{"title":"Selective arylation of atypical C-F bonds in polyfluoroarenes with aryl chlorides.","authors":"Zhi Liu,Chaoyu Du,Jie Han,Xiaoliang Yang,Siyu Xia,Kai Liu,Chengjian Zhu,Weipeng Li,Jin Xie","doi":"10.1038/s41557-025-01962-1","DOIUrl":"https://doi.org/10.1038/s41557-025-01962-1","url":null,"abstract":"Selective activation of specific C-F bonds in polyfluoroarenes represents a challenge in transition metal catalysis. Here we report a photoexcited nickel-catalysed cross-electrophile coupling between polyfluoroarenes and aryl chlorides, achieving highly selective arylation at atypical C-F sites of fluoroarenes, facilitated by a synergistic lithium salt effect. A wide range of structurally diverse fluorine-containing biaryls are obtained in 33-94% yields with satisfying C-F regioselectivity. Notably, the observed regioselectivity is atypical and complements existing methodologies, such as palladium-catalysed and visible-light photoredox-catalysed defluorinative functionalization reactions. Our mechanistic studies and theoretical calculations suggest that the lithium salt could interact with both pentafluorobenzene and the Ni catalyst, effectively lowering the energy barrier and modulating the regioselectivity. The synthetic versatility of our approach is underscored by late-stage synthetic application and sequential functionalization of multiple C-F bonds, which further demonstrates its robust utility in concisely constructing partially fluorinated and biologically interesting compounds.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"121 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Divergent access to E- or Z-trisubstituted medium-sized cycloalkenes by Pd-catalysed cycloaddition.","authors":"Gong-Feng Zou,Wenxuan Lin,Lin Shi,Bin-Miao Yang,Yu Lan,Yu Zhao","doi":"10.1038/s41557-025-01933-6","DOIUrl":"https://doi.org/10.1038/s41557-025-01933-6","url":null,"abstract":"Despite their significance in nature, medium-sized rings (particularly 9-11 membered ones) are non-existent in commercial small-molecule drugs largely due to the lack of efficient syntheses. Even with the widespread presence of macrocyclic alkenes in therapeutic agents, stereoselective access to either E- or Z-alkenes remains a formidable challenge. The few available methods for stereoselective macrocyclic alkene synthesis necessitate the use of geometrically pure E- or Z-alkene starting materials. Here we report the construction of 11-membered heterocyclic alkenes through Pd-catalysed formal cycloaddition of two readily available building blocks. This catalytic method also achieves a ligand-induced catalytic divergent preparation of either E- or Z-trisubstituted cycloalkenes starting from common terminal alkene substrates. Density functional theory calculations establish that the key alkoxide-chelated Pd-π-allyl intermediate adopts η1 or η3 coordination depending on the ligand used. This leads to allylic substitution using opposite π-allyl faces and in turn E- or Z-geometry in the cycloalkene products.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"86 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature chemistryPub Date : 2025-10-03DOI: 10.1038/s41557-025-01951-4
David D O'Regan
{"title":"Icing a three-layer cake for predictive modelling of adsorption.","authors":"David D O'Regan","doi":"10.1038/s41557-025-01951-4","DOIUrl":"https://doi.org/10.1038/s41557-025-01951-4","url":null,"abstract":"","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"78 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature chemistryPub Date : 2025-10-03DOI: 10.1038/s41557-025-01957-y
Michelle Francl
{"title":"Opinionated science","authors":"Michelle Francl","doi":"10.1038/s41557-025-01957-y","DOIUrl":"10.1038/s41557-025-01957-y","url":null,"abstract":"When the facts can’t speak for themselves, scientists can give them a voice, argues Michelle Francl.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 10","pages":"1435-1436"},"PeriodicalIF":20.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature chemistryPub Date : 2025-10-03DOI: 10.1038/s41557-025-01964-z
Priscila Vensaus
