Pub Date : 2024-10-26DOI: 10.1038/s42004-024-01322-z
Ramon Torres-Cavanillas, Alicia Forment-Aliaga
Stimuli-responsive systems are an emerging class of materials in fields as diverse as electronics, optoelectronics, cancer detection, drug delivery, or sensing. Especially focusing on nanomaterials, 2D transition metal dichalcogenides have recently attracted the scientific community''s attention due to their remarkable intrinsic stimuli-responsive behaviour upon external stimuli such as pH, light, voltage, or certain pathogens. This significant response can be further enhanced by forming mixed-dimensional heterostructures and by molecular functionalization, capitalizing on chemistry to manipulate and boost their intrinsic stimuli-responsive properties. Furthermore, thanks to the endless possibilities of chemistry, a new class of smart materials based on the combination of stimuli-responsive molecular systems with transition metal dichalcogenides has recently been synthesized. In these materials, the physical properties of the 2D layers are reversibly modified by the switchable molecules, not only enhancing their stimuli-responsive behaviour but also providing memory to the hybrid. Therefore, this review explores the recent breakthroughs in the chemical design of smart transition metal dichalcogenides with built-in responsiveness. Transition metal dichalcogenides not only possess intrinsic stimuli-responsive behaviours upon exposure to external stimuli, but molecular functionalization of these materials and/or combination with other materials to form mixed-dimensional heterostructures enables the manipulation and enhancement of their stimuli-responsive properties. Here, the authors review recent breakthroughs in the chemical design of smart transition metal dichalcogenides with built-in responsiveness.
{"title":"Design of stimuli-responsive transition metal dichalcogenides","authors":"Ramon Torres-Cavanillas, Alicia Forment-Aliaga","doi":"10.1038/s42004-024-01322-z","DOIUrl":"10.1038/s42004-024-01322-z","url":null,"abstract":"Stimuli-responsive systems are an emerging class of materials in fields as diverse as electronics, optoelectronics, cancer detection, drug delivery, or sensing. Especially focusing on nanomaterials, 2D transition metal dichalcogenides have recently attracted the scientific community''s attention due to their remarkable intrinsic stimuli-responsive behaviour upon external stimuli such as pH, light, voltage, or certain pathogens. This significant response can be further enhanced by forming mixed-dimensional heterostructures and by molecular functionalization, capitalizing on chemistry to manipulate and boost their intrinsic stimuli-responsive properties. Furthermore, thanks to the endless possibilities of chemistry, a new class of smart materials based on the combination of stimuli-responsive molecular systems with transition metal dichalcogenides has recently been synthesized. In these materials, the physical properties of the 2D layers are reversibly modified by the switchable molecules, not only enhancing their stimuli-responsive behaviour but also providing memory to the hybrid. Therefore, this review explores the recent breakthroughs in the chemical design of smart transition metal dichalcogenides with built-in responsiveness. Transition metal dichalcogenides not only possess intrinsic stimuli-responsive behaviours upon exposure to external stimuli, but molecular functionalization of these materials and/or combination with other materials to form mixed-dimensional heterostructures enables the manipulation and enhancement of their stimuli-responsive properties. Here, the authors review recent breakthroughs in the chemical design of smart transition metal dichalcogenides with built-in responsiveness.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-14"},"PeriodicalIF":5.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01322-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1038/s42004-024-01316-x
Obaid Mohiuddin, Henri de Maissin, Andrey N. Pravdivtsev, Arne Brahms, Marvin Herzog, Leif Schröder, Eduard Y. Chekmenev, Rainer Herges, Jan-Bernd Hövener, Maxim Zaitsev, Dominik von Elverfeldt, Andreas B. Schmidt
Hyperpolarized 13C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high 13C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-13C]acetate and [1-13C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized to P13C ≈ 28% at 80 mM concentration and P13C ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone-d6 at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar). We optimized the hyperpolarization process, reducing it to under 10 s, and employed advanced pulse sequences to enhance the polarization transfer efficiency. The hyperpolarization system has a small footprint, allowing it to be positioned in the same magnet, where 13C MRI is performed. We exemplified the utility of the design with sub-second in situ 13C MRI of ethyl [1-13C]pyruvate-d6. However, challenges remain in side-arm cleavage and purification in the MRI system to extract highly polarized aqueous agent solutions. Our results showcase efficient and rapid 13C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized 13C MRI. Hyperpolarized 13C MRI visualizes real-time metabolic processes in vivo, however, external polarizers are commonly required to produce hyperpolarized metabolites. Here, using a parahydrogen-based approach, the authors achieved up to 30% 13C polarization in situ in an MRI system for precursor molecules [1-13C]acetate and [1-13C]pyruvate ethyl esters in their perdeuterated forms, potentially facilitating future metabolic imaging applications.
