Pub Date : 2024-09-27DOI: 10.1038/s41570-024-00648-5
Daniel Whitaker, Matthew W. Powner
Water is essential for life as we know it, but it has paradoxically been considered inimical to the emergence of life. Proteins and nucleic acids have sustained evolution and life for billions of years, but both are condensation polymers, suggesting that their formation requires the elimination of water. This presents intrinsic challenges at the origins of life, including how condensation polymer synthesis can overcome the thermodynamic pressure of hydrolysis in water and how nucleophiles can kinetically outcompete water to yield condensation products. The answers to these questions lie in balancing thermodynamic activation and kinetic stability. For peptides, an effective strategy is to directly harness the energy trapped in prebiotic molecules, such as nitriles, and avoid the formation of fully hydrolysed monomers. In this Review, we discuss how chemical energy can be built into precursors, retained, and released selectively for polymer synthesis. Looking to the future, the outstanding goals include how nucleic acids can be synthesized, avoiding the formation of fully hydrolysed monomers and what caused information to flow from nucleic acids to proteins. Water is essential for life but paradoxically considered detrimental to the origins of life. Here, we discuss whether avoiding hydrolysed monomers and exploiting the chemical energy in prebiotic precursors may hold the missing key to unlocking biopolymer synthesis.
{"title":"On the aqueous origins of the condensation polymers of life","authors":"Daniel Whitaker, Matthew W. Powner","doi":"10.1038/s41570-024-00648-5","DOIUrl":"10.1038/s41570-024-00648-5","url":null,"abstract":"Water is essential for life as we know it, but it has paradoxically been considered inimical to the emergence of life. Proteins and nucleic acids have sustained evolution and life for billions of years, but both are condensation polymers, suggesting that their formation requires the elimination of water. This presents intrinsic challenges at the origins of life, including how condensation polymer synthesis can overcome the thermodynamic pressure of hydrolysis in water and how nucleophiles can kinetically outcompete water to yield condensation products. The answers to these questions lie in balancing thermodynamic activation and kinetic stability. For peptides, an effective strategy is to directly harness the energy trapped in prebiotic molecules, such as nitriles, and avoid the formation of fully hydrolysed monomers. In this Review, we discuss how chemical energy can be built into precursors, retained, and released selectively for polymer synthesis. Looking to the future, the outstanding goals include how nucleic acids can be synthesized, avoiding the formation of fully hydrolysed monomers and what caused information to flow from nucleic acids to proteins. Water is essential for life but paradoxically considered detrimental to the origins of life. Here, we discuss whether avoiding hydrolysed monomers and exploiting the chemical energy in prebiotic precursors may hold the missing key to unlocking biopolymer synthesis.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 11","pages":"817-832"},"PeriodicalIF":38.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350283","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 : 2024-09-26DOI: 10.1038/s41570-024-00650-x
Kane A. C. Bastick, Dean D. Roberts, Allan J. B. Watson
Organoboron chemistry has become a cornerstone of modern synthetic methodology. Most of these reactions use an organoboron starting material that contains just one C(sp2)–B or C(sp3)–B bond; however, there has been a recent and accelerating trend to prepare multiborylated alkanes that possess two or more C(sp3)–B bonds. This is despite a lack of general reactivity, meaning many of these compounds currently offer limited downstream synthetic value. This Review summarizes recent advances in the exploration of multiborylated alkanes, including a discussion on how these products may be elaborated in further synthetic manipulations. Monoborylated alkanes display diverse reactivity and broad application; however, despite an increasing number of approaches to access them, multiborylated alkanes have yet to realize their synthetic potential. This Review highlights the current state-of-the-art in approaches to and synthetic applications of multiborylated alkanes.
{"title":"The current utility and future potential of multiborylated alkanes","authors":"Kane A. C. Bastick, Dean D. Roberts, Allan J. B. Watson","doi":"10.1038/s41570-024-00650-x","DOIUrl":"10.1038/s41570-024-00650-x","url":null,"abstract":"Organoboron chemistry has become a cornerstone of modern synthetic methodology. Most of these reactions use an organoboron starting material that contains just one C(sp2)–B or C(sp3)–B bond; however, there has been a recent and accelerating trend to prepare multiborylated alkanes that possess two or more C(sp3)–B bonds. This is despite a lack of general reactivity, meaning many of these compounds currently offer limited downstream synthetic value. This Review summarizes recent advances in the exploration of multiborylated alkanes, including a discussion on how these products may be elaborated in further synthetic manipulations. Monoborylated alkanes display diverse reactivity and broad application; however, despite an increasing number of approaches to access them, multiborylated alkanes have yet to realize their synthetic potential. This Review highlights the current state-of-the-art in approaches to and synthetic applications of multiborylated alkanes.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"741-761"},"PeriodicalIF":38.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321275","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 : 2024-09-24DOI: 10.1038/s41570-024-00655-6
Sammer Marzouk, Dang Nguyen, Cameron Sabet
Inhibiting a signal transducer, which kicks off the production of β-lactamase in response to the presence of an antibiotic, shuts down resistance and makes β-lactam antibiotics effective once more.
