Communications Chemistry最新文献_第7页

A nonclassical pathway of β-hematin crystal nucleation enables its suppression by antimalarials. β-血红蛋白结晶成核的非经典途径使其能够被抗疟药物抑制。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-13 DOI: 10.1038/s42004-025-01612-0

Wenchuan Ma, Lakshmanji Verma, Huan-Jui Lee, Weichun Pan, Michael B Sherman, David J Sullivan, Jeffrey D Rimer, Jeremy C Palmer, Peter G Vekilov

{"title":"A nonclassical pathway of β-hematin crystal nucleation enables its suppression by antimalarials.","authors":"Wenchuan Ma, Lakshmanji Verma, Huan-Jui Lee, Weichun Pan, Michael B Sherman, David J Sullivan, Jeffrey D Rimer, Jeremy C Palmer, Peter G Vekilov","doi":"10.1038/s42004-025-01612-0","DOIUrl":"10.1038/s42004-025-01612-0","url":null,"abstract":"Organic biocrystals support essential functions or drive pathologies in numerous living organisms. Here we focus on the nucleation of hematin crystals, which form in malaria parasites as a part of their heme detoxification pathway. Suppression of hematin crystal nucleation has proven the most productive strategy to treat malaria, yet little is known about the relevant molecular mechanisms. We show that crystal nucleation can be suppressed and fine-tuned via the properties of a population of precursors that host nonclassical hematin crystal nucleation. The addition of modifiers selectively invokes one of three outcomes: suppressed nucleation, faster nucleation, or no effect. We demonstrate that β-hematin crystal nuclei form within mesoscopic hematin-rich clusters and that the impacts of the modifiers on crystal nucleation parallel their activity towards the nucleation precursors. Molecular simulations reveal that modifiers' activities derive from their interactions with the hematin monomers, dimers, and larger agglomerates. Collectively, these observations support a general method to control crystal nucleation that relies on solute-modifier interactions and their consequences for the nucleation precursors. The proposed rationale offers a powerful tool to control nucleation in areas that employ tailored crystalline materials and helps to understand how crystal assemblies with elaborate superstructures appear in nature.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"246"},"PeriodicalIF":6.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844805","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}

引用次数: 0

Supramolecular chiral inversion and regulation of phenylalanine-based organogels in low-polarity achiral solvents. 苯基丙氨酸有机凝胶在低极性非手性溶剂中的超分子手性反转和调控。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-12 DOI: 10.1038/s42004-025-01650-8

Wannian Zhang, Fang Yu, Yu-Peng He

{"title":"Supramolecular chiral inversion and regulation of phenylalanine-based organogels in low-polarity achiral solvents.","authors":"Wannian Zhang, Fang Yu, Yu-Peng He","doi":"10.1038/s42004-025-01650-8","DOIUrl":"10.1038/s42004-025-01650-8","url":null,"abstract":"Metamaterials with supramolecular chirality have been widely developed in many fields, and their assembly modes provide valuable insights for understanding living systems. In this work, we achieved for the first time the inversion of supramolecular chirality in organogels using a low-polarity achiral solvent. Furthermore, the regulation of supramolecular chirality was achieved through structural modification of the achiral moieties. Additionally, the impact of hydrogen bond variability on the modulation of supramolecular chirality was investigated by replacing the O atom with the N atom. Subsequently, the mechanisms governing supramolecular chirality modulation through low-polarity solvents and weakly polar structural motifs was elucidated. The results demonstrate that weak-polarity solvents, achiral long-chain moieties, and hydrogen bonds can individually serve as effective modulators for regulating intermolecular assembly patterns, thereby exerting critical influence on the emergence of supramolecular chirality. These findings establish a robust foundation for the precise construction and manipulation of supramolecular chirality in organogel systems.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"243"},"PeriodicalIF":6.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834317","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}

引用次数: 0

Investigation of a squaramide motif as a bioisostere of the amino-acid group of S-adenosyl-L-methionine and its functional impact on RNA methylation. 角酰胺基序作为s -腺苷- l-蛋氨酸氨基酸基生物同分异构体的研究及其对RNA甲基化的功能影响。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-12 DOI: 10.1038/s42004-025-01627-7

