Pub Date : 2024-11-19DOI: 10.1038/s42004-024-01352-7
Satyaveni Malasala, Fereshteh Azimian, Yan-Hua Chen, Jeffery L Twiss, Christi Boykin, Shayan Nik Akhtar, Qun Lu
Maintaining body homeostasis is the ultimate key to health. There are rich resources of bioactive materials for the functionality of homeostatic modulators (HMs) from both natural and synthetic chemical repertories1-3. HMs are powerful modern therapeutics for human diseases including neuropsychiatric diseases, mental disorders, and drug addiction (e.g. Buspirone and benzodiazepines)4-7. However, the identification of therapeutic HMs are often unpredictable and limited to membrane protein receptors and ion channels. Based on a serendipitously encountered small molecule ZCL278 with partial agonist (PA) profile as a model compound8-10, the Mant-GTP fluorophore-based Cdc42-GEF (guanine nucleotide exchange factor) screening uncovered a near holistic spectrum of HMs for Cdc42, a cytoplasmic small GTPase in the Ras superfamily11,12. We categorized these HMs as functionally distinct, with some previously understudied classes: Class I-competitive PAs, Class II-hormetic agonists, Class III-bona fide inhibitors, Class IV-bona fide activators, and Class V-ligand-enhanced agonists. The model HMs elicited striking biological functionalities in modulating bradykinin activation of Cdc42 signaling as well as actin remodeling while they ameliorated Alzheimer's disease-like social behavior in mouse model. Furthermore, molecular structural modeling analyses led to the concept of preferential binding pocket order (PBPO) for profiling HMs that target Cdc42 complexed with intersectin (ITSN), a GEF selectively activating Cdc42. Remarkably, the PBPO enabled a prediction of HM class that mimics the pharmacological functionality. Therefore, our study highlights a model path to actively capture different classes of HM to broaden therapeutic landscape.
{"title":"Enabling systemic identification and functionality profiling for Cdc42 homeostatic modulators.","authors":"Satyaveni Malasala, Fereshteh Azimian, Yan-Hua Chen, Jeffery L Twiss, Christi Boykin, Shayan Nik Akhtar, Qun Lu","doi":"10.1038/s42004-024-01352-7","DOIUrl":"https://doi.org/10.1038/s42004-024-01352-7","url":null,"abstract":"<p><p>Maintaining body homeostasis is the ultimate key to health. There are rich resources of bioactive materials for the functionality of homeostatic modulators (HMs) from both natural and synthetic chemical repertories<sup>1-3</sup>. HMs are powerful modern therapeutics for human diseases including neuropsychiatric diseases, mental disorders, and drug addiction (e.g. Buspirone and benzodiazepines)<sup>4-7</sup>. However, the identification of therapeutic HMs are often unpredictable and limited to membrane protein receptors and ion channels. Based on a serendipitously encountered small molecule ZCL278 with partial agonist (PA) profile as a model compound<sup>8-10</sup>, the Mant-GTP fluorophore-based Cdc42-GEF (guanine nucleotide exchange factor) screening uncovered a near holistic spectrum of HMs for Cdc42, a cytoplasmic small GTPase in the Ras superfamily<sup>11,12</sup>. We categorized these HMs as functionally distinct, with some previously understudied classes: Class I-competitive PAs, Class II-hormetic agonists, Class III-bona fide inhibitors, Class IV-bona fide activators, and Class V-ligand-enhanced agonists. The model HMs elicited striking biological functionalities in modulating bradykinin activation of Cdc42 signaling as well as actin remodeling while they ameliorated Alzheimer's disease-like social behavior in mouse model. Furthermore, molecular structural modeling analyses led to the concept of preferential binding pocket order (PBPO) for profiling HMs that target Cdc42 complexed with intersectin (ITSN), a GEF selectively activating Cdc42. Remarkably, the PBPO enabled a prediction of HM class that mimics the pharmacological functionality. Therefore, our study highlights a model path to actively capture different classes of HM to broaden therapeutic landscape.</p>","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"7 1","pages":"271"},"PeriodicalIF":5.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Using GPU-accelerated state-vector emulation, we propose to embed a quantum computing ansatz into density-functional theory via density-based basis-set corrections to obtain quantitative quantum-chemistry results on molecules that would otherwise require brute-force quantum calculations using hundreds of logical qubits. Indeed, accessing a quantitative description of chemical systems while minimizing quantum resources is an essential challenge given the limited qubit capabilities of current quantum processors. We provide a shortcut towards chemically accurate quantum computations by approaching the complete-basis-set limit through coupling the density-based basis-set corrections approach, applied to any given variational ansatz, to an on-the-fly crafting of basis sets specifically adapted to a given