The aesthetic and practicality of macroscopic fabrics continue to encourage chemists to weave molecules into interlaced patterns with the aim of providing emergent physical and chemical properties when compared with their starting materials. Weaving purely organic molecular threads into flawless two-dimensional patterns remains a formidable challenge, even though its feasibility has been proposed on several occasions. Herein we describe the synthesis of a flawless, purely organic, free-standing two-dimensional woven polymer network driven by dative B-N bonds. Single crystals of this woven polymer network were obtained and its well-defined woven topology was revealed by X-ray diffraction analysis. Free-standing two-dimensional monolayer nanosheets of the woven polymer network were exfoliated from the layered crystals using Scotch Magic Tape. The surface features of the nanosheets were investigated by integrated low-dose and cryogenic electron microscopy imaging techniques. These findings demonstrate the precise construction of purely organic woven polymer networks and highlight the unique opportunities for the application of woven topologies in two-dimensional organic materials.
宏观织物的美观性和实用性不断鼓励化学家将分子编织成交错的图案,目的是提供与其初始材料相比新出现的物理和化学特性。将纯有机分子线编织成完美无瑕的二维图案仍然是一项艰巨的挑战,尽管其可行性已被多次提出。在此,我们介绍了一种由双向 B-N 键驱动的无缺陷、纯有机、独立的二维编织聚合物网络的合成。我们获得了这种编织聚合物网络的单晶体,并通过 X 射线衍射分析揭示了其清晰的编织拓扑结构。使用 Scotch Magic Tape 从层状晶体中剥离出编织聚合物网络的独立二维单层纳米片。通过综合低剂量和低温电子显微镜成像技术研究了纳米片的表面特征。这些研究结果表明了纯有机编织聚合物网络的精确构造,并强调了在二维有机材料中应用编织拓扑结构的独特机遇。
{"title":"Single crystals of purely organic free-standing two-dimensional woven polymer networks.","authors":"Ding Xiao, Zhitong Jin, Guan Sheng, Liya Chen, Xuedong Xiao, Tianyu Shan, Jiao Wang, Rahul Navik, Jianping Xu, Lin Zhou, Qing-Hui Guo, Guangfeng Li, Yihan Zhu, J Fraser Stoddart, Feihe Huang","doi":"10.1038/s41557-024-01580-3","DOIUrl":"https://doi.org/10.1038/s41557-024-01580-3","url":null,"abstract":"<p><p>The aesthetic and practicality of macroscopic fabrics continue to encourage chemists to weave molecules into interlaced patterns with the aim of providing emergent physical and chemical properties when compared with their starting materials. Weaving purely organic molecular threads into flawless two-dimensional patterns remains a formidable challenge, even though its feasibility has been proposed on several occasions. Herein we describe the synthesis of a flawless, purely organic, free-standing two-dimensional woven polymer network driven by dative B-N bonds. Single crystals of this woven polymer network were obtained and its well-defined woven topology was revealed by X-ray diffraction analysis. Free-standing two-dimensional monolayer nanosheets of the woven polymer network were exfoliated from the layered crystals using Scotch Magic Tape. The surface features of the nanosheets were investigated by integrated low-dose and cryogenic electron microscopy imaging techniques. These findings demonstrate the precise construction of purely organic woven polymer networks and highlight the unique opportunities for the application of woven topologies in two-dimensional organic materials.</p>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724010","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 : 2024-07-16DOI: 10.1038/s41557-024-01570-5
Christine M. E. Kriebisch, Ludwig Burger, Oleksii Zozulia, Michele Stasi, Alexander Floroni, Dieter Braun, Ulrich Gerland, Job Boekhoven
One of science’s greatest challenges is determining how life can spontaneously emerge from a mixture of molecules. A complicating factor is that life and its molecules are inherently unstable—RNA and proteins are prone to hydrolysis and denaturation. For the de novo synthesis of life or to better understand its emergence at its origin, selection mechanisms are needed for unstable molecules. Here we present a chemically fuelled dynamic combinatorial library to model RNA oligomerization and deoligomerization and shine new light on selection and purification mechanisms under kinetic control. In the experiments, oligomers can only be sustained by continuous production. Hybridization is a powerful tool for selecting unstable molecules, offering feedback on oligomerization and deoligomerization rates. Moreover, we find that templation can be used to purify libraries of oligomers. In addition, template-assisted formation of oligomers within coacervate-based protocells changes its compartment’s physical properties, such as their ability to fuse. Such reciprocal coupling between oligomer production and physical properties is a key step towards synthetic life. Selection mechanisms were critical at the emergence of life and will also be important for the synthesis of life. Now, it has been shown that template-based copying controls the selection of unstable molecules in a chemically fuelled dynamic combinatorial library. Moreover, when encapsulated inside coacervate droplets, these mechanisms change the coacervate’s physical properties.