Jianxun Du, Batoul Mahcene, Valerii Martynov, Elisa Frezza, Christelle Vasnier, Luc Ponchon, Dylan Coelho, Frédéric Bonhomme, Emmanuelle Braud, Mélanie Etheve-Quelquejeu, Bruno Sargueil

{"title":"Investigation of a squaramide motif as a bioisostere of the amino-acid group of S-adenosyl-L-methionine and its functional impact on RNA methylation.","authors":"Jianxun Du, Batoul Mahcene, Valerii Martynov, Elisa Frezza, Christelle Vasnier, Luc Ponchon, Dylan Coelho, Frédéric Bonhomme, Emmanuelle Braud, Mélanie Etheve-Quelquejeu, Bruno Sargueil","doi":"10.1038/s42004-025-01627-7","DOIUrl":"10.1038/s42004-025-01627-7","url":null,"abstract":"Methyltransferases (MTases) are enzymes that methylate biomolecules like proteins, DNA, RNA, lipids, and small molecules, mostly using S-adenosyl-L-methionine (SAM) as a methyl donor. MTases have emerged as promising drug targets, and SAM analogues are widely employed to investigate their involvement in diseases and to develop effective drug therapies. We designed and synthesized stable SAM analogues with a squaramide moiety mimicking the methionine side chain. These compounds were tested on the two human m⁶A RNA MTases METTL3/14 and METTL16. While these SAM analogues failed to support catalytic activity, they exhibited potent inhibitory effects on the METTL3/14 activity. Surprisingly, some of these compounds demonstrated remarkable potency (KI = 3 nM) and specificity, likely attributed to the unique properties of the squaramide motif. Docking studies showed they bind METTL3/14 cofactor pocket similarly to SAM, allowing us to make new hypothesis on the catalytic mechanism. Our synthetic method expands the structural diversity of SAM analogues, providing a foundation for developing selective RNA MTase inhibitors.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"244"},"PeriodicalIF":6.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834315","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}

引用次数: 0

Structure-based rational design of covalent probes. 基于结构的共价探针合理设计。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-12 DOI: 10.1038/s42004-025-01606-y

Matthew Holcomb, Manuel Llanos, Althea Hansel-Harris, Stefano Forli

引用次数: 0

Quality Evaluation Based Simulation Selection (QEBSS) for analysis of conformational ensembles and dynamics of multidomain proteins. 基于质量评价的模拟选择（QEBSS）用于分析多结构域蛋白质的构象集成和动力学。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-10 DOI: 10.1038/s42004-025-01623-x

Amanda E Sandelin, Ricky Nencini, Ekrem Yasar, Satoshi Fudo, Vassilis Stratoulias, Tommi Kajander, O H Samuli Ollila

{"title":"Quality Evaluation Based Simulation Selection (QEBSS) for analysis of conformational ensembles and dynamics of multidomain proteins.","authors":"Amanda E Sandelin, Ricky Nencini, Ekrem Yasar, Satoshi Fudo, Vassilis Stratoulias, Tommi Kajander, O H Samuli Ollila","doi":"10.1038/s42004-025-01623-x","DOIUrl":"10.1038/s42004-025-01623-x","url":null,"abstract":"Multidomain proteins containing both folded and intrinsically disordered regions are crucial for biological processes, but characterizing their conformational ensembles and dynamics remains challenging. We introduce the Quality Evaluation Based Simulation Selection (QEBSS) protocol, which combines MD simulations with NMR-derived protein backbone 15N T1 and T2 spin relaxation times and hetNOE values to interpret conformational ensembles and dynamics of multidomain proteins. We demonstrate the practical advantage of QEBSS by characterizing four flexible multidomain proteins: calmodulin, EN2, MANF, and CDNF. These biologically important proteins have been difficult to study due to their flexible nature. Our findings reveal new insights into their conformational landscapes and dynamics, providing mechanistic understanding of their biological functions. QEBSS offers quantitative quality evaluation of simulations and a systematic approach for resolving conformational ensembles of multidomain proteins with heterogeneous dynamics. Given the importance of such proteins in biology, biotechnology, and materials science, QEBSS should benefit fields from drug design to novel materials development.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"241"},"PeriodicalIF":6.2,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811903","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}

