Conceptual frameworks that describe the electronic structure of molecules are an integral part of understanding chemical structures and reaction mechanisms and designing organic compounds. Here we develop a preliminary set of design guidelines for controlling the electronic structure of DNA. Recent work indicates that charge delocalization occurs over several bases and results in coherence lengths greater than a single base pair. To examine the interactions between bases and their effects on delocalization, this study investigates the influence of nearest-neighbour base pair interactions on the charge transport properties of DNA duplexes that are predominantly composed of guanine-cytosine base pairs. Results show that, by manipulating the sequence, the conductance can be substantially modified without altering the molecular composition. The electronic density of states are then analysed to deduce a set of design guidelines aimed at maintaining high conductance values in long duplexes. Utilizing these rules, we demonstrate that 20-base-pair DNA sequences can exhibit conductance values surpassing 1 × 10-3G0.
{"title":"Developing design guidelines for controlling charge transport in DNA.","authors":"Zahra Aminiranjbar, Caglanaz Akin Gultakti, Amy Zhang, Ersin Emre Oren, Joshua Hihath","doi":"10.1038/s41557-025-01999-2","DOIUrl":"10.1038/s41557-025-01999-2","url":null,"abstract":"<p><p>Conceptual frameworks that describe the electronic structure of molecules are an integral part of understanding chemical structures and reaction mechanisms and designing organic compounds. Here we develop a preliminary set of design guidelines for controlling the electronic structure of DNA. Recent work indicates that charge delocalization occurs over several bases and results in coherence lengths greater than a single base pair. To examine the interactions between bases and their effects on delocalization, this study investigates the influence of nearest-neighbour base pair interactions on the charge transport properties of DNA duplexes that are predominantly composed of guanine-cytosine base pairs. Results show that, by manipulating the sequence, the conductance can be substantially modified without altering the molecular composition. The electronic density of states are then analysed to deduce a set of design guidelines aimed at maintaining high conductance values in long duplexes. Utilizing these rules, we demonstrate that 20-base-pair DNA sequences can exhibit conductance values surpassing 1 × 10<sup>-3</sup>G<sub>0</sub>.</p>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":" ","pages":""},"PeriodicalIF":20.2,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550223","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}
Pub Date : 2025-11-17DOI: 10.1038/s41557-025-02001-9
Chao Wan, Chao Yang, Magnus Rueping, Chen Zhu, Lin Guo, Wujiong Xia
Dearomative functionalization of arenes represents a powerful synthetic strategy for the rapid assembly of complex chemical architectures. A significant challenge in this process is overcoming the inherent aromaticity of arenes. Here, leveraging the potential of organic electrolysis, we show the development of a dearomative syn-1,4-hydroalkylation reaction targeting electron-deficient arenes and heteroarenes. This electrochemical approach, conducted under mild, operationally straightforward and scalable conditions, facilitates the synthesis of alkylated syn-1,4-cyclohexadienes with high chemoselectivity, regioselectivity and stereoselectivity. In addition, this alkylation protocol is controllable and switchable. By employing a niobium plate as the anode and nBu4NBr as the supporting electrolyte, our method enables the para-selective C(sp2)–H alkylation of (hetero)arenes via electrolysis. Both reactions exhibit broad substrate scope and demonstrate excellent compatibility with various electron-deficient arenes and alkyl bromides. Furthermore, preliminary mechanistic studies and density functional theory calculations have been performed to elucidate the reaction mechanism and to rationalize the observed chemoselectivity, regioselectivity and stereoselectivity. Dearomative functionalization is an extraordinary approach for transforming inert, two-dimensional arenes into three-dimensional architectures. Now it has been shown that electrolysis could facilitate dearomative syn-1,4-hydroalkylation and para-selective C(sp2)–H alkylation of electron-deficient (hetero)arenes. Mechanistic studies indicate that the chemoselectivity is primarily governed by the choice of supporting electrolyte and electrode.