system and user-defined qubit budget. The resulting approach self-consistently accelerates the basis-set convergence, improving electronic densities, ground-state energies, and first-order properties (e.g. dipole moments), but can also serve as a classical, a posteriori, energy correction to quantum hardware calculations with expected applications in drug design and materials science. Quantum computing offers a promising approach to solving electronic-structure problems, but a quantitative description of chemical systems while minimizing computing resources is an essential challenge. Here, the authors provide a shortcut towards chemically accurate quantum computations by approaching the complete-basis-set limit through coupling the density-based basis-set corrections approach, applied to any given variational ansatz, to an on-the-fly crafting of basis sets specifically adapted to a given system and user-defined qubit budget.
{"title":"Shortcut to chemically accurate quantum computing via density-based basis-set correction","authors":"Diata Traore, Olivier Adjoua, César Feniou, Ioanna-Maria Lygatsika, Yvon Maday, Evgeny Posenitskiy, Kerstin Hammernik, Alberto Peruzzo, Julien Toulouse, Emmanuel Giner, Jean-Philip Piquemal","doi":"10.1038/s42004-024-01348-3","DOIUrl":"10.1038/s42004-024-01348-3","url":null,"abstract":"Using GPU-accelerated state-vector emulation, we propose to embed a quantum computing ansatz into density-functional theory via density-based basis-set corrections to obtain quantitative quantum-chemistry results on molecules that would otherwise require brute-force quantum calculations using hundreds of logical qubits. Indeed, accessing a quantitative description of chemical systems while minimizing quantum resources is an essential challenge given the limited qubit capabilities of current quantum processors. We provide a shortcut towards chemically accurate quantum computations by approaching the complete-basis-set limit through coupling the density-based basis-set corrections approach, applied to any given variational ansatz, to an on-the-fly crafting of basis sets specifically adapted to a given system and user-defined qubit budget. The resulting approach self-consistently accelerates the basis-set convergence, improving electronic densities, ground-state energies, and first-order properties (e.g. dipole moments), but can also serve as a classical, a posteriori, energy correction to quantum hardware calculations with expected applications in drug design and materials science. Quantum computing offers a promising approach to solving electronic-structure problems, but a quantitative description of chemical systems while minimizing computing resources is an essential challenge. Here, the authors provide a shortcut towards chemically accurate quantum computations by approaching the complete-basis-set limit through coupling the density-based basis-set corrections approach, applied to any given variational ansatz, to an on-the-fly crafting of basis sets specifically adapted to a given system and user-defined qubit budget.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-13"},"PeriodicalIF":5.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01348-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665218","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 : 2024-11-17DOI: 10.1038/s42004-024-01347-4
Yuming Su, Guangming Wang, Boyi Fu, Xixi Piao, Kaka Zhang
Organic phosphorescent materials have great prospects for application, whose performance particularly depends on the preparation method. Inspired by nature’s wisdom, we report a phosphor that can utilize monomers in its environment by polymerization to construct a rigid microenvironment under light illumination, leading to a glow-in-the-dark emulsion with a phosphorescence lifetime of 1 s in water. This phosphor can achieve active growth of the aqueous emulsion with the introduction of more monomers. In the presence of trace amounts of oxygen (which has adverse effects on both polymerization and afterglow), this phosphor can still undergo photo-induced polymerization, removing the influence of oxygen and obtaining afterglow emulsion, demonstrating its adaptability to the environment. This phosphor can also catalyze the polymerization of monomers containing yellow fluorophore, obtaining long-lifetime yellow afterglow emulsion through excited state energy transfer. We have also conducted in-depth studies on the photo-catalytic and phosphorescent properties of this phosphor in model systems. This biomimetic intelligent manufacturing provides a new approach for organic phosphorescent materials and is significant for future applications. Organic afterglow materials show great potential in diverse applications, and their performance particularly depends on their method of preparation. Here, the authors report a biomimetic phosphor that builds a rigid microenvironment to restrain non-radiative decay of triplet excitons, achieving long-lived organic afterglow in water.