引用次数: 0

Isolation of kinetically-stabilised diarylchalcogenide radical cations. 动力学稳定二芳基硫系自由基阳离子的分离。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-09 DOI: 10.1038/s42004-025-01613-z

Pascal Komorr, Corina Stoian, Aleksa Radović, Björn A Meyer, Pim Puylaert, George E Cutsail Iii, Emanuel Hupf, Jens Beckmann

{"title":"Isolation of kinetically-stabilised diarylchalcogenide radical cations.","authors":"Pascal Komorr, Corina Stoian, Aleksa Radović, Björn A Meyer, Pim Puylaert, George E Cutsail Iii, Emanuel Hupf, Jens Beckmann","doi":"10.1038/s42004-025-01613-z","DOIUrl":"10.1038/s42004-025-01613-z","url":null,"abstract":"Chalcogenide radical cations [R2E]•+ (E = S, Se, Te) are commonly short-lived intermediates of fundamental interest. Sulfide radical cations in particular are associated in vivo with oxidative stress and neuropathological processes. Having succeeded in the preparation of meta-terphenyl-based dichalcogenide radical cations [R2E2]•+ (E = S, Se, Te), and a telluride analogue [R2Te]•+ in the past, we aimed to complete the series regarding sulfur and selenium. Here we report on the single-electron oxidation of diarylchalcogenides MSFluindPhE (E = S, Se, Te; MSFluind = dispiro[fluorene-9,3'-(1',1',7',7'-tetramethyl-s-hydrindacen-4'-yl)-5',9\"-fluorene]) using XeF2 in the presence of K[B(C6F5)4], which afforded deeply coloured and isolable radical cation salts [MSFluindPhE][B(C6F5)4] (E = S, Se, Te). Structural and electronic properties were characterised by electron paramagnetic spectroscopy, cyclic voltammetry, optical absorption spectroscopy and single crystal X-ray diffraction (E = Se, Te), combined with extensive quantum mechanical computations.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"239"},"PeriodicalIF":6.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811902","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}

引用次数: 0

The ionic and protonation states of flavin control the activation and recovery of Drosophila cryptochrome. 黄素的离子态和质子化态控制着果蝇隐色素的激活和恢复。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-09 DOI: 10.1038/s42004-025-01647-3

Wenlong Xie, Mengqi Wan, Yuting Dai, Yingjun Jiang, Mohan Wang, Lili Zhou, Li Zhang, Linmei Sun, Xiaoyu Feng, Tian Xia, Bin Wen, Jun Lv, Xiuxiu Wang, Lei Xu

{"title":"The ionic and protonation states of flavin control the activation and recovery of Drosophila cryptochrome.","authors":"Wenlong Xie, Mengqi Wan, Yuting Dai, Yingjun Jiang, Mohan Wang, Lili Zhou, Li Zhang, Linmei Sun, Xiaoyu Feng, Tian Xia, Bin Wen, Jun Lv, Xiuxiu Wang, Lei Xu","doi":"10.1038/s42004-025-01647-3","DOIUrl":"10.1038/s42004-025-01647-3","url":null,"abstract":"Drosophila cryptochrome (dCry) is a flavin-containing photoreceptor. The release of C-terminal tail (CTT) upon illumination is a crucial step for the light sensing of dCry. Here, we demonstrated that both anionic semiquinone (asq) and anionic hydroquinone (hq) triggered CTT release, while neutral semiquinone (nsq) formation suppressed it. However, during photoreduction, a fraction of nsq was formed in dCry under neutral conditions, and the fraction of which increased when the pH decreased. The proton required for nsq formation might be transferred to flavin through a side tunnel. The nsq formation was minimized in dCry under basic conditions, or in the mutants in CTT, which resulted in enhanced CTT release but slower oxidation (i.e. recovery) after photoreduction. Therefore, forming a proper fraction of nsq is important for fast recovery of dCry after light sensing. Nevertheless, a key residue at the side tunnel, His378, is a proton interceptor that adjusts the nsq formation.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"240"},"PeriodicalIF":6.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811904","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}

引用次数: 0

Synthesis and characterization of crystalline polymeric carbonic acid (H₂CO₃) with sp³-hybridized carbon at elevated pressures. 高压下sp3杂化碳结晶聚合碳酸（H2CO3）的合成与表征。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-08 DOI: 10.1038/s42004-025-01614-y