{"title":"Dearomative syn-1,4-hydroalkylation and C(sp2)−H alkylation of arenes controlled by chemoselective electrolysis","authors":"Chao Wan, Chao Yang, Magnus Rueping, Chen Zhu, Lin Guo, Wujiong Xia","doi":"10.1038/s41557-025-02001-9","DOIUrl":"10.1038/s41557-025-02001-9","url":null,"abstract":"Dearomative functionalization of arenes represents a powerful synthetic strategy for the rapid assembly of complex chemical architectures. A significant challenge in this process is overcoming the inherent aromaticity of arenes. Here, leveraging the potential of organic electrolysis, we show the development of a dearomative syn-1,4-hydroalkylation reaction targeting electron-deficient arenes and heteroarenes. This electrochemical approach, conducted under mild, operationally straightforward and scalable conditions, facilitates the synthesis of alkylated syn-1,4-cyclohexadienes with high chemoselectivity, regioselectivity and stereoselectivity. In addition, this alkylation protocol is controllable and switchable. By employing a niobium plate as the anode and nBu4NBr as the supporting electrolyte, our method enables the para-selective C(sp2)–H alkylation of (hetero)arenes via electrolysis. Both reactions exhibit broad substrate scope and demonstrate excellent compatibility with various electron-deficient arenes and alkyl bromides. Furthermore, preliminary mechanistic studies and density functional theory calculations have been performed to elucidate the reaction mechanism and to rationalize the observed chemoselectivity, regioselectivity and stereoselectivity. Dearomative functionalization is an extraordinary approach for transforming inert, two-dimensional arenes into three-dimensional architectures. Now it has been shown that electrolysis could facilitate dearomative syn-1,4-hydroalkylation and para-selective C(sp2)–H alkylation of electron-deficient (hetero)arenes. Mechanistic studies indicate that the chemoselectivity is primarily governed by the choice of supporting electrolyte and electrode.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"386-397"},"PeriodicalIF":20.2,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541343","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}
Pub Date : 2025-11-14DOI: 10.1038/s41557-025-01984-9
Abraham Herzog-Arbeitman, Ilia Kevlishvili, Devosmita Sen, Julianna Lian, Joshika Chakraverty, Peter Mueller, Shu Wang, Bradley D. Olsen, Heather J. Kulik, Stephen L. Craig, Jeremiah A. Johnson
Customizing the toughness of polymer networks independently of their chemical composition and topology remains an unsolved challenge. Traditionally, polymer network toughening is achieved by using specialized monomers or solvents or adding secondary networks/fillers that substantially alter the composition and may limit applications. Here we report a class of force-responsive molecules—tetrafunctional cyclobutanes (TCBs)—that enable the synthesis of single-network end-linked gels with substantially decreased or increased toughness, including unusually high toughness for dilute end-linked gels, with no other changes to network composition. This behaviour arises from stress-selective force-coupled TCB reactivity when stress is imparted from multiple directions simultaneously, which traditional bifunctional mechanophores cannot access. This molecular-scale mechanoreactivity translates to bulk toughness through a topological descriptor, network strand continuity, that describes the effect of TCB reactivity on the consequent local network topology. TCB mechanophores and the corresponding concepts of stress-selective force-coupled reactivity and strand continuity offer design principles for tuning the toughness of simple yet commonly used single-network gels. Toughness and stiffness in polymer gels are generally coupled to the network structure and composition. Now it has been shown that stress-selective mechanophore junctions—tetrafunctional cyclobutanes (TCBs)—with minor structural modifications can tune these properties independently in end-linked gels. TCBs increase or decrease toughness by remodelling network topology at the crack tip.