{"title":"A biomimetic phosphor that can build a rigid microenvironment for its long-lived afterglow in aqueous medium","authors":"Yuming Su, Guangming Wang, Boyi Fu, Xixi Piao, Kaka Zhang","doi":"10.1038/s42004-024-01347-4","DOIUrl":"10.1038/s42004-024-01347-4","url":null,"abstract":"Organic phosphorescent materials have great prospects for application, whose performance particularly depends on the preparation method. Inspired by nature’s wisdom, we report a phosphor that can utilize monomers in its environment by polymerization to construct a rigid microenvironment under light illumination, leading to a glow-in-the-dark emulsion with a phosphorescence lifetime of 1 s in water. This phosphor can achieve active growth of the aqueous emulsion with the introduction of more monomers. In the presence of trace amounts of oxygen (which has adverse effects on both polymerization and afterglow), this phosphor can still undergo photo-induced polymerization, removing the influence of oxygen and obtaining afterglow emulsion, demonstrating its adaptability to the environment. This phosphor can also catalyze the polymerization of monomers containing yellow fluorophore, obtaining long-lifetime yellow afterglow emulsion through excited state energy transfer. We have also conducted in-depth studies on the photo-catalytic and phosphorescent properties of this phosphor in model systems. This biomimetic intelligent manufacturing provides a new approach for organic phosphorescent materials and is significant for future applications. Organic afterglow materials show great potential in diverse applications, and their performance particularly depends on their method of preparation. Here, the authors report a biomimetic phosphor that builds a rigid microenvironment to restrain non-radiative decay of triplet excitons, achieving long-lived organic afterglow in water.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01347-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643904","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 : 2024-11-16DOI: 10.1038/s42004-024-01341-w
Marvin Alberts, Teodoro Laino, Alain C. Vaucher
The application of machine learning models in chemistry has made remarkable strides in recent years. While analytical chemistry has received considerable interest from machine learning practitioners, its adoption into everyday use remains limited. Among the available analytical methods, Infrared (IR) spectroscopy stands out in terms of affordability, simplicity, and accessibility. However, its use has been limited to the identification of a selected few functional groups, as most peaks lie beyond human interpretation. We present a transformer model that enables chemists to leverage the complete information contained within an IR spectrum to directly predict the molecular structure. To cover a large chemical space, we pretrain the model using 634,585 simulated IR spectra and fine-tune it on 3,453 experimental spectra. Our approach achieves a top–1 accuracy of 44.4% and top–10 accuracy of 69.8% on compounds containing 6 to 13 heavy atoms. When solely predicting scaffolds, the model accurately predicts the top–1 scaffold in 84.5% and among the top–10 in 93.0% of cases. Infrared spectroscopy stands out as an analytical tool for its affordability, simplicity, and accessibility, however, its use has been limited to the identification of a select few functional groups, as most peaks lie beyond human interpretation. Here, the authors use a transformer model that enables chemists to leverage all information contained within an IR spectrum to directly predict the molecular structure.