{"title":"Template-based copying in chemically fuelled dynamic combinatorial libraries","authors":"Christine M. E. Kriebisch, Ludwig Burger, Oleksii Zozulia, Michele Stasi, Alexander Floroni, Dieter Braun, Ulrich Gerland, Job Boekhoven","doi":"10.1038/s41557-024-01570-5","DOIUrl":"10.1038/s41557-024-01570-5","url":null,"abstract":"One of science’s greatest challenges is determining how life can spontaneously emerge from a mixture of molecules. A complicating factor is that life and its molecules are inherently unstable—RNA and proteins are prone to hydrolysis and denaturation. For the de novo synthesis of life or to better understand its emergence at its origin, selection mechanisms are needed for unstable molecules. Here we present a chemically fuelled dynamic combinatorial library to model RNA oligomerization and deoligomerization and shine new light on selection and purification mechanisms under kinetic control. In the experiments, oligomers can only be sustained by continuous production. Hybridization is a powerful tool for selecting unstable molecules, offering feedback on oligomerization and deoligomerization rates. Moreover, we find that templation can be used to purify libraries of oligomers. In addition, template-assisted formation of oligomers within coacervate-based protocells changes its compartment’s physical properties, such as their ability to fuse. Such reciprocal coupling between oligomer production and physical properties is a key step towards synthetic life. Selection mechanisms were critical at the emergence of life and will also be important for the synthesis of life. Now, it has been shown that template-based copying controls the selection of unstable molecules in a chemically fuelled dynamic combinatorial library. Moreover, when encapsulated inside coacervate droplets, these mechanisms change the coacervate’s physical properties.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41557-024-01570-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141624693","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 : 2024-07-15DOI: 10.1038/s41557-024-01573-2
Carson C. Cole, Douglas R. Walker, Sarah A. H. Hulgan, Brett H. Pogostin, Joseph W. R. Swain, Mitchell D. Miller, Weijun Xu, Ryan Duella, Mikita Misiura, Xu Wang, Anatoly B. Kolomeisky, George N. Philips, Jeffrey D. Hartgerink
The most abundant natural collagens form heterotrimeric triple helices. Synthetic mimics of collagen heterotrimers have been found to fold slowly, even compared to the already slow rates of homotrimeric helices. These prolonged folding rates are not understood. Here we compare the stabilities, specificities and folding rates of three heterotrimeric collagen mimics designed through a computationally assisted approach. The crystal structure of one ABC-type heterotrimer verified a well-controlled composition and register and elucidated the geometry of pairwise cation–π and axial and lateral salt bridges in the assembly. This collagen heterotrimer folds much faster (hours versus days) than comparable, well-designed systems. Circular dichroism and NMR data suggest the folding is frustrated by unproductive, competing heterotrimer species and these species must unwind before refolding into the thermodynamically favoured assembly. The heterotrimeric collagen folding rate is inhibited by the introduction of preformed competing triple-helical assemblies, which suggests that slow heterotrimer folding kinetics are dominated by the frustration of the energy landscape caused by competing triple helices.