{"title":"Tetrafunctional cyclobutanes tune toughness via network strand continuity","authors":"Abraham Herzog-Arbeitman, Ilia Kevlishvili, Devosmita Sen, Julianna Lian, Joshika Chakraverty, Peter Mueller, Shu Wang, Bradley D. Olsen, Heather J. Kulik, Stephen L. Craig, Jeremiah A. Johnson","doi":"10.1038/s41557-025-01984-9","DOIUrl":"10.1038/s41557-025-01984-9","url":null,"abstract":"Customizing the toughness of polymer networks independently of their chemical composition and topology remains an unsolved challenge. Traditionally, polymer network toughening is achieved by using specialized monomers or solvents or adding secondary networks/fillers that substantially alter the composition and may limit applications. Here we report a class of force-responsive molecules—tetrafunctional cyclobutanes (TCBs)—that enable the synthesis of single-network end-linked gels with substantially decreased or increased toughness, including unusually high toughness for dilute end-linked gels, with no other changes to network composition. This behaviour arises from stress-selective force-coupled TCB reactivity when stress is imparted from multiple directions simultaneously, which traditional bifunctional mechanophores cannot access. This molecular-scale mechanoreactivity translates to bulk toughness through a topological descriptor, network strand continuity, that describes the effect of TCB reactivity on the consequent local network topology. TCB mechanophores and the corresponding concepts of stress-selective force-coupled reactivity and strand continuity offer design principles for tuning the toughness of simple yet commonly used single-network gels. Toughness and stiffness in polymer gels are generally coupled to the network structure and composition. Now it has been shown that stress-selective mechanophore junctions—tetrafunctional cyclobutanes (TCBs)—with minor structural modifications can tune these properties independently in end-linked gels. TCBs increase or decrease toughness by remodelling network topology at the crack tip.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"309-316"},"PeriodicalIF":20.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515689","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}
Pub Date : 2025-11-14DOI: 10.1038/s41557-025-01993-8
Hao Yang, Fusheng Li, Shaoqi Zhan, Yawen Liu, Tianqi Liu, Linqin Wang, Wenlong Li, Mårten S. G. Ahlquist, Sumbal Farid, Rile Ge, Junhu Wang, Marc T. M. Koper, Licheng Sun
Metal (hydro)oxides are among the most effective heterogeneous water oxidation catalysts. Elucidating the interactions between oxygen-bridged metal sites at a molecular level is essential for developing high-performing electrocatalysts. Here we demonstrate that adjacent metal-hydroxyl groups function as intramolecular proton–electron transfer relays to enhance water oxidation kinetics. We achieved this using a well-defined molecular platform with an aza-fused π-conjugated microporous polymer that coordinates molecular Ni or Ni–Fe sites that emulate the structure of the most active edge sites in Ni–Fe materials for studying the heterogeneous water oxidation mechanism. We combine experimental and computational results to reveal the origin of pH-dependent reaction kinetics for O–O bond formation. We find both the anions in solution and the adjacent Ni3+–OH site act as proton transfer relays, facilitating O–O bond formation and leading to pH-dependent water oxidation kinetics. This study provides significant insights into the critical role of electrolyte pH in water oxidation electrocatalysis and enhancement of water oxidation activity in Ni–Fe systems. Intramolecular proton relays are proposed to enhance oxygen evolution for heterogeneous (hydro)oxide electrocatalysts, but molecular-level evidence remains limited. Now it has been shown, using an aza-fused microporous polymer with Ni–Fe sites, that adjacent Ni3+–OH sites relay protons from Fe⁴⁺=O, accelerating the water nucleophilic attack pathway and achieving high turnover frequencies with pH-tunable kinetics.