{"title":"Leveraging infrared spectroscopy for automated structure elucidation","authors":"Marvin Alberts, Teodoro Laino, Alain C. Vaucher","doi":"10.1038/s42004-024-01341-w","DOIUrl":"10.1038/s42004-024-01341-w","url":null,"abstract":"The application of machine learning models in chemistry has made remarkable strides in recent years. While analytical chemistry has received considerable interest from machine learning practitioners, its adoption into everyday use remains limited. Among the available analytical methods, Infrared (IR) spectroscopy stands out in terms of affordability, simplicity, and accessibility. However, its use has been limited to the identification of a selected few functional groups, as most peaks lie beyond human interpretation. We present a transformer model that enables chemists to leverage the complete information contained within an IR spectrum to directly predict the molecular structure. To cover a large chemical space, we pretrain the model using 634,585 simulated IR spectra and fine-tune it on 3,453 experimental spectra. Our approach achieves a top–1 accuracy of 44.4% and top–10 accuracy of 69.8% on compounds containing 6 to 13 heavy atoms. When solely predicting scaffolds, the model accurately predicts the top–1 scaffold in 84.5% and among the top–10 in 93.0% of cases. Infrared spectroscopy stands out as an analytical tool for its affordability, simplicity, and accessibility, however, its use has been limited to the identification of a select few functional groups, as most peaks lie beyond human interpretation. Here, the authors use a transformer model that enables chemists to leverage all information contained within an IR spectrum to directly predict the molecular structure.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":5.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01341-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643905","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 : 2024-11-15DOI: 10.1038/s42004-024-01355-4
Lijuan Zhang, Ning Qi, Yuan Li, Xiao Wang, Lifei Zhang
Subduction zones metamorphic fluids are pivotal in geological events such as volcanic eruptions, seismic activity, mineralization, and the deep carbon cycle. However, the mechanisms governing carbon mobility in subduction zones remain largely unresolved. Here we present the first observations of immiscible H2O-CH4 fluids coexisting in retrograde carbonated eclogite from the Western Tianshan subduction zone, China. We identified two types of fluid inclusions in host ankerite and amphibole, as well as in garnet and omphacite. Type-1 inclusions are water-rich with CH4 vapor, whereas Type-2 are CH4-rich, with minimal or no H2O. The coexistence of these fluid types indicates the presence of immiscible fluid phases under high-pressure conditions (P = 1.3-2.1 GPa). Carbonates in subduction zones can effectively decompose through reactions with silicates, leading to the generation of abiotic CH4. Our findings suggest that substantial amounts of carbon could be transferred from the slab to mantle wedge as immiscible CH4 fluids. This process significantly enhances decarbonation efficiency and may contribute to the formation of natural gas deposits. The metamorphic fluids in subduction zone play a crucial role in geological events such as volcanic eruptions, seismic activity, mineralization and the deep carbon cycle. Here, the authors report on the coexistence of immiscible water and methane fluids in retrograde carbonated eclogite and identify two types of fluid inclusions in different host minerals, advancing our understanding of immiscible C-O-H fluids and their upwards migration in subducting slabs.