{"title":"Rapid in situ carbon-13 hyperpolarization and imaging of acetate and pyruvate esters without external polarizer","authors":"Obaid Mohiuddin, Henri de Maissin, Andrey N. Pravdivtsev, Arne Brahms, Marvin Herzog, Leif Schröder, Eduard Y. Chekmenev, Rainer Herges, Jan-Bernd Hövener, Maxim Zaitsev, Dominik von Elverfeldt, Andreas B. Schmidt","doi":"10.1038/s42004-024-01316-x","DOIUrl":"10.1038/s42004-024-01316-x","url":null,"abstract":"Hyperpolarized 13C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high 13C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-13C]acetate and [1-13C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized to P13C ≈ 28% at 80 mM concentration and P13C ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone-d6 at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar). We optimized the hyperpolarization process, reducing it to under 10 s, and employed advanced pulse sequences to enhance the polarization transfer efficiency. The hyperpolarization system has a small footprint, allowing it to be positioned in the same magnet, where 13C MRI is performed. We exemplified the utility of the design with sub-second in situ 13C MRI of ethyl [1-13C]pyruvate-d6. However, challenges remain in side-arm cleavage and purification in the MRI system to extract highly polarized aqueous agent solutions. Our results showcase efficient and rapid 13C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized 13C MRI. Hyperpolarized 13C MRI visualizes real-time metabolic processes in vivo, however, external polarizers are commonly required to produce hyperpolarized metabolites. Here, using a parahydrogen-based approach, the authors achieved up to 30% 13C polarization in situ in an MRI system for precursor molecules [1-13C]acetate and [1-13C]pyruvate ethyl esters in their perdeuterated forms, potentially facilitating future metabolic imaging applications.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":5.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1038/s42004-024-01293-1
Dominik Spahr, Lkhamsuren Bayarjargal, Maxim Bykov, Lukas Brüning, Pascal L. Jurzick, Yu Wang, Victor Milman, Keith Refson, Mohamed Mezouar, Björn Winkler
Understanding the fate of subducted carbonates is a prerequisite for the elucidation of the Earth’s deep carbon cycle. Here we show that the concomitant presence of Ca[CO3] with CO2 in a subducting slab very likely results in the formation of an anhydrous mixed pyrocarbonate, $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ , at moderate pressure ( ≈ 20 GPa) and temperature ( ≈ 1500 K) conditions. We show that at these conditions $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ can be obtained by reacting Ca[CO3] with CO2 in a laser-heated diamond anvil cell. The crystal structure was obtained from synchrotron-based single crystal X-ray diffraction data. Density Functional Perturbation Theory calculations in combination with experimental Raman spectroscopy results unambiguously confirmed the structural model. The crystal structure of $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ is characterized by the presence of $${left[{{{{rm{CO}}}}}_{3}right]}^{2-}$$ - and $${left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}^{2-}$$ -groups. The results presented here imply that the formation of $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ needs to be taken into account when constructing models of the deep carbon cycle of the Earth. Carbonates are transported into the deep Earth by subduction of the oceanic lithosphere, but the stability fields of subducted carbonates as a function of pressure, temperature, and composition remain incompletely described. Here, the authors synthesize the anhydrous, mixed pyrocarbonate Ca3[C2O5]2[CO3] from Ca[CO3] and CO2 in a laser-heated diamond anvil cell at moderate pressure and elucidate its structural features.