{"title":"Metal-hydroxyls mediate intramolecular proton transfer in heterogeneous O–O bond formation","authors":"Hao Yang, Fusheng Li, Shaoqi Zhan, Yawen Liu, Tianqi Liu, Linqin Wang, Wenlong Li, Mårten S. G. Ahlquist, Sumbal Farid, Rile Ge, Junhu Wang, Marc T. M. Koper, Licheng Sun","doi":"10.1038/s41557-025-01993-8","DOIUrl":"10.1038/s41557-025-01993-8","url":null,"abstract":"Metal (hydro)oxides are among the most effective heterogeneous water oxidation catalysts. Elucidating the interactions between oxygen-bridged metal sites at a molecular level is essential for developing high-performing electrocatalysts. Here we demonstrate that adjacent metal-hydroxyl groups function as intramolecular proton–electron transfer relays to enhance water oxidation kinetics. We achieved this using a well-defined molecular platform with an aza-fused π-conjugated microporous polymer that coordinates molecular Ni or Ni–Fe sites that emulate the structure of the most active edge sites in Ni–Fe materials for studying the heterogeneous water oxidation mechanism. We combine experimental and computational results to reveal the origin of pH-dependent reaction kinetics for O–O bond formation. We find both the anions in solution and the adjacent Ni3+–OH site act as proton transfer relays, facilitating O–O bond formation and leading to pH-dependent water oxidation kinetics. This study provides significant insights into the critical role of electrolyte pH in water oxidation electrocatalysis and enhancement of water oxidation activity in Ni–Fe systems. Intramolecular proton relays are proposed to enhance oxygen evolution for heterogeneous (hydro)oxide electrocatalysts, but molecular-level evidence remains limited. Now it has been shown, using an aza-fused microporous polymer with Ni–Fe sites, that adjacent Ni3+–OH sites relay protons from Fe⁴⁺=O, accelerating the water nucleophilic attack pathway and achieving high turnover frequencies with pH-tunable kinetics.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"335-344"},"PeriodicalIF":20.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41557-025-01993-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515690","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}
Pub Date : 2025-11-14DOI: 10.1038/s41557-025-01996-5
Arka Porey, Ramon Trevino, Sachchida Nand, Seth O. Fremin, Shree Krishna Dhakal, Babu Raj Dhungana, Arko Das, Vy T. B. Nguyen, William T. Thompson, Dylan P. Moran, Chandan Kumar Giri, Hadi D. Arman, Daniel J. Wherritt, Oleg V. Larionov
Radical pairs generated by light-induced or heat-induced bond cleavage play a central role in biochemical transformations and the synthesis of pharmaceuticals, polymers and industrial chemicals. When such cleavage occurs at a stereocentre in chiral molecules, recombination of the produced radicals can lead to either enantiomer, typically resulting in racemization. Achieving selective conversion of racemic mixtures into single enantiomers is highly desirable yet challenging due to the uncontrolled behaviour of free radicals. Here we show that stereocontrol over these reactions can be achieved through asymmetric geminate recasting: a process in which homolysis and recombination occur within a solvent cage under the influence of a chiral photocatalyst. This strategy enabled the selective construction of chiral sulfur stereocentres via deracemization of sulfinamides, providing access to valuable sulfur-containing building blocks. The approach opens unexplored possibilities for controlling stereochemistry in radical reactions and may inspire broader applications in asymmetric synthesis, medicinal chemistry and materials development. Controlling the stereoselectivity of radical reactions remains a major challenge due to the high reactivity of free radicals. Now it has been shown that asymmetric geminate recasting—a catalytic process in which radicals recombine after bond cleavage—can be used to produce chiral sulfur centres through photocatalytic deracemization of sulfinamides.
{"title":"Construction of sulfur stereocentres by asymmetric geminate recasting","authors":"Arka Porey, Ramon Trevino, Sachchida Nand, Seth O. Fremin, Shree Krishna Dhakal, Babu Raj Dhungana, Arko Das, Vy T. B. Nguyen, William T. Thompson, Dylan P. Moran, Chandan Kumar Giri, Hadi D. Arman, Daniel J. Wherritt, Oleg V. Larionov","doi":"10.1038/s41557-025-01996-5","DOIUrl":"10.1038/s41557-025-01996-5","url":null,"abstract":"Radical pairs generated by light-induced or heat-induced bond cleavage play a central role in biochemical transformations and the synthesis of pharmaceuticals, polymers and industrial chemicals. When such cleavage occurs at a stereocentre in chiral molecules, recombination of the produced radicals can lead to either enantiomer, typically resulting in racemization. Achieving selective conversion of racemic mixtures into single enantiomers is highly desirable yet challenging due to the uncontrolled behaviour of free radicals. Here we show that stereocontrol over these reactions can be achieved