{"title":"Heterotrimeric collagen helix with high specificity of assembly results in a rapid rate of folding","authors":"Carson C. Cole, Douglas R. Walker, Sarah A. H. Hulgan, Brett H. Pogostin, Joseph W. R. Swain, Mitchell D. Miller, Weijun Xu, Ryan Duella, Mikita Misiura, Xu Wang, Anatoly B. Kolomeisky, George N. Philips, Jeffrey D. Hartgerink","doi":"10.1038/s41557-024-01573-2","DOIUrl":"https://doi.org/10.1038/s41557-024-01573-2","url":null,"abstract":"<p>The most abundant natural collagens form heterotrimeric triple helices. Synthetic mimics of collagen heterotrimers have been found to fold slowly, even compared to the already slow rates of homotrimeric helices. These prolonged folding rates are not understood. Here we compare the stabilities, specificities and folding rates of three heterotrimeric collagen mimics designed through a computationally assisted approach. The crystal structure of one ABC-type heterotrimer verified a well-controlled composition and register and elucidated the geometry of pairwise cation–<i>π</i> and axial and lateral salt bridges in the assembly. This collagen heterotrimer folds much faster (hours versus days) than comparable, well-designed systems. Circular dichroism and NMR data suggest the folding is frustrated by unproductive, competing heterotrimer species and these species must unwind before refolding into the thermodynamically favoured assembly. The heterotrimeric collagen folding rate is inhibited by the introduction of preformed competing triple-helical assemblies, which suggests that slow heterotrimer folding kinetics are dominated by the frustration of the energy landscape caused by competing triple helices.</p><figure></figure>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618383","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 : 2024-07-15DOI: 10.1038/s41557-024-01586-x
Chenyang Hu, Nicolas H. Rees, Maren Pink, Jose M. Goicoechea
Nitroso compounds, R–N=O, are common intermediates in organic synthesis, and are typically amenable to storage and manipulation at ambient temperature under aerobic conditions. By contrast, phosphorus-containing analogues, such as R–P=O (R = OH, CH3, OCH3, Ph), are extremely reactive and need to be studied in inert gas matrices at ultralow temperatures (3–15 K). These species are believed to be key intermediates in the degradation/combustion of organic phosphorus compounds, a class of chemicals that includes chemical warfare agents and flame retardants. Here we describe the isolation of a two-coordinate phosphorus(III) oxide under ambient conditions, enabled by the use of an extremely bulky amine ligand. Reactivity studies reveal that the phosphorus centre can be readily oxidized, and that in doing so, the P–O bond remains intact, an observation that is of interest to the proposed reactivity of transient phosphorus(III) oxides.
{"title":"Isolation and characterization of a two-coordinate phosphinidene oxide","authors":"Chenyang Hu, Nicolas H. Rees, Maren Pink, Jose M. Goicoechea","doi":"10.1038/s41557-024-01586-x","DOIUrl":"https://doi.org/10.1038/s41557-024-01586-x","url":null,"abstract":"<p>Nitroso compounds, R–N=O, are common intermediates in organic synthesis, and are typically amenable to storage and manipulation at ambient temperature under aerobic conditions. By contrast, phosphorus-containing analogues, such as R–P=O (R = OH, CH<sub>3</sub>, OCH<sub>3</sub>, Ph), are extremely reactive and need to be studied in inert gas matrices at ultralow temperatures (3–15 K). These species are believed to be key intermediates in the degradation/combustion of organic phosphorus compounds, a class of chemicals that includes chemical warfare agents and flame retardants. Here we describe the isolation of a two-coordinate phosphorus(III) oxide under ambient conditions, enabled by the use of an extremely bulky amine ligand. Reactivity studies reveal that the phosphorus centre can be readily oxidized, and that in doing so, the P–O bond remains intact, an observation that is of interest to the proposed reactivity of transient phosphorus(III) oxides.</p><figure></figure>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618385","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 : 2024-07-15DOI: 10.1038/s41557-024-01584-z
Colin P. Pilkington, Ignacio Gispert, Suet Y. Chui, John. M. Seddon, Yuval Elani
Soft-matter nanoscale assemblies such as liposomes and lipid nanoparticles have the potential to deliver and release multiple cargos in an externally stimulated and site-specific manner. Such assemblies are currently structurally simplistic, comprising spherical capsules or lipid clusters. Given that form and function are intertwined, this lack of architectural complexity restricts the development of more sophisticated properties. To address this, we have devised an engineering strategy combining microfluidics and conjugation chemistry to synthesize nanosized liposomes with two discrete compartments, one within another, which we term concentrisomes. We can control the composition of each bilayer and tune both particle size and the dimensions between inner and outer membranes. We can specify the identity of encapsulated cargo within each compartment, and the biophysical features of inner and outer bilayers, allowing us to imbue each bilayer with different stimuli-responsive properties. We use these particles for multi-stage release of two payloads at defined time points, and as attolitre reactors for triggered in situ biochemical synthesis.