{"title":"Reviving antibiotic power","authors":"Sammer Marzouk, Dang Nguyen, Cameron Sabet","doi":"10.1038/s41570-024-00655-6","DOIUrl":"10.1038/s41570-024-00655-6","url":null,"abstract":"Inhibiting a signal transducer, which kicks off the production of β-lactamase in response to the presence of an antibiotic, shuts down resistance and makes β-lactam antibiotics effective once more.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"722-722"},"PeriodicalIF":38.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313985","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 : 2024-09-24DOI: 10.1038/s41570-024-00644-9
Alison J. Frontier
2024 marks twenty years of the educational website Not Voodoo: Demystifying Synthetic Organic Chemistry — a fount of knowledge for organic chemistry laboratory techniques, with tips and tricks for both beginning research students and advanced experimentalists.
{"title":"The Not Voodoo website after twenty dynamic years","authors":"Alison J. Frontier","doi":"10.1038/s41570-024-00644-9","DOIUrl":"10.1038/s41570-024-00644-9","url":null,"abstract":"2024 marks twenty years of the educational website Not Voodoo: Demystifying Synthetic Organic Chemistry — a fount of knowledge for organic chemistry laboratory techniques, with tips and tricks for both beginning research students and advanced experimentalists. ","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"713-714"},"PeriodicalIF":38.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308158","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 : 2024-09-23DOI: 10.1038/s41570-024-00654-7
Sihan Xiong, Khalid Shah, Chuang Liu
An mRNA sequence that encodes a zwitterionic polypeptide fused to a therapeutic protein improves the pharmacokinetic properties of mRNA therapeutics.
编码与治疗蛋白融合的齐聚物多肽的 mRNA 序列可改善 mRNA 疗法的药代动力学特性。
{"title":"A zwitterionic twist","authors":"Sihan Xiong, Khalid Shah, Chuang Liu","doi":"10.1038/s41570-024-00654-7","DOIUrl":"10.1038/s41570-024-00654-7","url":null,"abstract":"An mRNA sequence that encodes a zwitterionic polypeptide fused to a therapeutic protein improves the pharmacokinetic properties of mRNA therapeutics.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"721-721"},"PeriodicalIF":38.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276706","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 : 2024-09-20DOI: 10.1038/s41570-024-00653-8
Glenn A. Hurst
Strong partnerships with students are critical to curriculum development and research. This can foster a culture of continual improvement with educational and societal benefit.
{"title":"Student partnerships for sustainable change","authors":"Glenn A. Hurst","doi":"10.1038/s41570-024-00653-8","DOIUrl":"10.1038/s41570-024-00653-8","url":null,"abstract":"Strong partnerships with students are critical to curriculum development and research. This can foster a culture of continual improvement with educational and societal benefit.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"717-718"},"PeriodicalIF":38.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276791","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 : 2024-09-09DOI: 10.1038/s41570-024-00647-6
Arismel Tena Meza, Laura G. Wonilowicz, Neil K. Garg
Chem Kids is a science camp where children ages 10 to 12 years old learn the notoriously difficult subject of organic chemistry.