through asymmetric geminate recasting: a process in which homolysis and recombination occur within a solvent cage under the influence of a chiral photocatalyst. This strategy enabled the selective construction of chiral sulfur stereocentres via deracemization of sulfinamides, providing access to valuable sulfur-containing building blocks. The approach opens unexplored possibilities for controlling stereochemistry in radical reactions and may inspire broader applications in asymmetric synthesis, medicinal chemistry and materials development. Controlling the stereoselectivity of radical reactions remains a major challenge due to the high reactivity of free radicals. Now it has been shown that asymmetric geminate recasting—a catalytic process in which radicals recombine after bond cleavage—can be used to produce chiral sulfur centres through photocatalytic deracemization of sulfinamides.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1862-1870"},"PeriodicalIF":20.2,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515688","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}
Pub Date : 2025-11-13DOI: 10.1038/s41557-025-01989-4
Sarah May Sibug-Torres, Marika Niihori, Elle Wyatt, Rakesh Arul, Nicolas Spiesshofer, Tabitha Jones, Duncan Graham, Bart de Nijs, Oren A. Scherman, Reshma R. Rao, Mary P. Ryan, Alexander Squires, Christopher N. Savory, David O. Scanlon, Abdalghani Daaoub, Sara Sangtarash, Hatef Sadeghi, Jeremy J. Baumberg
Controlling surface chemistry at the nanoscale is essential for stabilizing structure and tuning function in plasmonic, catalytic and sensing systems, where even trace ligands or ions can reshape surface charge and reactivity. However, probing such dynamic interfaces under operando conditions remains challenging, limiting efforts to engineer nanomaterials with precision. Here, using in situ surface-enhanced Raman spectroscopy, we identify a transient Au–Cl adlayer that forms during electrochemical cycling at gold interfaces. The adlayer exhibits significant charge transfer between gold and chlorine, generating an outward-facing dipole that polarizes neighbouring atoms and modulates the local potential. This dipole stabilizes nanogap interfaces and directs oriented ligand rebinding, enabling reversible reconstruction of subnanometre architectures. It also alters interfacial charge distributions and mediates electron transfer between gold oxidation states, acting as a redox-active intermediate. These findings show how transient surface species shape nanoscale reactivity and stability, offering strategies for designing catalysts, sensors and nanomaterials. Controlling nanoscale interfaces is key for ensuring stable plasmonic and catalytic function yet remains difficult to achieve under operando conditions. Now it has been shown that transient Au–Cl adlayers function as redox-active Au(I) intermediates, modulating interfacial electrostatics. This modulation stabilizes gold nanogaps and directs ligand rebinding, thereby enabling reproducible regeneration of subnanometre architectures.
{"title":"Transient Au–Cl adlayers modulate the surface chemistry of gold nanoparticles during redox reactions","authors":"Sarah May Sibug-Torres, Marika Niihori, Elle Wyatt, Rakesh Arul, Nicolas Spiesshofer, Tabitha Jones, Duncan Graham, Bart de Nijs, Oren A. Scherman, Reshma R. Rao, Mary P. Ryan, Alexander Squires, Christopher N. Savory, David O. Scanlon, Abdalghani Daaoub, Sara Sangtarash, Hatef Sadeghi, Jeremy J. Baumberg","doi":"10.1038/s41557-025-01989-4","DOIUrl":"10.1038/s41557-025-01989-4","url":null,"abstract":"Controlling surface chemistry at the nanoscale is essential for stabilizing structure and tuning function in plasmonic, catalytic and sensing systems, where even trace ligands or ions can reshape surface charge and reactivity. However, probing such dynamic interfaces under operando conditions remains challenging, limiting efforts to engineer nanomaterials with precision. Here, using in situ surface-enhanced Raman spectroscopy, we identify a transient Au–Cl adlayer that forms during electrochemical cycling at gold interfaces. The adlayer exhibits significant charge transfer between gold and chlorine, generating an outward-facing dipole that polarizes neighbouring atoms and modulates the local potential. This dipole stabilizes nanogap interfaces and directs oriented ligand rebinding, enabling reversible reconstruction of subnanometre architectures. It also alters interfacial charge distributions and mediates electron transfer between gold oxidation states, acting as a redox-active intermediate. These findings show how transient surface species shape nanoscale reactivity and stability, offering strategies for designing catalysts, sensors and nanomaterials. Controlling nanoscale interfaces is key for ensuring stable plasmonic and catalytic function yet remains difficult to achieve under operando conditions. Now it has been shown that transient Au–Cl adlayers function as redox-active Au(I) intermediates, modulating interfacial electrostatics. This modulation stabilizes gold nanogaps and directs ligand rebinding, thereby enabling reproducible regeneration of subnanometre architectures.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"294-301"},"PeriodicalIF":20.2,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41557-025-01989-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498843","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}