了解俯冲碳酸盐的命运是阐明地球深部碳循环的先决条件。在这里，我们展示了在中等压力（≈ 20 GPa）和温度（≈ 1500 K）条件下，Ca[CO3]与二氧化碳同时存在于俯冲板块中很可能会形成无水混合碳酸氢盐--Ca 3 C 2 O 5 2 CO 3。我们的研究表明，在这些条件下，通过在激光加热的金刚石砧槽中使 Ca[CO3] 与 CO2 反应，可以得到 Ca 3 C 2 O 5 2 CO 3。晶体结构是从同步辐射单晶 X 射线衍射数据中获得的。密度泛函扰动理论计算结合拉曼光谱实验结果明确证实了该结构模型。Ca 3 C 2 O 5 2 CO 3 晶体结构的特点是存在 CO 3 2 - 和 C 2 O 5 2 - 基团。本文介绍的结果表明，在构建地球深层碳循环模型时，需要考虑 Ca 3 C 2 O 5 2 CO 3 的形成。
{"title":"Ca3[C2O5]2[CO3] is a pyrocarbonate which can be formed at p, T-conditions prevalent in the Earth’s transition zone","authors":"Dominik Spahr, Lkhamsuren Bayarjargal, Maxim Bykov, Lukas Brüning, Pascal L. Jurzick, Yu Wang, Victor Milman, Keith Refson, Mohamed Mezouar, Björn Winkler","doi":"10.1038/s42004-024-01293-1","DOIUrl":"10.1038/s42004-024-01293-1","url":null,"abstract":"Understanding the fate of subducted carbonates is a prerequisite for the elucidation of the Earth’s deep carbon cycle. Here we show that the concomitant presence of Ca[CO3] with CO2 in a subducting slab very likely results in the formation of an anhydrous mixed pyrocarbonate, $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ , at moderate pressure ( ≈ 20 GPa) and temperature ( ≈ 1500 K) conditions. We show that at these conditions $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ can be obtained by reacting Ca[CO3] with CO2 in a laser-heated diamond anvil cell. The crystal structure was obtained from synchrotron-based single crystal X-ray diffraction data. Density Functional Perturbation Theory calculations in combination with experimental Raman spectroscopy results unambiguously confirmed the structural model. The crystal structure of $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ is characterized by the presence of $${left[{{{{rm{CO}}}}}_{3}right]}^{2-}$$ - and $${left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}^{2-}$$ -groups. The results presented here imply that the formation of $${{{{rm{Ca}}}}}_{3}{left[{{{{rm{C}}}}}_{2}{{{{rm{O}}}}}_{5}right]}_{2}left[{{{{rm{CO}}}}}_{3}right]$$ needs to be taken into account when constructing models of the deep carbon cycle of the Earth. Carbonates are transported into the deep Earth by subduction of the oceanic lithosphere, but the stability fields of subducted carbonates as a function of pressure, temperature, and composition remain incompletely described. Here, the authors synthesize the anhydrous, mixed pyrocarbonate Ca3[C2O5]2[CO3] from Ca[CO3] and CO2 in a laser-heated diamond anvil cell at moderate pressure and elucidate its structural features.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-7"},"PeriodicalIF":5.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1038/s42004-024-01250-y
Yann Sakref, Olivier Rivoire
The difficulty of designing simple autocatalysts that grow exponentially in the absence of enzymes, external drives or ingenious internal mechanisms severely constrains scenarios for the emergence of evolution by natural selection in chemical and physical systems. Here, we systematically analyze these difficulties in the simplest and most generic autocatalyst: a dimeric molecule that duplicates by templated ligation. We show that despite its simplicity, such an autocatalyst can achieve exponential growth autonomously. We also show, however, that it is possible to design as simple sub-exponential autocatalysts that have an advantage over exponential autocatalysts when competing for a common resource. We reach these conclusions by developing a theoretical framework based on kinetic barrier diagrams. Besides challenging commonly accepted assumptions in the field of the origin of life, our results provide a blueprint for the experimental realization of elementary autocatalysts exhibiting a form of natural selection, whether on a molecular or colloidal scale. Autocatalysis plays an important role in the origin of life and molecular evolution, however, designing simple autocatalysts that grow exponentially remains challenging. Here, the authors computationally design simple autocatalysts-- dimeric molecules that duplicate by templated ligation, --and show that these autocatalysts can achieve exponential growth autonomously.