{"title":"A magnetic push for electrolysis in space.","authors":"Priscila Vensaus","doi":"10.1038/s41557-025-01964-z","DOIUrl":"https://doi.org/10.1038/s41557-025-01964-z","url":null,"abstract":"","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"157 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature chemistryPub Date : 2025-10-03DOI: 10.1038/s41557-025-01924-7
Yasuhisa Mizutani
{"title":"Harnessing light the retinal way","authors":"Yasuhisa Mizutani","doi":"10.1038/s41557-025-01924-7","DOIUrl":"10.1038/s41557-025-01924-7","url":null,"abstract":"Yasuhisa Mizutani marvels at how effectively nature utilizes the π-conjugated system of retinal in proteins.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 10","pages":"1618-1618"},"PeriodicalIF":20.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature chemistryPub Date : 2025-10-03DOI: 10.1038/s41557-025-01965-y
Guanming Lao,Taras Khvorost,Antonio Macias,Harry W T Morgan,Robert H Lavroff,Ryan Choi,Haowen Zhou,Denis Usvyat,Guo-Zhu Zhu,Miguel A García-Garibay,Anastassia N Alexandrova,Eric R Hudson,Wesley C Campbell
{"title":"Bottom-up approach to making larger hydrocarbon molecules capable of optical cycling.","authors":"Guanming Lao,Taras Khvorost,Antonio Macias,Harry W T Morgan,Robert H Lavroff,Ryan Choi,Haowen Zhou,Denis Usvyat,Guo-Zhu Zhu,Miguel A García-Garibay,Anastassia N Alexandrova,Eric R Hudson,Wesley C Campbell","doi":"10.1038/s41557-025-01965-y","DOIUrl":"https://doi.org/10.1038/s41557-025-01965-y","url":null,"abstract":"Molecules capable of repeatable, narrow-band spontaneous photon scattering are prized for direct laser cooling and quantum state detection. Recently, large molecules incorporating phenyl rings have been shown to exhibit a high probability of returning to the same vibrational state after photon emission, a behaviour previously observed in small molecules, although it is not yet known if the high vibrational-mode density of even larger species will eventually compromise optical cycling. Here we systematically increase the size of hydrocarbon ligands attached to single alkaline-earth phenoxides from -H to -C14H19 while measuring the vibrational branching fractions of the optical transition. We find that varying the ligand size from one to more than 30 atoms does not systematically reduce the cycle closure, which remains around 90%. Theoretical extensions to larger diamondoids and diamond surfaces suggest that alkaline-earth phenoxides may maintain their desirable scattering behaviour as the system size grows further, with no indication of an upper limit.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"26 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pseudokinases can catalyse peptide cyclization through thioether crosslinking.","authors":"Ling Hu, Miao Li, Yueqian Sang, Chengxin Zhao, Jiwu Huang, Wei Huang, Yanqing Xue, Lei Liu, Yucheng Gu, Pengchen Ma, Xiao-Song Xue, Lifeng Pan, Wen Liu","doi":"10.1038/s41557-025-01954-1","DOIUrl":"https://doi.org/10.1038/s41557-025-01954-1","url":null,"abstract":"<p><p>The protein-kinase-like superfamily proteins are crucial and generally catalyse substrate phosphorylation using adenosine 5'-triphosphate. Pseudokinases are non-canonical protein-kinase-like members deficient in kinase activity, and few of them are known to be enzymatically active and to have catalytic ability rather than phosphorylation. Based on biosynthetic investigations into thioamitides and lanthipeptides-two different families of ribosomally synthesized and post-translationally modified peptides-we here report a peptide cyclization activity of pseudokinases (TvaE and SacE) that enables (ene)thioether residue formation. We determine the dedicated cyclase activity in unsaturated 2-aminovinyl-cysteine formation and mine for similar activity in saturated lanthionine formation. Biochemical characterization, heterologous expression, co-crystallization, computational analysis, genome mining, isotope labelling and site-specific mutagenesis rationalize the commonality in catalysis, demonstrating that a protein-kinase fold can be repurposed for unexpected utilities. Related cyclases differ from known enzymatically active pseudokinases that resemble canonical protein-kinase-like proteins in mechanism and function. Instead, they catalyse Michael addition for (ene)thioether crosslinking through a sandwich-like substrate-assisted process.