Pub Date : 2025-11-12DOI: 10.1038/s41557-025-01994-7
Guodong Ju, Xueyuan Yan, Haohao Bai, Mengyuan Liu, Xinping Xi, Yi Liu, Genping Huang, Chao Wang
Stereodivergent construction of multiple stereocentres is one of the most essential tasks in asymmetric synthesis. However, strategies for assembling all possible stereoisomers of optically active compounds bearing non-adjacent stereocentres remain scarce and suffer from certain limitations in terms of reaction types and chemical space. Here we succeed in utilizing the chain walking strategy to realize the simultaneous construction of acyclic 1,n-non-adjacent (n = 3 or 4) stereocentres via Ni-catalysed migratory hydroalkylation of trisubstituted alkenes in an enantioselective and diastereodivergent manner. A series of alkyl units can be site-selectively installed at α-C(sp3)–H sites adjacent to nitrogen, affording chiral amines bearing an α-stereogenic centre and a remote (γ- or δ-) all-alkyl-substituted stereocentre. All four stereoisomers can be accessed using a single catalyst via an appropriate selection of the olefin geometry and ligand configuration, with exceptional control of stereochemistry. This simple and mild platform offers opportunities for the streamlined synthesis of complex bioactive molecules and medicinally relevant scaffolds. Stereodivergent construction of non-adjacent stereocentres remains challenging in asymmetric synthesis, with prior examples limited to one cyclic or allenic stereocentre. Now it has been shown that Ni-catalysed migratory hydroalkylation of trisubstituted alkenes enables enantio- and diastereodivergent access to all four stereoisomers of acyclic molecules bearing remote 1,3- or 1,4-stereocentres.
{"title":"Stereodivergent construction of non-adjacent stereocentres via migratory functionalization of alkenes","authors":"Guodong Ju, Xueyuan Yan, Haohao Bai, Mengyuan Liu, Xinping Xi, Yi Liu, Genping Huang, Chao Wang","doi":"10.1038/s41557-025-01994-7","DOIUrl":"10.1038/s41557-025-01994-7","url":null,"abstract":"Stereodivergent construction of multiple stereocentres is one of the most essential tasks in asymmetric synthesis. However, strategies for assembling all possible stereoisomers of optically active compounds bearing non-adjacent stereocentres remain scarce and suffer from certain limitations in terms of reaction types and chemical space. Here we succeed in utilizing the chain walking strategy to realize the simultaneous construction of acyclic 1,n-non-adjacent (n = 3 or 4) stereocentres via Ni-catalysed migratory hydroalkylation of trisubstituted alkenes in an enantioselective and diastereodivergent manner. A series of alkyl units can be site-selectively installed at α-C(sp3)–H sites adjacent to nitrogen, affording chiral amines bearing an α-stereogenic centre and a remote (γ- or δ-) all-alkyl-substituted stereocentre. All four stereoisomers can be accessed using a single catalyst via an appropriate selection of the olefin geometry and ligand configuration, with exceptional control of stereochemistry. This simple and mild platform offers opportunities for the streamlined synthesis of complex bioactive molecules and medicinally relevant scaffolds. Stereodivergent construction of non-adjacent stereocentres remains challenging in asymmetric synthesis, with prior examples limited to one cyclic or allenic stereocentre. Now it has been shown that Ni-catalysed migratory hydroalkylation of trisubstituted alkenes enables enantio- and diastereodivergent access to all four stereoisomers of acyclic molecules bearing remote 1,3- or 1,4-stereocentres.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"18 2","pages":"345-355"},"PeriodicalIF":20.2,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492556","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}
Pub Date : 2025-11-12DOI: 10.1038/s41557-025-01907-8
Christian A. Choe, Johan O. L. Andreasson, Feriel Melaine, Wipapat Kladwang, Michelle J. Wu, Fernando Portela, Roger Wellington-Oguri, John J. Nicol, Hannah K. Wayment-Steele, Michael Gotrik, Eterna Participants, Purvesh Khatri, William J. Greenleaf, Rhiju Das