{"title":"Immiscible metamorphic water and methane fluids preserved in carbonated eclogite","authors":"Lijuan Zhang, Ning Qi, Yuan Li, Xiao Wang, Lifei Zhang","doi":"10.1038/s42004-024-01355-4","DOIUrl":"10.1038/s42004-024-01355-4","url":null,"abstract":"Subduction zones metamorphic fluids are pivotal in geological events such as volcanic eruptions, seismic activity, mineralization, and the deep carbon cycle. However, the mechanisms governing carbon mobility in subduction zones remain largely unresolved. Here we present the first observations of immiscible H2O-CH4 fluids coexisting in retrograde carbonated eclogite from the Western Tianshan subduction zone, China. We identified two types of fluid inclusions in host ankerite and amphibole, as well as in garnet and omphacite. Type-1 inclusions are water-rich with CH4 vapor, whereas Type-2 are CH4-rich, with minimal or no H2O. The coexistence of these fluid types indicates the presence of immiscible fluid phases under high-pressure conditions (P = 1.3-2.1 GPa). Carbonates in subduction zones can effectively decompose through reactions with silicates, leading to the generation of abiotic CH4. Our findings suggest that substantial amounts of carbon could be transferred from the slab to mantle wedge as immiscible CH4 fluids. This process significantly enhances decarbonation efficiency and may contribute to the formation of natural gas deposits. The metamorphic fluids in subduction zone play a crucial role in geological events such as volcanic eruptions, seismic activity, mineralization and the deep carbon cycle. Here, the authors report on the coexistence of immiscible water and methane fluids in retrograde carbonated eclogite and identify two types of fluid inclusions in different host minerals, advancing our understanding of immiscible C-O-H fluids and their upwards migration in subducting slabs.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01355-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636954","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}
To achieve sustainable resource circulation, preparation of reactive species from stable compounds is unavoidable. Chlorine chemistry is an eco-friendly methodology to address this demand. Chlorine is industrially produced from sodium chloride (NaCl), an abundant natural resource in oceans. Chlorine provides various chemical products, including polymers, through chlorination and subsequent conversion reactions. In these reactions, the byproducts are usually hydrogen chloride, which is commercially utilized as hydrochloric acid and is finally neutralized to NaCl after use. Therefore, chlorine chemistry enables fine chemical production from NaCl with almost no wastage. This review provides an overview of the synthesis of fine chemicals and polymers using chlorine chemistry and discusses them from the perspective of sustainability. To achieve sustainable resource circulation, preparation of reactive species from stable compounds is needed, and chlorine chemistry is an eco-friendly approach to address this need. Here, the authors provide an overview of the synthesis of fine chemicals and polymers using chlorine chemistry, with emphasis with regards to sustainability.
{"title":"Sustainable synthesis of fine chemicals and polymers using industrial chlorine chemistry","authors":"Yasuhiro Kohsaka, Daisuke Matsuura, Yoshikazu Kimura","doi":"10.1038/s42004-024-01345-6","DOIUrl":"10.1038/s42004-024-01345-6","url":null,"abstract":"To achieve sustainable resource circulation, preparation of reactive species from stable compounds is unavoidable. Chlorine chemistry is an eco-friendly methodology to address this demand. Chlorine is industrially produced from sodium chloride (NaCl), an abundant natural resource in oceans. Chlorine provides various chemical products, including polymers, through chlorination and subsequent conversion reactions. In these reactions, the byproducts are usually hydrogen chloride, which is commercially utilized as hydrochloric acid and is finally neutralized to NaCl after use. Therefore, chlorine chemistry enables fine chemical production from NaCl with almost no wastage. This review provides an overview of the synthesis of fine chemicals and polymers using chlorine chemistry and discusses them from the perspective of sustainability. To achieve sustainable resource circulation, preparation of reactive species from stable compounds is needed, and chlorine chemistry is an eco-friendly approach to address this need. Here, the authors provide an overview of the synthesis of fine chemicals and polymers using chlorine chemistry, with emphasis with regards to sustainability.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01345-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616111","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 : 2024-11-14DOI: 10.1038/s42004-024-01356-3
Davide Ciccarelli, Ben M. J. Lancaster, D. Christopher Braddock, Matteo Calvaresi, Miroslav Mišík, Siegfried Knasmüller, Edoardo Jun Mattioli, Francesco Zerbetto, Andrew J. P. White, Tim Marczylo, Timothy W. Gant, Leon P. Barron
The presence of two new disinfectant by-product (DBP) groups in the UK was recently shown using non-target analysis, halogenated-hydroxycyclopentenediones and halogenated-methanesulfonic acids. In this work, we confirmed the structure of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione (TBHCD), and quantified it together with dibromomethanesulfonic acid at 122 ± 34 and 326 ± 157 ng L−1 on average in London’s drinking water, respectively (n = 21). We found TBHCD to be photolabile and unstable in tap water and at alkaline pH. Furthermore, spectral and computational data for TBHCD and three other halogenated-hydroxycyclopentenediones indicated they could act as a source of radicals in water and in the body. Importantly, TBHCD was calculated to have a 14.5 kcal mol−1 lower C-Br bond dissociation enthalpy than the N-Br bond of N-bromosuccinimide, a common radical substitution reagent used in organic synthesis. TBHCD was mutagenic in Salmonella/microsome assays using strains TA98, TA100 and TA102. This work reveals the unique features, activity and toxicity of trihalogenated hydroxycyclopent-4-ene-1,3-diones, prompting a need to more comprehensively assess their risks. Halogenated disinfection by-products are a recognized health risk, but unequivocal identification and monitoring of new compounds is challenging, which prevents risk assessment. Here, the authors identify and quantify 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione in London drinking water, and describe the compound’s activity and toxicity.
