Pub Date : 2026-01-19DOI: 10.1038/s41570-025-00791-7
Selma Piranej, Luona Zhang, Alisina Bazrafshan, Wenxiao Deng, Khalid Salaita
DNA nanotechnology has rapidly evolved, leading to the development of dynamic nanoscale and microscale devices that mimic natural molecular machinery. This Review explores the latest advancements in DNA-based machines, motors and switches, emphasizing the need for clear definitions to distinguish between these often-interchanged terms. By analysing key performance metrics such as speed, force generation, efficiency and autonomy, we provide a framework for evaluating these devices against their biological counterparts, including motor proteins such as myosin and kinesin. We highlight innovative design strategies such as strand displacement, DNA origami and hybrid systems, which enhance the functionality of DNA-based constructs and bridge the gap between synthetic and natural systems. These advancements have promising applications in areas such as targeted drug delivery, biosensing and nanofabrication, although challenges in achieving the high performance and efficiency seen in biological systems remain. Through a synthesis of current research, this Review outlines the opportunities and challenges in the development of DNA-based nanoscale and microscale devices.
{"title":"Programming DNA machines to move.","authors":"Selma Piranej, Luona Zhang, Alisina Bazrafshan, Wenxiao Deng, Khalid Salaita","doi":"10.1038/s41570-025-00791-7","DOIUrl":"https://doi.org/10.1038/s41570-025-00791-7","url":null,"abstract":"<p><p>DNA nanotechnology has rapidly evolved, leading to the development of dynamic nanoscale and microscale devices that mimic natural molecular machinery. This Review explores the latest advancements in DNA-based machines, motors and switches, emphasizing the need for clear definitions to distinguish between these often-interchanged terms. By analysing key performance metrics such as speed, force generation, efficiency and autonomy, we provide a framework for evaluating these devices against their biological counterparts, including motor proteins such as myosin and kinesin. We highlight innovative design strategies such as strand displacement, DNA origami and hybrid systems, which enhance the functionality of DNA-based constructs and bridge the gap between synthetic and natural systems. These advancements have promising applications in areas such as targeted drug delivery, biosensing and nanofabrication, although challenges in achieving the high performance and efficiency seen in biological systems remain. Through a synthesis of current research, this Review outlines the opportunities and challenges in the development of DNA-based nanoscale and microscale devices.</p>","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":" ","pages":""},"PeriodicalIF":51.7,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003771","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 : 2026-01-02DOI: 10.1038/s41570-025-00789-1
Pankti Dhumal, Swaroop Chakraborty, Iseult Lynch
Metal–organic frameworks are increasingly used in environmental technologies, whereby their biomolecular coronas determine their identity, transport, persistence and ecosystem effects. We argue that further research is needed to embed corona considerations into framework systems design and regulation, and we outline the minimal, actionable steps needed to achieve this.
{"title":"Biomolecular coronas govern the environmental fate of metal–organic frameworks","authors":"Pankti Dhumal, Swaroop Chakraborty, Iseult Lynch","doi":"10.1038/s41570-025-00789-1","DOIUrl":"10.1038/s41570-025-00789-1","url":null,"abstract":"Metal–organic frameworks are increasingly used in environmental technologies, whereby their biomolecular coronas determine their identity, transport, persistence and ecosystem effects. We argue that further research is needed to embed corona considerations into framework systems design and regulation, and we outline the minimal, actionable steps needed to achieve this.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 2","pages":"89-91"},"PeriodicalIF":51.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889593","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 : 2026-01-02DOI: 10.1038/s41570-025-00788-2
Patrick I. T. Thomson, Alastair W. Wark, Alan R. Kennedy, Fraser J. Scott
Chemistry is an experimental science that for many learners only comes alive in the laboratory. But specialized equipment is increasingly out of reach of school budgets. Strengthening school–university collaborations can help to bridge the gap.
{"title":"Strengthening school–university collaborations","authors":"Patrick I. T. Thomson, Alastair W. Wark, Alan R. Kennedy, Fraser J. Scott","doi":"10.1038/s41570-025-00788-2","DOIUrl":"10.1038/s41570-025-00788-2","url":null,"abstract":"Chemistry is an experimental science that for many learners only comes alive in the laboratory. But specialized equipment is increasingly out of reach of school budgets. Strengthening school–university collaborations can help to bridge the gap.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 2","pages":"97-98"},"PeriodicalIF":51.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889567","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 : 2025-12-15DOI: 10.1038/s41570-025-00779-3
Juncheng Liu, Antonia G. Denkova, Rienk Eelkema
Ionizing radiation-induced drug release is a combined chemoradiation therapy, which aims to reduce the systemic toxicity of chemotherapeutics. Radiation is used for both radiotherapy and to trigger the release of a chemotherapeutic. To understand radiation-induced drug activation and to design new radiation-sensitive chemotherapeutics, it is important to become familiar with the underlying reaction mechanisms. Here, we provide an overview of the crucial process of water radiolysis induced by ionizing radiation and the mechanisms of reactive species generation. We also discuss the reactivity of these species with cellular components and chemical functional groups, to give insight into selective drug activation in complex cellular environments. Finally, we discuss recent progress on radiation-induced drug release focusing on the reaction of water radiolysis products with drug caging groups and the yield of released drugs. We aim to bridge the gap between basic chemical processes in water radiolysis and their relevance for drug release and provide suggestions on the design of radiation-sensitive prodrugs or nanocarriers. This Review explores how ionizing radiation triggers drug release via water radiolysis, detailing reactive species, drug activation mechanisms and strategies for designing radiation-sensitive prodrugs and nanocarriers to enhance chemoradiation therapy with reduced systemic toxicity.