{"title":"Engineering a nanoscale liposome-in-liposome for in situ biochemical synthesis and multi-stage release","authors":"Colin P. Pilkington, Ignacio Gispert, Suet Y. Chui, John. M. Seddon, Yuval Elani","doi":"10.1038/s41557-024-01584-z","DOIUrl":"https://doi.org/10.1038/s41557-024-01584-z","url":null,"abstract":"<p>Soft-matter nanoscale assemblies such as liposomes and lipid nanoparticles have the potential to deliver and release multiple cargos in an externally stimulated and site-specific manner. Such assemblies are currently structurally simplistic, comprising spherical capsules or lipid clusters. Given that form and function are intertwined, this lack of architectural complexity restricts the development of more sophisticated properties. To address this, we have devised an engineering strategy combining microfluidics and conjugation chemistry to synthesize nanosized liposomes with two discrete compartments, one within another, which we term concentrisomes. We can control the composition of each bilayer and tune both particle size and the dimensions between inner and outer membranes. We can specify the identity of encapsulated cargo within each compartment, and the biophysical features of inner and outer bilayers, allowing us to imbue each bilayer with different stimuli-responsive properties. We use these particles for multi-stage release of two payloads at defined time points, and as attolitre reactors for triggered in situ biochemical synthesis.</p><figure></figure>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618384","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 : 2024-07-15DOI: 10.1038/s41557-024-01585-y
Baochen Ma, Haikuo Zhang, Ruhong Li, Shuoqing Zhang, Long Chen, Tao Zhou, Jinze Wang, Ruixin Zhang, Shouhong Ding, Xuezhang Xiao, Tao Deng, Lixin Chen, Xiulin Fan
Ideal rechargeable lithium battery electrolytes should promote the Faradaic reaction near the electrode surface while mitigating undesired side reactions. Yet, conventional electrolytes usually show sluggish kinetics and severe degradation due to their high desolvation energy and poor compatibility. Here we propose an electrolyte design strategy that overcomes the limitations associated with Li salt dissociation in non-coordinating solvents to enable fast, stable Li chemistries. The non-coordinating solvents are activated through favourable hydrogen bond interactions, specifically Fδ−–Hδ+ or Hδ+–Oδ−, when blended with fluorinated benzenes or halide alkane compounds. These intermolecular interactions enable a dynamic Li+–solvent coordination process, thereby promoting the fast Li+ reaction kinetics and suppressing electrode side reactions. Utilizing this molecular-docking electrolyte design strategy, we have developed 25 electrolytes that demonstrate high Li plating/stripping Coulombic efficiencies and promising capacity retentions in both full cells and pouch cells. This work supports the use of the molecular-docking solvation mechanism for designing electrolytes with fast Li+ kinetics for high-voltage Li batteries. Conventional Li-ion battery electrolytes often show sluggish kinetics and severe degradation due to high Li+ desolvation energies and poor compatibility. Now, a molecular-docking strategy between solvents and inducers has been shown to enable dynamic Li+ coordination that promotes fast, stable and high-voltage lithium battery chemistries.