{"title":"Structure confirmation, reactivity, bacterial mutagenicity and quantification of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione in drinking water","authors":"Davide Ciccarelli, Ben M. J. Lancaster, D. Christopher Braddock, Matteo Calvaresi, Miroslav Mišík, Siegfried Knasmüller, Edoardo Jun Mattioli, Francesco Zerbetto, Andrew J. P. White, Tim Marczylo, Timothy W. Gant, Leon P. Barron","doi":"10.1038/s42004-024-01356-3","DOIUrl":"10.1038/s42004-024-01356-3","url":null,"abstract":"The presence of two new disinfectant by-product (DBP) groups in the UK was recently shown using non-target analysis, halogenated-hydroxycyclopentenediones and halogenated-methanesulfonic acids. In this work, we confirmed the structure of 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione (TBHCD), and quantified it together with dibromomethanesulfonic acid at 122 ± 34 and 326 ± 157 ng L−1 on average in London’s drinking water, respectively (n = 21). We found TBHCD to be photolabile and unstable in tap water and at alkaline pH. Furthermore, spectral and computational data for TBHCD and three other halogenated-hydroxycyclopentenediones indicated they could act as a source of radicals in water and in the body. Importantly, TBHCD was calculated to have a 14.5 kcal mol−1 lower C-Br bond dissociation enthalpy than the N-Br bond of N-bromosuccinimide, a common radical substitution reagent used in organic synthesis. TBHCD was mutagenic in Salmonella/microsome assays using strains TA98, TA100 and TA102. This work reveals the unique features, activity and toxicity of trihalogenated hydroxycyclopent-4-ene-1,3-diones, prompting a need to more comprehensively assess their risks. Halogenated disinfection by-products are a recognized health risk, but unequivocal identification and monitoring of new compounds is challenging, which prevents risk assessment. Here, the authors identify and quantify 2,2,4-tribromo-5-hydroxycyclopent-4-ene-1,3-dione in London drinking water, and describe the compound’s activity and toxicity.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":5.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01356-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616105","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 : 2024-11-13DOI: 10.1038/s42004-024-01332-x
Ke-Jia Wu, Wen Sun, Jian-Min Sun, Chang Lu, Ning Sun, Chung‐Hang Leung, Yan Li, Chun Wu
The scarcity of suitable high-throughput screening technology for hydrogen sulfide (H2S) donors has hampered the discovery of H2S donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted H2S probe to monitor the real-time dynamic change of H2S. By using the time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor H2S in living cells with decreased false negative results. As a proof-of-concept, three natural products were identified as potential H2S donors from a natural product library using the developed TRES probe. Notably, the discovery of allicin and diallyl trisulfide demonstrated the feasibility of this screening platform, while garlic-derived allyl methyl sulfide was explored as a H2S donor candidate. The results were further validated by a commercial assay. We anticipate this high-throughput platform could facilitate the discovery of H2S donors by discriminating the endogenous interfering fluorescence from biological systems. H2S donors in living cells are essential for modulating H2S levels and have been proposed to be relevant for managing hepatic disorders, but conventional platforms to screen for H2S donors are plagued by interference by endogenous background fluorescence signals. Here, the authors develop a luminogenic probe—based on an Ir(III) complex with a 1,10-phenanthroline-5,6-dione moiety—capable of selective response to mitochondrial H2S, and set up an anti-interference high-throughput screening system capable of distinguishing target signals from complex background autofluorescence in living cells.