Chem Kids 是一个科学夏令营，让 10 至 12 岁的儿童学习众所周知的有机化学难点。
{"title":"Organic chemistry for kids","authors":"Arismel Tena Meza, Laura G. Wonilowicz, Neil K. Garg","doi":"10.1038/s41570-024-00647-6","DOIUrl":"10.1038/s41570-024-00647-6","url":null,"abstract":"Chem Kids is a science camp where children ages 10 to 12 years old learn the notoriously difficult subject of organic chemistry.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"715-716"},"PeriodicalIF":38.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160381","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 : 2024-09-09DOI: 10.1038/s41570-024-00645-8
Brandon A. Wright, Richmond Sarpong
The generation of molecular complexity is a primary goal in the field of synthetic chemistry. In the context of retrosynthetic analysis, the concept of molecular complexity is central to identifying productive disconnections and the development of efficient total syntheses. However, this field-defining concept is frequently invoked on an intuitive basis without precise definition or appreciation of its subtleties. Methods for quantifying molecular complexity could prove useful for characterizing the state of synthesis in a more rigorous, reliable and reproducible fashion. As a first step to evaluating the importance of these methods to the state of the field, here we present our perspective on the development of molecular complexity quantification and its implications for chemical synthesis. The extension and application of these methods beyond computer-aided synthesis planning and medicinal chemistry to the traditional practice of ‘complex molecule’ synthesis could have the potential to unearth new opportunities and more efficient approaches for synthesis. Quantifying molecular complexity has the potential to enhance retrosynthetic analysis and, thus, aid the development of efficient total syntheses. This Perspective discusses methods for rigorous, reproducible complexity measurement, highlighting their potential to revolutionize traditional complex molecule synthesis and uncover new synthetic opportunities.
{"title":"Molecular complexity as a driving force for the advancement of organic synthesis","authors":"Brandon A. Wright, Richmond Sarpong","doi":"10.1038/s41570-024-00645-8","DOIUrl":"10.1038/s41570-024-00645-8","url":null,"abstract":"The generation of molecular complexity is a primary goal in the field of synthetic chemistry. In the context of retrosynthetic analysis, the concept of molecular complexity is central to identifying productive disconnections and the development of efficient total syntheses. However, this field-defining concept is frequently invoked on an intuitive basis without precise definition or appreciation of its subtleties. Methods for quantifying molecular complexity could prove useful for characterizing the state of synthesis in a more rigorous, reliable and reproducible fashion. As a first step to evaluating the importance of these methods to the state of the field, here we present our perspective on the development of molecular complexity quantification and its implications for chemical synthesis. The extension and application of these methods beyond computer-aided synthesis planning and medicinal chemistry to the traditional practice of ‘complex molecule’ synthesis could have the potential to unearth new opportunities and more efficient approaches for synthesis. Quantifying molecular complexity has the potential to enhance retrosynthetic analysis and, thus, aid the development of efficient total syntheses. This Perspective discusses methods for rigorous, reproducible complexity measurement, highlighting their potential to revolutionize traditional complex molecule synthesis and uncover new synthetic opportunities.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"776-792"},"PeriodicalIF":38.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160386","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 : 2024-09-02DOI: 10.1038/s41570-024-00646-7
Saman Fatima, Lisa Olshansky
From the reduction of dinitrogen to the oxidation of water, the chemical transformations catalysed by metalloenzymes underlie global geochemical and biochemical cycles. These reactions represent some of the most kinetically and thermodynamically challenging processes known and require the complex choreography of the fundamental building blocks of nature, electrons and protons, to be carried out with utmost precision and accuracy. The rate-determining step of catalysis in many metalloenzymes consists of a protein structural rearrangement, suggesting that nature has evolved to leverage macroscopic changes in protein molecular structure to control subatomic changes in metallocofactor electronic structure. The proton-coupled electron transfer mechanisms operative in nitrogenase, photosystem II and ribonucleotide reductase exemplify this interplay between molecular and electronic structural control. We present the culmination of decades of study on each of these systems and clarify what is known regarding the interplay between structural changes and functional outcomes in these metalloenzyme linchpins. Rate-limiting conformational changes often gate the formation of catalytically active metalloenzyme states. We review examples of the interplay between macroscopic changes in protein molecular structure and subatomic changes in metallocofactor electronic structure that together enable precision control over nature’s redox machines.