{"title":"Design principles, growth laws, and competition of minimal autocatalysts","authors":"Yann Sakref, Olivier Rivoire","doi":"10.1038/s42004-024-01250-y","DOIUrl":"10.1038/s42004-024-01250-y","url":null,"abstract":"The difficulty of designing simple autocatalysts that grow exponentially in the absence of enzymes, external drives or ingenious internal mechanisms severely constrains scenarios for the emergence of evolution by natural selection in chemical and physical systems. Here, we systematically analyze these difficulties in the simplest and most generic autocatalyst: a dimeric molecule that duplicates by templated ligation. We show that despite its simplicity, such an autocatalyst can achieve exponential growth autonomously. We also show, however, that it is possible to design as simple sub-exponential autocatalysts that have an advantage over exponential autocatalysts when competing for a common resource. We reach these conclusions by developing a theoretical framework based on kinetic barrier diagrams. Besides challenging commonly accepted assumptions in the field of the origin of life, our results provide a blueprint for the experimental realization of elementary autocatalysts exhibiting a form of natural selection, whether on a molecular or colloidal scale. Autocatalysis plays an important role in the origin of life and molecular evolution, however, designing simple autocatalysts that grow exponentially remains challenging. Here, the authors computationally design simple autocatalysts-- dimeric molecules that duplicate by templated ligation, --and show that these autocatalysts can achieve exponential growth autonomously.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-19DOI: 10.1038/s42004-024-01327-8
Brian S. Mantilla, Jack S. White, William R. T. Mosedale, Andrew Gomm, Adam Nelson, Terry K. Smith, Megan H. Wright
Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei. Four of the probes were found to have sub-micromolar anti-trypanosomal activity. A chemical proteomic approach, harnessing an alkynylated analogue and broad-spectrum fluorophosphonate tools, provided insights into the observed anti-trypanosomal activity, which likely stems from covalent modification of multiple protein targets. It is envisaged that the unified diversity-oriented approach may enable the discovery of electrophilic probes that have value in the elucidation of biological and biomedical mechanisms. Electrophilic bioactive compounds are useful chemical tools for identifying and modulating protein targets through reaction with nucleophilic amino acid side chain residues. Here, the authors report a modular synthesis of electrophilic sulfonyl fluoride probes, and evaluate their anti-trypanosomal activity using a chemoproteomics approach
{"title":"Discovery of Trypanosoma brucei inhibitors enabled by a unified synthesis of diverse sulfonyl fluorides","authors":"Brian S. Mantilla, Jack S. White, William R. T. Mosedale, Andrew Gomm, Adam Nelson, Terry K. Smith, Megan H. Wright","doi":"10.1038/s42004-024-01327-8","DOIUrl":"10.1038/s42004-024-01327-8","url":null,"abstract":"Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei. Four of the probes were found to have sub-micromolar anti-trypanosomal activity. A chemical proteomic approach, harnessing an alkynylated analogue and broad-spectrum fluorophosphonate tools, provided insights into the observed anti-trypanosomal activity, which likely stems from covalent modification of multiple protein targets. It is envisaged that the unified diversity-oriented approach may enable the discovery of electrophilic probes that have value in the elucidation of biological and biomedical mechanisms. Electrophilic bioactive compounds are useful chemical tools for identifying and modulating protein targets through reaction with nucleophilic amino acid side chain residues. Here, the authors report a modular synthesis of electrophilic sulfonyl fluoride probes, and evaluate their anti-trypanosomal activity using a chemoproteomics approach","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":5.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01327-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1038/s42004-024-01324-x
Shuang Hao, Brian Guthrie, Soo-Kyung Kim, Sergej Balanda, Jan Kubicek, Babar Murtaza, Naim A. Khan, Pouyan Khakbaz, Judith Su, William A. Goddard III
Sucrose provides both sweetness and energy by binding to both Venus flytrap domains (VFD) of the heterodimeric sweet taste receptor (T1R2/T1R3). In contrast, non-caloric sweeteners such as sucralose and aspartame only bind to one specific domain (VFD2) of T1R2, resulting in high-intensity sweetness. In this study, we investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites: VFD2, VFD3, transmembrane domain 2 (TMD2), and TMD3 through binding experiments and computational docking studies. Our docking results reveal multiple binding sites for the tested ligands, including the radiolabeled ligands. Our experimental evidence demonstrates that the C20 carboxy terminus of the Gα protein can bind to the intracellular region of either TMD2 or TMD3, altering GPCR affinity to the high-affinity state for steviol glycosides. These findings provide a mechanistic understanding of the structure and function of this heterodimeric sweet taste receptor. Sucrose and other non-caloric sweeteners can bind to different domains of the heterodimeric sweet taste receptor (T1R2/T1R3), resulting in different levels of sweetness. Here, the authors investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites of T1R2/T1R3 through binding experiments and computational docking studies, revealing multiple binding sites for the tested ligands and structural– function correlations of ligand–receptor interactions.