{"title":"An iridium(III) complex-based luminogenic probe for high-throughput screening of hydrogen sulfide donors in living cells","authors":"Ke-Jia Wu, Wen Sun, Jian-Min Sun, Chang Lu, Ning Sun, Chung‐Hang Leung, Yan Li, Chun Wu","doi":"10.1038/s42004-024-01332-x","DOIUrl":"10.1038/s42004-024-01332-x","url":null,"abstract":"The scarcity of suitable high-throughput screening technology for hydrogen sulfide (H2S) donors has hampered the discovery of H2S donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted H2S probe to monitor the real-time dynamic change of H2S. By using the time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor H2S in living cells with decreased false negative results. As a proof-of-concept, three natural products were identified as potential H2S donors from a natural product library using the developed TRES probe. Notably, the discovery of allicin and diallyl trisulfide demonstrated the feasibility of this screening platform, while garlic-derived allyl methyl sulfide was explored as a H2S donor candidate. The results were further validated by a commercial assay. We anticipate this high-throughput platform could facilitate the discovery of H2S donors by discriminating the endogenous interfering fluorescence from biological systems. H2S donors in living cells are essential for modulating H2S levels and have been proposed to be relevant for managing hepatic disorders, but conventional platforms to screen for H2S donors are plagued by interference by endogenous background fluorescence signals. Here, the authors develop a luminogenic probe—based on an Ir(III) complex with a 1,10-phenanthroline-5,6-dione moiety—capable of selective response to mitochondrial H2S, and set up an anti-interference high-throughput screening system capable of distinguishing target signals from complex background autofluorescence in living cells.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-7"},"PeriodicalIF":5.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01332-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616101","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 : 2024-11-13DOI: 10.1038/s42004-024-01360-7
Sam G. Lewis, Ben A. Coulson, Anna J. Warren, Mark R. Warren, Lauren E. Hatcher
The increasing availability of ultrabright Light Sources is facilitating the study of smaller crystals at faster timescales but with an increased risk of severe X-ray damage, leading to developments in multi-crystal methods such as serial crystallography (SX). SX studies on crystals with small unit cells are challenging as very few reflections are recorded in a single data image, making it difficult to determine the orientation matrix for each crystal and thus preventing the combination of the data from all crystals for structure solution. We herein present a Small-Rotative Fixed-Target Serial Synchrotron Crystallography (SR-FT-SSX) methodology, in which rotation of the serial target through a small diffraction angle $$(varphi )$$ at each crystal delivers high-quality data, facilitating ab initio unit cell determination and atomic-scale structure solution. The method is benchmarked using microcrystals of the small-molecule photoswitch sodium nitroprusside dihydrate, obtaining complete data to dmin = 0.6 Å by combining just 66 partial datasets selected against rigorous quality criteria. Multi-crystal methods such as serial crystallography can provide a complete 3D structure of the target material before radiation damage becomes significant, but the methods are challenging for small molecule crystals with small unit cells, where very few reflections are recorded in a single data image. Here, the authors present a small-rotative fixed-target serial synchrotron crystallography (SR-FT-SSX) methodology, in which rotation of the serial target through a small diffraction angle $$(varphi )$$ at each crystal delivers high-quality data, facilitating ab initio unit cell determination and atomic-scale structure solution.