{"title":"Molecular-docking electrolytes enable high-voltage lithium battery chemistries","authors":"Baochen Ma, Haikuo Zhang, Ruhong Li, Shuoqing Zhang, Long Chen, Tao Zhou, Jinze Wang, Ruixin Zhang, Shouhong Ding, Xuezhang Xiao, Tao Deng, Lixin Chen, Xiulin Fan","doi":"10.1038/s41557-024-01585-y","DOIUrl":"10.1038/s41557-024-01585-y","url":null,"abstract":"Ideal rechargeable lithium battery electrolytes should promote the Faradaic reaction near the electrode surface while mitigating undesired side reactions. Yet, conventional electrolytes usually show sluggish kinetics and severe degradation due to their high desolvation energy and poor compatibility. Here we propose an electrolyte design strategy that overcomes the limitations associated with Li salt dissociation in non-coordinating solvents to enable fast, stable Li chemistries. The non-coordinating solvents are activated through favourable hydrogen bond interactions, specifically Fδ−–Hδ+ or Hδ+–Oδ−, when blended with fluorinated benzenes or halide alkane compounds. These intermolecular interactions enable a dynamic Li+–solvent coordination process, thereby promoting the fast Li+ reaction kinetics and suppressing electrode side reactions. Utilizing this molecular-docking electrolyte design strategy, we have developed 25 electrolytes that demonstrate high Li plating/stripping Coulombic efficiencies and promising capacity retentions in both full cells and pouch cells. This work supports the use of the molecular-docking solvation mechanism for designing electrolytes with fast Li+ kinetics for high-voltage Li batteries. Conventional Li-ion battery electrolytes often show sluggish kinetics and severe degradation due to high Li+ desolvation energies and poor compatibility. Now, a molecular-docking strategy between solvents and inducers has been shown to enable dynamic Li+ coordination that promotes fast, stable and high-voltage lithium battery chemistries.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618382","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 : 2024-07-09DOI: 10.1038/s41557-024-01557-2
Xuexiang Han, Mohamad-Gabriel Alameh, Ningqiang Gong, Lulu Xue, Majed Ghattas, Goutham Bojja, Junchao Xu, Gan Zhao, Claude C. Warzecha, Marshall S. Padilla, Rakan El-Mayta, Garima Dwivedi, Ying Xu, Andrew E. Vaughan, James M. Wilson, Drew Weissman, Michael J. Mitchell
Lipid nanoparticles (LNPs) are widely used for mRNA delivery, with cationic lipids greatly affecting biodistribution, cellular uptake, endosomal escape and transfection efficiency. However, the laborious synthesis of cationic lipids limits the discovery of efficacious candidates and slows down scale-up manufacturing. Here we develop a one-pot, tandem multi-component reaction based on the rationally designed amine–thiol–acrylate conjugation, which enables fast (1 h) and facile room-temperature synthesis of amidine-incorporated degradable (AID) lipids. Structure–activity relationship analysis of a combinatorial library of 100 chemically diverse AID-lipids leads to the identification of a tail-like amine–ring-alkyl aniline that generally affords efficacious lipids. Experimental and theoretical studies show that the embedded bulky benzene ring can enhance endosomal escape and mRNA delivery by enabling the lipid to adopt a more conical shape. The lead AID-lipid can not only mediate local delivery of mRNA vaccines and systemic delivery of mRNA therapeutics, but can also alter the tropism of liver-tropic LNPs to selectively deliver gene editors to the lung and mRNA vaccines to the spleen.