Dominik Spahr, Lkhamsuren Bayarjargal, Lukas Brüning, Valentin Kovalev, Lena M Wedek, Maxim Bykov, Victor Milman, Nico Giordano, Björn Winkler, Elena Bykova

{"title":"Synthesis and characterization of crystalline polymeric carbonic acid (H2CO3) with sp3-hybridized carbon at elevated pressures.","authors":"Dominik Spahr, Lkhamsuren Bayarjargal, Lukas Brüning, Valentin Kovalev, Lena M Wedek, Maxim Bykov, Victor Milman, Nico Giordano, Björn Winkler, Elena Bykova","doi":"10.1038/s42004-025-01614-y","DOIUrl":"10.1038/s42004-025-01614-y","url":null,"abstract":"The existence of polymeric carbonic acid (H2CO3) at elevated pressures has been predicted, but has not been investigated experimentally. Here, polymeric carbonic acid containing sp3-hybridized carbon was synthesized and characterized at ≈40 GPa. H2CO3 single crystals were obtained by laser-heating a H2O + CO2 mixture in a diamond anvil cell. The orthorhombic crystal structure (Cmc21 with Z = 4) was refined from synchrotron single crystal X-ray diffraction data and is in agreement with a structural model predicted earlier. The crystal structure of H2CO3-Cmc21 is characterized by <math> <msup> <mrow><mrow><mo>[</mo> <mrow> <msub><mrow><mi>CO</mi></mrow> <mrow><mn>4</mn></mrow> </msub> </mrow> <mo>]</mo></mrow> </mrow> <mrow><mn>4</mn> <mo>-</mo></mrow> </msup> </math> building blocks which are connected via corner sharing, forming chains along the c-axis. The combination of single crystal X-ray data with experimental Raman spectroscopy and DFT-calculations confirms that the structural model of H2CO3-Cmc21 is appropriate. The synthesis condition of polymeric carbonic acid points towards its potential existence in ice giants including the ones present in our solar system.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"237"},"PeriodicalIF":6.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803808","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}

引用次数: 0

Optimizing drug design by merging generative AI with a physics-based active learning framework. 通过将生成式人工智能与基于物理的主动学习框架相结合来优化药物设计。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-08 DOI: 10.1038/s42004-025-01635-7

Isaac Filella-Merce, Alexis Molina, Lucía Díaz, Marek Orzechowski, Yamina A Berchiche, Yang Ming Zhu, Júlia Vilalta-Mor, Laura Malo, Ajay S Yekkirala, Soumya Ray, Victor Guallar

{"title":"Optimizing drug design by merging generative AI with a physics-based active learning framework.","authors":"Isaac Filella-Merce, Alexis Molina, Lucía Díaz, Marek Orzechowski, Yamina A Berchiche, Yang Ming Zhu, Júlia Vilalta-Mor, Laura Malo, Ajay S Yekkirala, Soumya Ray, Victor Guallar","doi":"10.1038/s42004-025-01635-7","DOIUrl":"10.1038/s42004-025-01635-7","url":null,"abstract":"Machine learning is transforming drug discovery, with generative models (GMs) gaining attention for their ability to design molecules with specific properties. However, GMs often struggle with target engagement, synthetic accessibility, or generalization. To address these, we developed a GM workflow integrating a variational autoencoder with two nested active learning cycles. These iteratively refine their predictions using chemoinformatics and molecular modeling predictors. We tested our workflow on two systems, CDK2 and KRAS, successfully generating diverse, drug-like molecules with high predicted affinity and synthesis accessibility. Notably, we generated novel scaffolds distinct from those known for each target. For CDK2, we synthetized 9 molecules yielding 8 with in vitro activity, including one with nanomolar potency. For KRAS, in silico methods validated by CDK2 assays identified 4 molecules with potential activity. These findings showcase our GM workflow's ability to explore novel chemical spaces tailored for specific targets, thereby opening new avenues in drug discovery.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"238"},"PeriodicalIF":6.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803807","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}

引用次数: 0

Advanced architectures of electrochemical interfaces. 电化学界面的先进结构。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-07 DOI: 10.1038/s42004-025-01633-9

Wei Zhang, Andrea Paolella, Maria-Magdalena Titirici, Takashi Tsuchiya

引用次数: 0