{"title":"Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments","authors":"Shuang Hao, Brian Guthrie, Soo-Kyung Kim, Sergej Balanda, Jan Kubicek, Babar Murtaza, Naim A. Khan, Pouyan Khakbaz, Judith Su, William A. Goddard III","doi":"10.1038/s42004-024-01324-x","DOIUrl":"10.1038/s42004-024-01324-x","url":null,"abstract":"Sucrose provides both sweetness and energy by binding to both Venus flytrap domains (VFD) of the heterodimeric sweet taste receptor (T1R2/T1R3). In contrast, non-caloric sweeteners such as sucralose and aspartame only bind to one specific domain (VFD2) of T1R2, resulting in high-intensity sweetness. In this study, we investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites: VFD2, VFD3, transmembrane domain 2 (TMD2), and TMD3 through binding experiments and computational docking studies. Our docking results reveal multiple binding sites for the tested ligands, including the radiolabeled ligands. Our experimental evidence demonstrates that the C20 carboxy terminus of the Gα protein can bind to the intracellular region of either TMD2 or TMD3, altering GPCR affinity to the high-affinity state for steviol glycosides. These findings provide a mechanistic understanding of the structure and function of this heterodimeric sweet taste receptor. Sucrose and other non-caloric sweeteners can bind to different domains of the heterodimeric sweet taste receptor (T1R2/T1R3), resulting in different levels of sweetness. Here, the authors investigate the binding mechanism of various steviol glycosides, artificial sweeteners, and a negative allosteric modulator (lactisole) at four distinct binding sites of T1R2/T1R3 through binding experiments and computational docking studies, revealing multiple binding sites for the tested ligands and structural– function correlations of ligand–receptor interactions.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-17"},"PeriodicalIF":5.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01324-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1038/s42004-024-01313-0
Ivan A. Trofimov, Oleg G. Salnikov, Andrey N. Pravdivtsev, Henri de Maissin, Anna P. Yi, Eduard Y. Chekmenev, Jan-Bernd Hövener, Andreas B. Schmidt, Igor V. Koptyug
Radio Amplification by Stimulated Emission of Radiation (RASER) is a phenomenon observed during nuclear magnetic resonance (NMR) experiments with strongly negatively polarized systems. This phenomenon may be utilized for the production of very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Recently, novel methods of producing RASER by ParaHydrogen-Induced Polarization (PHIP) were introduced. Here, we show that pairwise addition of parahydrogen to various propargylic compounds induces RASER activity of other protons beyond those chemically introduced in the reaction. In high-field PHIP, negative polarization initiating RASER is transferred via intramolecular cross-relaxation. When parahydrogen is added in Earth’s field followed by adiabatic transfer to a high field, RASER activity of other protons is induced via both J-couplings and cross-relaxation. This through-bond and through-space induction of RASER holds potential for the ongoing development and expansion of RASER applications and can potentially enhance spectral resolution in two-dimensional NMR spectroscopy techniques. Radio Amplification by Stimulated Emission of Radiation (RASER) may produce very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Here, the authors show that pairwise addition of parahydrogen to various propargylic compounds induces RASER activity of other protons beyond those chemically introduced in the reaction via through-bond or through-space interactions.