Designing single molecules that compute general functions of input molecular partners is a major unsolved challenge in molecular design. Here we demonstrate that high-throughput, iterative experimental testing of diverse RNA designs crowdsourced from the online game Eterna yields sensors of increasingly complex functions of input oligonucleotide concentrations. After designing single-input RNA sensors with activation ratios beyond our detection limits, we created logic gates, including challenging XOR and XNOR gates, and sensors that respond to the ratio of two inputs. Finally, we describe the OpenTB challenge, which elicited 85-nucleotide sensors that compute a score for diagnosing active tuberculosis based on the ratio of products of three gene segments. Building on OpenTB design strategies, we created an algorithm, Nucleologic, that produces similarly compact sensors for the three-gene score based on RNA and DNA. These results expand the possibilities for using compact, single-molecule sensors in a range of applications previously constrained by design complexity. Designing single molecules capable of complex sensing functions is challenging. Now, using crowdsourced RNA designs from the online game Eterna, compact single-molecule sensors have been demonstrated for a variety of tasks, including a complex three-input tuberculosis diagnostic. The development of a Monte Carlo Tree Search algorithm enabled automated design of similarly sophisticated nucleic-acid sensors.
{"title":"Compact RNA sensors for increasingly complex functions of multiple inputs","authors":"Christian A. Choe, Johan O. L. Andreasson, Feriel Melaine, Wipapat Kladwang, Michelle J. Wu, Fernando Portela, Roger Wellington-Oguri, John J. Nicol, Hannah K. Wayment-Steele, Michael Gotrik, Eterna Participants, Purvesh Khatri, William J. Greenleaf, Rhiju Das","doi":"10.1038/s41557-025-01907-8","DOIUrl":"10.1038/s41557-025-01907-8","url":null,"abstract":"Designing single molecules that compute general functions of input molecular partners is a major unsolved challenge in molecular design. Here we demonstrate that high-throughput, iterative experimental testing of diverse RNA designs crowdsourced from the online game Eterna yields sensors of increasingly complex functions of input oligonucleotide concentrations. After designing single-input RNA sensors with activation ratios beyond our detection limits, we created logic gates, including challenging XOR and XNOR gates, and sensors that respond to the ratio of two inputs. Finally, we describe the OpenTB challenge, which elicited 85-nucleotide sensors that compute a score for diagnosing active tuberculosis based on the ratio of products of three gene segments. Building on OpenTB design strategies, we created an algorithm, Nucleologic, that produces similarly compact sensors for the three-gene score based on RNA and DNA. These results expand the possibilities for using compact, single-molecule sensors in a range of applications previously constrained by design complexity. Designing single molecules capable of complex sensing functions is challenging. Now, using crowdsourced RNA designs from the online game Eterna, compact single-molecule sensors have been demonstrated for a variety of tasks, including a complex three-input tuberculosis diagnostic. The development of a Monte Carlo Tree Search algorithm enabled automated design of similarly sophisticated nucleic-acid sensors.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 12","pages":"1839-1852"},"PeriodicalIF":20.2,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41557-025-01907-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505699","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}
Pub Date : 2025-11-11DOI: 10.1038/s41557-025-01990-x
Luca Massaro, Philipp Neigenfind, Andrew Feng, Gannon Kuehn, Flynn C. Attard, Ava DeSanti, Michael R. Collins, Martin Bravo, Raymond K. Twumasi, Doris Chen, Philippe N. Bolduc, Michael Nicastri, Megan A. Emmanuel, Martins S. Oderinde, Maximilian D. Palkowitz, Xiaofan Zheng, Arianne C. Hunter, Kaid C. Harper, Chet C. Tyrol, Pavel K. Mykhailiuk, Yu Kawamata, Phil S. Baran
The pursuit of increasingly complex, three-dimensional molecules is pushing the boundaries of modern organic synthesis, particularly in drug discovery where rigid, saturated scaffolds such as cyclobutanes, azetidines and oxetanes are in high demand. Here we outline a modular, scalable, chemoselective approach to solve this problem using simple α-bromoacids and aryl halides as intuitive starting materials. As demonstrated herein, a sequential series of nickel-electrocatalytic cross-couplings can be enlisted to enable rapid access to such structures, many of which have been nearly impossible to access before without recourse to time-consuming polar bond disconnections that are inherently limiting in terms of accessible chemical space. The scalability of this new reaction sequence is demonstrated, alongside direct applications to known patented structures. A simple user guide is also presented to accelerate adoption of this strategy in medicinal chemistry and related fields. Molecular scaffolds bearing 1,1-diaryl-substituted four-membered rings remain difficult to access using traditional synthesis. Now it has been shown that a modular, nickel-electrocatalytic sequence enables the programmable, scalable and chemoselective synthesis of these high-value motifs, offering broad utility across drug discovery and showcasing strategic applications to patented intermediates.