超亮光源的日益普及有助于以更快的时间尺度研究更小的晶体，但同时也增加了严重 X 射线损伤的风险，这导致了多晶体方法的发展，如序列晶体学（SX）。对具有小单元晶胞的晶体进行 SX 研究具有挑战性，因为单个数据图像中记录的反射很少，难以确定每个晶体的取向矩阵，因此无法将所有晶体的数据结合起来进行结构求解。我们在此提出了一种小旋转固定目标串行同步辐射晶体学（SR-FT-SSX）方法，即在每个晶体上通过一个小衍射角（φ）旋转串行目标，从而获得高质量的数据，促进原子单胞的确定和原子尺度的结构求解。该方法以小分子光开关硝普钠二水合物的微晶为基准，通过合并根据严格质量标准选出的 66 个部分数据集，获得了 dmin = 0.6 Å 的完整数据。
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Pub Date : 2024-11-12DOI: 10.1038/s42004-024-01353-6
Suryakamal Sarma, Neha Thakur, Nidhi Varshney, Hem Chandra Jha, Tridib K. Sarma
The integration of biomolecules into supramolecular nanostructures forms the basis of the natural world. Naturally occurring liquid-liquid phase separation resulting in biomolecular condensates has inspired the formation of biomolecule-based smart materials with multi-dimensional applications. A non-covalent bio-condensation between biomass DNA and guanosine monophosphate (GMP) has been described, mimicking chromatin folding and creating a unique “all-nucleic” DNA-GMP condensates. These condensates initiate the formation of G-quadruplex-based superstructures, assembling into super-helical fibres driven by synergistic hydrogen bonding and stacking, which have been thoroughly investigated. This simple, one-step method for the bio-condensation of biomass DNA leads to an “all-nucleic” hydrogel with higher-order self-assembly and excellent mechanical properties. While most of the reported DNA based biomaterials, including hydrogels, require precisely sequenced and molecularly architectured DNA building blocks, we have developed a simple, universal, and facile bio-condensation method that utilizes biomass DNA acquired from any bio-resource to fabricate DNA hydrogels. The hydrogel efficiently encapsulates and sustains the release of both hydrophilic and hydrophobic drugs, demonstrating its competency as a drug carrier. We believe this energy-efficient and low-cost method represents a new technique for using biomass DNA as building blocks for the next generation of soft materials. Biomolecular condensates provide a useful platform for a range of applications. Here, the authors describe a non-covalent bio-condensation between biomass DNA and guanosine monophosphate, mimicking chromatin folding and creating an all-nucleic hydrogel as a carrier for both hydrophobic and hydrophilic drugs.
生物分子与超分子纳米结构的结合构成了自然界的基础。自然发生的液-液相分离产生的生物分子缩合物启发了多维应用的生物分子智能材料的形成。生物质 DNA 和单磷酸鸟苷（GMP）之间的非共价生物缩合已经得到描述，这种缩合模仿染色质折叠，形成了独特的 "全核 "DNA-GMP 缩合物。这些凝聚物开始形成基于 G-四链的超结构，在协同氢键和堆叠的驱动下组装成超螺旋纤维，并对其进行了深入研究。这种简单的生物质 DNA 生物缩合一步法可产生一种 "全核 "水凝胶，具有高阶自组装和优异的机械性能。大多数已报道的基于 DNA 的生物材料（包括水凝胶）都需要精确排序和分子结构化的 DNA 构建模块，而我们已经开发出一种简单、通用和方便的生物缩合方法，利用从任何生物资源中获取的生物质 DNA 来制造 DNA 水凝胶。这种水凝胶能有效地包裹和维持亲水性和疏水性药物的释放，证明了其作为药物载体的能力。我们相信，这种高能效、低成本的方法代表了一种利用生物 DNA 作为下一代软材料构件的新技术。生物分子凝聚物为一系列应用提供了有用的平台。在这里，作者描述了生物质 DNA 与单磷酸鸟苷之间的非共价生物缩合，模仿染色质折叠，创造出全核水凝胶，作为疏水性和亲水性药物的载体。
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