{"title":"Through-bond and through-space radiofrequency amplification by stimulated emission of radiation","authors":"Ivan A. Trofimov, Oleg G. Salnikov, Andrey N. Pravdivtsev, Henri de Maissin, Anna P. Yi, Eduard Y. Chekmenev, Jan-Bernd Hövener, Andreas B. Schmidt, Igor V. Koptyug","doi":"10.1038/s42004-024-01313-0","DOIUrl":"10.1038/s42004-024-01313-0","url":null,"abstract":"Radio Amplification by Stimulated Emission of Radiation (RASER) is a phenomenon observed during nuclear magnetic resonance (NMR) experiments with strongly negatively polarized systems. This phenomenon may be utilized for the production of very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Recently, novel methods of producing RASER by ParaHydrogen-Induced Polarization (PHIP) were introduced. Here, we show that pairwise addition of parahydrogen to various propargylic compounds induces RASER activity of other protons beyond those chemically introduced in the reaction. In high-field PHIP, negative polarization initiating RASER is transferred via intramolecular cross-relaxation. When parahydrogen is added in Earth’s field followed by adiabatic transfer to a high field, RASER activity of other protons is induced via both J-couplings and cross-relaxation. This through-bond and through-space induction of RASER holds potential for the ongoing development and expansion of RASER applications and can potentially enhance spectral resolution in two-dimensional NMR spectroscopy techniques. Radio Amplification by Stimulated Emission of Radiation (RASER) may produce very narrow NMR lines, background-free NMR spectroscopy, and excitation-free sensing of chemical transformations. Here, the authors show that pairwise addition of parahydrogen to various propargylic compounds induces RASER activity of other protons beyond those chemically introduced in the reaction via through-bond or through-space interactions.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":5.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01313-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1038/s42004-024-01314-z
Malika Jeffries-EL is the Senior Dean of the Graduate School in Arts and Sciences and Professor of Chemistry and Materials Science at Boston University. Professor Jeffries-EL’s research focuses on the development of organic semiconductors—materials that combine the processing properties of polymers with the electronic properties of semiconductors.
{"title":"Women in Chemistry: Q&A with Professor Malika Jeffries-EL","authors":"","doi":"10.1038/s42004-024-01314-z","DOIUrl":"10.1038/s42004-024-01314-z","url":null,"abstract":"Malika Jeffries-EL is the Senior Dean of the Graduate School in Arts and Sciences and Professor of Chemistry and Materials Science at Boston University. Professor Jeffries-EL’s research focuses on the development of organic semiconductors—materials that combine the processing properties of polymers with the electronic properties of semiconductors.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-2"},"PeriodicalIF":5.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01314-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1038/s42004-024-01318-9
Geoffrey W. Abbott, Rían W. Manville
Plants remain an important source of biologically active small molecules with high therapeutic potential. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 (KCNQ2/3) heteromers is a major target for anticonvulsant drug development. Here, we screened 1444 extracts primarily from plants collected in California and the US Virgin Islands, for their ability to activate Kv7.2/3 but not inhibit Kv1.3, to select against tannic acid being the active component. We validated the 7 strongest hits, identified Thespesia populnea (miro, milo, portia tree) as the most promising, then discovered its primary active metabolite to be gentisic acid (GA). GA highly potently activated Kv7.2/3 (EC50, 2.8 nM). GA is, uniquely to our knowledge, 100% selective for Kv7.3 versus other Kv7 homomers; it requires S5 residue Kv7.3-W265 for Kv7.2/3 activation, and it ameliorates pentylenetetrazole-induced seizures in mice. Structure-activity studies revealed that the FDA-approved vasoprotective drug calcium dobesilate, a GA analog, is a previously unrecognized Kv7.2/3 channel opener. Also an active aspirin metabolite, GA provides a molecular rationale for the use of T. populnea as an anticonvulsant in Polynesian indigenous medicine and presents novel pharmacological prospects for potent, isoform-selective, therapeutic Kv7 channel activation. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 heteromers is a major target for anticonvulsant drug development, however, specificity and potency are key challenges for Kv7.2/3 opener development. Here, the authors report the discovery of gentisic acid as a potent and selective Kv7.3 opener from Thespesia populnea — a plant reportedly used as an anticonvulsant in Polynesian traditional medicine.
