ACS Central Science最新文献_第10页

Unveiling the Structure of Anhydrous Sodium Valproate with 3D Electron Diffraction and a Facile Sample Preparation Workflow. 用三维电子衍射揭示无水丙戊酸钠的结构和简单的样品制备流程。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-21 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00412

Jiaoyan Xu, Vivek Srinivas, Rohit Kumar, Laura Pacoste, Yiwang Guo, Taimin Yang, Changquan Calvin Sun, Martin Högbom, Xiaodong Zou, Hongyi Xu

{"title":"Unveiling the Structure of Anhydrous Sodium Valproate with 3D Electron Diffraction and a Facile Sample Preparation Workflow.","authors":"Jiaoyan Xu, Vivek Srinivas, Rohit Kumar, Laura Pacoste, Yiwang Guo, Taimin Yang, Changquan Calvin Sun, Martin Högbom, Xiaodong Zou, Hongyi Xu","doi":"10.1021/acscentsci.5c00412","DOIUrl":"10.1021/acscentsci.5c00412","url":null,"abstract":"Understanding the structure of an active pharmaceutical ingredient is essential for gaining insights into its physicochemical properties. Sodium valproate, one of the most effective antiepileptic drugs, was first approved for medical use in 1967. However, the structure of its anhydrous form has remained unresolved. This is because it was difficult to grow crystals of sufficient size for single-crystal X-ray diffraction (SCXRD). Although 3D electron diffraction (3D ED) can be used for studying crystals that are too small for SCXRD, the crystals of anhydrous sodium valproate are extremely sensitive to both humidity and electron beams. They degrade quickly both in air and under an electron beam at room temperature. In this study, we developed a glovebox-assisted cryo-transfer workflow for the preparation of EM grids in a protected atmosphere to overcome the current challenges for studying air- and beam-sensitive samples using 3D ED. Using this technique, we successfully determined the structure of anhydrous sodium valproate, revealing the formation of Na-valproate polyhedral chains. Our results provide a robust framework for the 3D ED analysis of air-sensitive crystals, greatly enhancing its utility across various scientific disciplines.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"960-966"},"PeriodicalIF":12.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Conversation with Elaine Bearer, Neuropathologist. 与神经病理学家Elaine Bearer的对话。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-19 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00840

Louisa Dalton

引用次数: 0

In Crystallo Photochemistry: Reimagining Synthetic Tractability with Transparent Single-Crystalline Flasks. 晶体光化学：用透明的单晶烧瓶重新想象合成的可追溯性。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-19 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00549

Aishanee Sur, David C Powers

{"title":"In Crystallo Photochemistry: Reimagining Synthetic Tractability with Transparent Single-Crystalline Flasks.","authors":"Aishanee Sur, David C Powers","doi":"10.1021/acscentsci.5c00549","DOIUrl":"10.1021/acscentsci.5c00549","url":null,"abstract":"Expanding the boundaries of synthetic tractability  of what molecules can be synthesized and isolated  is an eternal challenge for synthetic chemists. The development of new synthetic methods and strategies enables the properties and potential functions of novel molecular targets to be experimentally evaluated. In the context of catalysis, predictable synthetic strategies are often available to access kinetically persistent intermediates such as catalyst resting states. In contrast, synthesis and characterization of the reactive intermediates are often not possible due to the fleeting lifetimes of these species. In crystallo photochemistry combines single-crystal matrix isolation with cryogenic photochemistry to enable reactive intermediates to be synthesized under conditions in which they are persistent and can be (crystallographically) characterized. This Outlook highlights key achievements of in crystallo photochemistry as well as discusses opportunities and challenges that confront realization of the potential of in crystallo synthesis to redefine the boundaries of synthetic tractability.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"834-842"},"PeriodicalIF":12.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multicatalysis-Enabled Multicomponent Reactions Generate a PTP1B Inhibitor. 多催化多组分反应生成PTP1B抑制剂。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-19 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00041

Taoda Shi, Yukai Li, Jiying Yang, Weining Weng, Mengchu Zhang, Jirong Shu, Yu Qian, Tianyuan Zhang, Wenhao Hu