</p>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":" ","pages":""},"PeriodicalIF":20.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A two-metalloenzyme cascade constructs the azetidine-containing pharmacophore.","authors":"Rong Gong,Yao Qu,Jia Liu,Xuan Zhang,Liwei Zhou,Zhu Tian,Xinyue Zeng,Boyu Jin,Zhen Li,Le Yu,Ruyi Chen,Yang Zhou,Langxing Liao,Liulin Yang,Xuemin Song,You-Sheng Cai,Kun Shen,Zixin Deng,Zhengyu Zhang,Binju Wang,Wenqing Chen","doi":"10.1038/s41557-025-01949-y","DOIUrl":"https://doi.org/10.1038/s41557-025-01949-y","url":null,"abstract":"Azetidine is a prominent pharmacophore present in dozens of drug-related molecules of both natural and synthetic origins. But how nature builds this moiety has long remained enigmatic. Here we address the full deciphering of a two-metalloenzyme cascade leading to polyoximic acid, an azetidine-containing moiety of the fungicide polyoxin. We demonstrate that the PolE enzyme functions as an Fe2+/pterin-dependent L-isoleucine desaturase. Moreover we illustrate that PolF is a new member of the emerging haem-oxygenase-like diiron oxidases, converting the desaturated L-isoleucine to polyoximic acid via an intramolecular C-N cyclization. Remarkably, we also establish that PolF exhibits dual functionality, orchestrating the sequential desaturation and cyclization with L-isoleucine as the initial substrate. Finally, our combined structural and quantum-mechanics/molecular-mechanics studies show that the PolF enzyme employs an extraordinary mechanism for the construction of the azetidine-containing moiety. These findings expand our knowledge on the catalysis of metalloenzymes and open the way for rational access of more azetidine-related molecules.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 1","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature chemistryPub Date : 2025-09-30DOI: 10.1038/s41557-025-01947-0
Qi Zhang, Valentin P. Nicu, Wybren Jan Buma, He Tian, Da-Hui Qu, Ben L. Feringa
{"title":"Dual dynamic helical poly(disulfide)s with conformational adaptivity and configurational recyclability","authors":"Qi Zhang, Valentin P. Nicu, Wybren Jan Buma, He Tian, Da-Hui Qu, Ben L. Feringa","doi":"10.1038/s41557-025-01947-0","DOIUrl":"10.1038/s41557-025-01947-0","url":null,"abstract":"The structural dynamics of biopolymers, such as proteins and DNA, feature the unique combination of simultaneous conformational adaptivity and configurational reversibility. However, it remains challenging to design a synthetic system featuring dynamic covalent bonds with secondary structural folding and full recycling capabilities. Here we present a synthetic covalent polymer, constructed from biologically relevant units (amino acids and disulfides), that can reversibly adapt between disordered and helical conformations and can recycle itself to the original small molecules. This dual dynamic feature arises from the subtle synergy of noncovalent bonds (H bonds) and dynamic covalent bonds within a coupled chemical equilibrium, of which thermodynamics is found to follow a nonlinear van’t Hoff equation with nonzero heat capacity change. The covalent polymers show conformational dynamics between structured helices and disordered coils and the ability to convert back to the original monomers. This system demonstrates how dual dynamic function can control helical and recyclable polymer formation. Covalent polymers with helical conformations offer an adaptive scaffold for smart materials, but polymer-to-monomer deconstruction is inhibited by the covalent backbone. Now it has been shown that poly(disulfide)s can be folded into helices driven by side-chain hydrogen-bonding self-assembly, resulting in a synthetic helical polymer that can be fully recycled.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 10","pages":"1462-1468"},"PeriodicalIF":20.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}