{"title":"Discovery of a potent, Kv7.3-selective potassium channel opener from a Polynesian traditional botanical anticonvulsant","authors":"Geoffrey W. Abbott, Rían W. Manville","doi":"10.1038/s42004-024-01318-9","DOIUrl":"10.1038/s42004-024-01318-9","url":null,"abstract":"Plants remain an important source of biologically active small molecules with high therapeutic potential. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 (KCNQ2/3) heteromers is a major target for anticonvulsant drug development. Here, we screened 1444 extracts primarily from plants collected in California and the US Virgin Islands, for their ability to activate Kv7.2/3 but not inhibit Kv1.3, to select against tannic acid being the active component. We validated the 7 strongest hits, identified Thespesia populnea (miro, milo, portia tree) as the most promising, then discovered its primary active metabolite to be gentisic acid (GA). GA highly potently activated Kv7.2/3 (EC50, 2.8 nM). GA is, uniquely to our knowledge, 100% selective for Kv7.3 versus other Kv7 homomers; it requires S5 residue Kv7.3-W265 for Kv7.2/3 activation, and it ameliorates pentylenetetrazole-induced seizures in mice. Structure-activity studies revealed that the FDA-approved vasoprotective drug calcium dobesilate, a GA analog, is a previously unrecognized Kv7.2/3 channel opener. Also an active aspirin metabolite, GA provides a molecular rationale for the use of T. populnea as an anticonvulsant in Polynesian indigenous medicine and presents novel pharmacological prospects for potent, isoform-selective, therapeutic Kv7 channel activation. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 heteromers is a major target for anticonvulsant drug development, however, specificity and potency are key challenges for Kv7.2/3 opener development. Here, the authors report the discovery of gentisic acid as a potent and selective Kv7.3 opener from Thespesia populnea — a plant reportedly used as an anticonvulsant in Polynesian traditional medicine.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":5.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01318-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1038/s42004-024-01319-8
Jinping Hu, Paul D. Asimow, Chi Ma, Paul J. Steinhardt, Luca Bindi
Quasicrystals are of interest because of their unique nonperiodic structures and physical properties. Motivated by naturally occurring icosahedral AlCuFe- and decagonal AlNiFe-phases hosted in a shocked meteorite, different laboratories have undertaken a series of shock recovery experiments to understand their formation mechanism. Shock experiments generate a complex series of processes and conditions, including a near-instantaneous excursion to high pressure and high temperature, large shear stresses, local melting, rapid decompression, fast quenching and post-shock annealing. This highly dynamic scenario offers a very useful but imperfect tool for exploring the stability of novel alloys, such as quasicrystals. So far, all the shock-synthesized quasicrystals differ considerably in composition from any thermodynamically stable or metastable quasicrystals synthesized by metallurgical techniques at low pressure, leaving plenty of questions to be answered about their formation conditions and their nucleation and growth mechanisms occurring during shock experiments. In this Perspective, we summarize the previous studies of shock-synthesized quasicrystals and discuss the advantages and difficulties caused by the experimental complexity. We also propose a few directions for future experiments to better control the shock conditions and understand the properties of quasicrystals. Shock compression is a highly dynamic, useful tool for exploring the stability of novel alloys such as quasicrystals, but their formation conditions and the nucleation-growth mechanisms occurring during shock experiments remain largely elusive. Here, the authors provide a summary of quasicrystal shock-syntheses and discuss the advantages and difficulties caused by the experimental complexity.
{"title":"Quasicrystal synthesis by shock compression","authors":"Jinping Hu, Paul D. Asimow, Chi Ma, Paul J. Steinhardt, Luca Bindi","doi":"10.1038/s42004-024-01319-8","DOIUrl":"10.1038/s42004-024-01319-8","url":null,"abstract":"Quasicrystals are of interest because of their unique nonperiodic structures and physical properties. Motivated by naturally occurring icosahedral AlCuFe- and decagonal AlNiFe-phases hosted in a shocked meteorite, different laboratories have undertaken a series of shock recovery experiments to understand their formation mechanism. Shock experiments generate a complex series of processes and conditions, including a near-instantaneous excursion to high pressure and high temperature, large shear stresses, local melting, rapid decompression, fast quenching and post-shock annealing. This highly dynamic scenario offers a very useful but imperfect tool for exploring the stability of novel alloys, such as quasicrystals. So far, all the shock-synthesized quasicrystals differ considerably in composition from any thermodynamically stable or metastable quasicrystals synthesized by metallurgical techniques at low pressure, leaving plenty of questions to be answered about their formation conditions and their nucleation and growth mechanisms occurring during shock experiments. In this Perspective, we summarize the previous studies of shock-synthesized quasicrystals and discuss the advantages and difficulties caused by the experimental complexity. We also propose a few directions for future experiments to better control the shock conditions and understand the properties of quasicrystals. Shock compression is a highly dynamic, useful tool for exploring the stability of novel alloys such as quasicrystals, but their formation conditions and the nucleation-growth mechanisms occurring during shock experiments remain largely elusive. Here, the authors provide a summary of quasicrystal shock-syntheses and discuss the advantages and difficulties caused by the experimental complexity.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":5.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01319-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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