脂质纳米颗粒(LNPs)被广泛用于 mRNA 递送,其中阳离子脂质对生物分布、细胞摄取、内体逸出和转染效率有很大影响。然而,阳离子脂质的合成十分费力,这限制了高效候选物的发现,也减缓了规模化生产的速度。在此,我们开发了一种基于合理设计的胺-硫醇-丙烯酸酯共轭的单锅串联多组分反应,它能快速(1 小时)、简便地室温合成胺并入可降解(AID)脂质。通过对由 100 种化学性质不同的 AID 脂类组成的组合库进行结构-活性关系分析,确定了一种尾部类似胺-环-烷基苯胺的脂类,这种脂类一般都能产生有效的脂类。实验和理论研究表明,嵌入的笨重苯环能使脂质采用更圆锥的形状,从而增强内体逸出和 mRNA 递送。先导 AID 脂质不仅可以介导 mRNA 疫苗的局部递送和 mRNA 治疗药物的全身递送,而且还可以改变肝毒性 LNPs 的趋向性,从而有选择地将基因编辑器递送到肺部,将 mRNA 疫苗递送到脾脏。
{"title":"Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo","authors":"Xuexiang Han, Mohamad-Gabriel Alameh, Ningqiang Gong, Lulu Xue, Majed Ghattas, Goutham Bojja, Junchao Xu, Gan Zhao, Claude C. Warzecha, Marshall S. Padilla, Rakan El-Mayta, Garima Dwivedi, Ying Xu, Andrew E. Vaughan, James M. Wilson, Drew Weissman, Michael J. Mitchell","doi":"10.1038/s41557-024-01557-2","DOIUrl":"https://doi.org/10.1038/s41557-024-01557-2","url":null,"abstract":"<p>Lipid nanoparticles (LNPs) are widely used for mRNA delivery, with cationic lipids greatly affecting biodistribution, cellular uptake, endosomal escape and transfection efficiency. However, the laborious synthesis of cationic lipids limits the discovery of efficacious candidates and slows down scale-up manufacturing. Here we develop a one-pot, tandem multi-component reaction based on the rationally designed amine–thiol–acrylate conjugation, which enables fast (1 h) and facile room-temperature synthesis of amidine-incorporated degradable (AID) lipids. Structure–activity relationship analysis of a combinatorial library of 100 chemically diverse AID-lipids leads to the identification of a tail-like amine–ring-alkyl aniline that generally affords efficacious lipids. Experimental and theoretical studies show that the embedded bulky benzene ring can enhance endosomal escape and mRNA delivery by enabling the lipid to adopt a more conical shape. The lead AID-lipid can not only mediate local delivery of mRNA vaccines and systemic delivery of mRNA therapeutics, but can also alter the tropism of liver-tropic LNPs to selectively deliver gene editors to the lung and mRNA vaccines to the spleen.</p><figure></figure>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561599","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 : 2024-07-08DOI: 10.1038/s41557-024-01575-0
Stacey-Lynn Paiva
Tanja Mittag talks to Nature Chemistry about how her path in research led to her work in phase separation and her thoughts about the future of the field.
{"title":"Phase by phase through a condensate researcher''s career path","authors":"Stacey-Lynn Paiva","doi":"10.1038/s41557-024-01575-0","DOIUrl":"10.1038/s41557-024-01575-0","url":null,"abstract":"Tanja Mittag talks to Nature Chemistry about how her path in research led to her work in phase separation and her thoughts about the future of the field.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559192","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 : 2024-07-08DOI: 10.1038/s41557-024-01559-0
Adam Weingarten
The electrochemical double layer dictates how many energy conversion and storage technologies operate, but such interfacial systems are challenging to examine. Now, Schreier and colleagues have developed a way to correlate variations in the electrochemical double layer with audible frequency changes to afford real-time ‘audiolization’ of molecular movements.
{"title":"Comparing notes","authors":"Adam Weingarten","doi":"10.1038/s41557-024-01559-0","DOIUrl":"10.1038/s41557-024-01559-0","url":null,"abstract":"The electrochemical double layer dictates how many energy conversion and storage technologies operate, but such interfacial systems are challenging to examine. Now, Schreier and colleagues have developed a way to correlate variations in the electrochemical double layer with audible frequency changes to afford real-time ‘audiolization’ of molecular movements.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559190","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 : 2024-07-08DOI: 10.1038/s41557-024-01587-w
In this issue we feature several articles that explore advances in the study of phase separation. They highlight some recently reported mechanistic features and progress in the methodology used to study it within cells, and they delve into the implications that phase separation has for select cellular functions.
{"title":"The many phases of biomolecular condensates","authors":"","doi":"10.1038/s41557-024-01587-w","DOIUrl":"10.1038/s41557-024-01587-w","url":null,"abstract":"In this issue we feature several articles that explore advances in the study of phase separation. They highlight some recently reported mechanistic features and progress in the methodology used to study it within cells, and they delve into the implications that phase separation has for select cellular functions.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41557-024-01587-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559193","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}