从二氮的还原到水的氧化，金属酶催化的化学变化是全球地球化学和生物化学循环的基础。这些反应是已知的动力学和热力学上最具挑战性的过程，需要对自然界的基本组成单元--电子和质子--进行复杂的编排，以达到最高的精确度和准确性。许多金属酶催化作用的决定速率步骤包括蛋白质结构的重新排列，这表明大自然已经进化到可以利用蛋白质分子结构的宏观变化来控制金属因子电子结构的亚原子变化。氮化酶、光系统 II 和核糖核苷酸还原酶中的质子耦合电子传递机制就是分子结构和电子结构控制之间相互作用的例证。我们介绍了数十年来对上述每个系统的研究成果，并阐明了这些金属酶连接蛋白的结构变化与功能结果之间的相互作用。
{"title":"Conformational control over proton-coupled electron transfer in metalloenzymes","authors":"Saman Fatima, Lisa Olshansky","doi":"10.1038/s41570-024-00646-7","DOIUrl":"10.1038/s41570-024-00646-7","url":null,"abstract":"From the reduction of dinitrogen to the oxidation of water, the chemical transformations catalysed by metalloenzymes underlie global geochemical and biochemical cycles. These reactions represent some of the most kinetically and thermodynamically challenging processes known and require the complex choreography of the fundamental building blocks of nature, electrons and protons, to be carried out with utmost precision and accuracy. The rate-determining step of catalysis in many metalloenzymes consists of a protein structural rearrangement, suggesting that nature has evolved to leverage macroscopic changes in protein molecular structure to control subatomic changes in metallocofactor electronic structure. The proton-coupled electron transfer mechanisms operative in nitrogenase, photosystem II and ribonucleotide reductase exemplify this interplay between molecular and electronic structural control. We present the culmination of decades of study on each of these systems and clarify what is known regarding the interplay between structural changes and functional outcomes in these metalloenzyme linchpins. Rate-limiting conformational changes often gate the formation of catalytically active metalloenzyme states. We review examples of the interplay between macroscopic changes in protein molecular structure and subatomic changes in metallocofactor electronic structure that together enable precision control over nature’s redox machines.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"762-775"},"PeriodicalIF":38.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120237","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 : 2024-08-23DOI: 10.1038/s41570-024-00640-z
Abhishek Singh, Payel Parvin, Bapan Saha, Dibyendu Das
The soft and wet machines of life emerged as the spatially enclosed ensemble of biomolecules with replicating capabilities integrated with metabolic reaction cycles that operate at far-from-equilibrium. A thorough step-by-step synthetic integration of these elements, namely metabolic and replicative properties all confined and operating far-from-equilibrium, can set the stage from which we can ask questions related to the construction of chemical-based evolving systems with living matter-like properties — a monumental endeavour of systems chemistry. The overarching concept of this Review maps the discoveries on this possible integration of reaction networks, self-reproduction and compartmentalization under non-equilibrium conditions. We deconvolute the events of reaction networks and transient compartmentalization and extend the discussion towards self-reproducing systems that can be sustained under non-equilibrium conditions. Although enormous challenges lie ahead in terms of molecular diversity, information transfer, adaptation and selection that are required for open-ended evolution, emerging strategies to generate minimal metabolic cycles can extend our growing understanding of the chemical emergence of the biosphere of Earth. The origins of complex life forms from simple chemicals remain one of the most enigmatic mysteries. This Review explores how non-equilibrium chemical-based systems can exhibit living matter-like properties with an outlook that connects the possibility of diversification, adaptation and evolution.
{"title":"Non-equilibrium self-assembly for living matter-like properties","authors":"Abhishek Singh, Payel Parvin, Bapan Saha, Dibyendu Das","doi":"10.1038/s41570-024-00640-z","DOIUrl":"10.1038/s41570-024-00640-z","url":null,"abstract":"The soft and wet machines of life emerged as the spatially enclosed ensemble of biomolecules with replicating capabilities integrated with metabolic reaction cycles that operate at far-from-equilibrium. A thorough step-by-step synthetic integration of these elements, namely metabolic and replicative properties all confined and operating far-from-equilibrium, can set the stage from which we can ask questions related to the construction of chemical-based evolving systems with living matter-like properties — a monumental endeavour of systems chemistry. The overarching concept of this Review maps the discoveries on this possible integration of reaction networks, self-reproduction and compartmentalization under non-equilibrium conditions. We deconvolute the events of reaction networks and transient compartmentalization and extend the discussion towards self-reproducing systems that can be sustained under non-equilibrium conditions. Although enormous challenges lie ahead in terms of molecular diversity, information transfer, adaptation and selection that are required for open-ended evolution, emerging strategies to generate minimal metabolic cycles can extend our growing understanding of the chemical emergence of the biosphere of Earth. The origins of complex life forms from simple chemicals remain one of the most enigmatic mysteries. This Review explores how non-equilibrium chemical-based systems can exhibit living matter-like properties with an outlook that connects the possibility of diversification, adaptation and evolution.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"8 10","pages":"723-740"},"PeriodicalIF":38.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045632","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}
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