required to accelerate the directed evolution process to achieve the desired enzyme function. In this research, we evaluated machine learning-assisted directed evolution as a potential approach for enzyme engineering, using a moderately diastereoselective ketoreductase library as a model system. Machine learning-assisted directed evolution and traditional directed evolution methods were compared for reducing (±)-tetrabenazine to dihydrotetrabenazine via kinetic resolution facilitated by BsSDR10, a short-chain dehydrogenase/reductase from <i>Bacillus subtilis</i>. Both methods successfully identified variants with significantly improved diastereoselectivity for each isomer of dihydrotetrabenazine. Furthermore, the preparation of (2<i>S</i>,3<i>S</i>,11b<i>S</i>)-dihydrotetrabenazine has been successfully scaled up, with an isolated yield of 40.7% and a diastereoselectivity of 91.3%.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141520611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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