{"title":"Multicatalysis-Enabled Multicomponent Reactions Generate a PTP1B Inhibitor.","authors":"Taoda Shi, Yukai Li, Jiying Yang, Weining Weng, Mengchu Zhang, Jirong Shu, Yu Qian, Tianyuan Zhang, Wenhao Hu","doi":"10.1021/acscentsci.5c00041","DOIUrl":"10.1021/acscentsci.5c00041","url":null,"abstract":"Multicomponent reactions are powerful tools for expanding the chemical space in drug discovery, yet achieving selectivity remains a formidable challenge. Here, we introduce a multicatalytic strategy to enable a multicomponent reaction, utilizing a cooperative system of rhodium, copper, Brønsted acid, and magnesium catalysts. This approach achieves excellent chemo-, diastereo-, and enantioselectivity (up to 99% yield, >20:1 dr, and 99% ee). Mechanistic studies, combining experimental and computational analyses, reveal a cascade sequence involving cyclopropenation, desilylation, cyclization, isomerization, aldol addition, and hydrolysis. This highly selective method exhibits broad substrate generality, producing 50 diverse CHBOs. Virtual screening and rapid biological evaluation led to the discovery of (S, S)-3ak, a potent PTP1B inhibitor with a submicromolar IC50 value. Notably, (S, S)-3ak demonstrated 3-fold higher potency than its enantiomer, underscoring the critical role of chirality. Molecular docking studies elucidated the enantioselective binding mechanism, revealing key interactions responsible for activity differences. In summary, this MMCR strategy enables efficient access to enantiopure bioactive molecules and facilitates drug discovery, exemplified by a novel chiral PTP1B inhibitor.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"938-949"},"PeriodicalIF":12.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Submolecular Resolution of β‑Sheet Plasticity: Decoding Mutations and PTMs in Protein Aggregation Disorders. β -薄片可塑性的亚分子分辨率：解码突变和PTMs在蛋白质聚集障碍。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-16 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00421

Ruonan Wang, Zhongyi Jian, Yanlian Yang, Chen Wang, Lanlan Yu, Mingzhan Wang, Chenxuan Wang

{"title":"Submolecular Resolution of β‑Sheet Plasticity: Decoding Mutations and PTMs in Protein Aggregation Disorders.","authors":"Ruonan Wang, Zhongyi Jian, Yanlian Yang, Chen Wang, Lanlan Yu, Mingzhan Wang, Chenxuan Wang","doi":"10.1021/acscentsci.5c00421","DOIUrl":"10.1021/acscentsci.5c00421","url":null,"abstract":"The functional diversity of proteins often arises from the remodeling of conformational ensembles, particularly through mutations and post-translational modifications (PTMs). However, experimentally characterizing such ensembles remains challenging due to their heterogeneous and transient nature. Here, we report the determination of the conformational substates of β-sheets and the effect associated with mutations and PTMs in human islet amyloid polypeptide (hIAPP) via scanning tunneling microscopy (STM). Thanks to the ultrahigh resolution of STM, the β-sheets formed by the assembly of hIAPP were revealed to be conformationally diverse, including 17 types of conformational substates concomitant with 60 types of interconformation interactions. These conformational substates are highly heterogeneous in the folding structures but close in energy. Four mutations and PTMs were carried out with hIAPP to investigate the evolvability of the β-sheet assembly. Regulation effects accomplished by the mutations and PTMs on the conformational ensembles of β-sheets have been identified, including the number of conformational substates, the most probable substates, and the topography of the energetic landscapes of inter-β-strand interactions. Different types of variations show divergence in the influences on the β-sheet conformational ensembles, which is correlated with the divergent aggregation propensity. Our results highlight the plasticity of conformational ensembles upon mutations and PTMs.","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 6","pages":"927-937"},"PeriodicalIF":12.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Conversation with Matthias Rillig, Soil Ecologist 与土壤生态学家Matthias Rillig的对话

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-14 DOI: 10.1021/acscentsci.5c0081310.1021/acscentsci.5c00813

Katarina Zimmer,

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A Conversation with Matthias Rillig, Soil Ecologist. 与土壤生态学家Matthias Rillig的对话。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-14 eCollection Date: 2025-05-28 DOI: 10.1021/acscentsci.5c00813

Katarina Zimmer

引用次数: 0

Late-Stage Heteroarene Alkylation via Minisci Reaction with Gaseous Alkanes Enabled by Hydrogen Atom Transfer in Flow. 流动中氢原子转移使杂芳烃与气态烷烃的微反应后期烷基化。

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-13 eCollection Date: 2025-06-25 DOI: 10.1021/acscentsci.5c00468

Prakash Chandra Tiwari, Antonio Pulcinella, Emil Hodžić, Timothy Noël

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Pollution Confuses Pollinators. Can Scientists Retrain Them? 污染迷惑了传粉者。科学家能重新训练它们吗？

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-12 eCollection Date: 2025-05-28 DOI: 10.1021/acscentsci.5c00779

Marta Zaraska

引用次数: 0

Pollution Confuses Pollinators. Can Scientists Retrain Them? 污染迷惑了传粉者。科学家能重新训练它们吗？

IF 12.7 1区化学

ACS Central Science Pub Date : 2025-05-12 DOI: 10.1021/acscentsci.5c0077910.1021/acscentsci.5c00779

Marta Zaraska,

引用次数: 0