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Pub Date : 2025-11-06DOI: 10.1038/s41557-025-01986-7
Shao-Jian Zhang, Junnan Hao, Han Wu, Yiyang Hu, Qianru Chen, Bernt Johannessen, Qianyi Ma, Dan Luo, Shi-Zhang Qiao
Aqueous zinc–iodine batteries are attractive for grid-scale energy storage because of their high safety and rate capability. However, conventional hosts for iodine cathodes are often electrochemically inactive and show weak interaction with polyiodides, which not only compromises the battery energy density, but also fails to eliminate shuttle effects. Here we report an electroactive redox coupling strategy to enhance energy density and suppress shuttle effects of zinc–iodine batteries by incorporating ferrocene in cathodes. The ferrocene enables a reversible ferrocene/ferrocenium redox conversion that couples with polyiodides to form insoluble ferrocenium–polyiodide complexes, thereby suppressing shuttle effects. Moreover, this redox elevates the overall discharge capacity of cathodes to 160.5 mAh gcathode−1 and Coulombic efficiency to over 99.5% at 1 C in coin-cell configurations. A 1.2 ampere-hour pouch cell with high-area-capacity cathodes of 8.4 mAh cm−2 sustains 600 stable cycles at 0.5 C with an average Coulombic efficiency of 99.8%. This finding provides a strategy to address both shuttle effects and host-derived energy density loss for battery applications. Aqueous zinc–iodine batteries offer an inexpensive, safe technology for energy storage, but using inactive host materials limits the energy density and polyiodide shuttling reduces cycling lifetimes. Now it has been shown that integrating electroactive ferrocene into cathodes offers additional capacity to enhance energy density and enables shuttle-free operation.
水锌碘电池因其高安全性和高倍率性能而成为电网规模储能的重要组成部分。然而，传统的碘阴极寄主通常具有电化学活性，并且与多碘化物的相互作用较弱，这不仅影响了电池的能量密度，而且无法消除穿梭效应。在这里，我们报道了一种电活性氧化还原偶联策略，通过在阴极中加入二茂铁来提高锌碘电池的能量密度并抑制穿梭效应。二茂铁能够实现可逆的二茂铁/二茂铁氧化还原转化，与多碘化物偶联形成不溶性二茂铁-多碘化物配合物，从而抑制穿梭效应。此外，这种氧化还原将阴极的总放电容量提高到160.5 mAh g阴极−1，在硬币电池结构中，库仑效率在1c下超过99.5%。1.2安培小时的袋状电池具有8.4 mAh cm−2的高面积容量阴极，可在0.5 C下维持600次稳定循环，平均库仑效率为99.8%。这一发现为解决电池应用中的穿梭效应和宿主衍生的能量密度损失提供了一种策略。水锌碘电池提供了一种廉价、安全的储能技术，但使用非活性宿主材料限制了能量密度，多碘化物的穿梭减少了循环寿命。现在已经证明，将电活性二茂铁集成到阴极中可以提供额外的容量，以提高能量密度并实现无梭运行。
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