{"title":"The role of ionizing radiation-initiated reactions in targeted activation of chemotherapeutics","authors":"Juncheng Liu, Antonia G. Denkova, Rienk Eelkema","doi":"10.1038/s41570-025-00779-3","DOIUrl":"10.1038/s41570-025-00779-3","url":null,"abstract":"Ionizing radiation-induced drug release is a combined chemoradiation therapy, which aims to reduce the systemic toxicity of chemotherapeutics. Radiation is used for both radiotherapy and to trigger the release of a chemotherapeutic. To understand radiation-induced drug activation and to design new radiation-sensitive chemotherapeutics, it is important to become familiar with the underlying reaction mechanisms. Here, we provide an overview of the crucial process of water radiolysis induced by ionizing radiation and the mechanisms of reactive species generation. We also discuss the reactivity of these species with cellular components and chemical functional groups, to give insight into selective drug activation in complex cellular environments. Finally, we discuss recent progress on radiation-induced drug release focusing on the reaction of water radiolysis products with drug caging groups and the yield of released drugs. We aim to bridge the gap between basic chemical processes in water radiolysis and their relevance for drug release and provide suggestions on the design of radiation-sensitive prodrugs or nanocarriers. This Review explores how ionizing radiation triggers drug release via water radiolysis, detailing reactive species, drug activation mechanisms and strategies for designing radiation-sensitive prodrugs and nanocarriers to enhance chemoradiation therapy with reduced systemic toxicity.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 1","pages":"72-87"},"PeriodicalIF":51.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763292","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 : 2025-12-12DOI: 10.1038/s41570-025-00784-6
Andy Pike, Esther C. Y. Lee, Iacovos N. Michaelides, Markus Schade, Ankit Sharma, James S. Scott, Abhishek Srivastava
Targeted protein degradation has the potential to deliver greater efficacy than conventional receptor antagonists or enzyme inhibitors and address previously undruggable targets. This has driven a recent surge of interest in protein degradation modalities. Bifunctional degraders, specifically proteolysis targeting chimeras (PROTACs), have become a key modality in the protein degrader space, despite the physicochemical challenges they present in achieving oral bioavailability. In this Review, we discuss the lessons learned to date in the optimization of PROTACs, with particular emphasis on the role of the linker region, including its role in optimization of pharmacology, impact on oral bioavailability, and influence on metabolic fate. The evolution from pharmacological tools to an established clinical modality, and the lessons that can be drawn from the preclinical data and the first cohort of PROTACs to reach the clinic, is discussed. Proteolysis targeting chimeras (PROTACs) are an emerging platform in drug discovery with the potential to unlock novel pharmacology and tackle undruggable targets. This Review highlights learnings from the first cohort of clinical-stage PROTACs, which use short, ring-rich linkers, often complemented with one basic centre, to achieve good bioavailability and metabolic stability.
{"title":"Lessons learned in linking PROTACs from discovery to the clinic","authors":"Andy Pike, Esther C. Y. Lee, Iacovos N. Michaelides, Markus Schade, Ankit Sharma, James S. Scott, Abhishek Srivastava","doi":"10.1038/s41570-025-00784-6","DOIUrl":"10.1038/s41570-025-00784-6","url":null,"abstract":"Targeted protein degradation has the potential to deliver greater efficacy than conventional receptor antagonists or enzyme inhibitors and address previously undruggable targets. This has driven a recent surge of interest in protein degradation modalities. Bifunctional degraders, specifically proteolysis targeting chimeras (PROTACs), have become a key modality in the protein degrader space, despite the physicochemical challenges they present in achieving oral bioavailability. In this Review, we discuss the lessons learned to date in the optimization of PROTACs, with particular emphasis on the role of the linker region, including its role in optimization of pharmacology, impact on oral bioavailability, and influence on metabolic fate. The evolution from pharmacological tools to an established clinical modality, and the lessons that can be drawn from the preclinical data and the first cohort of PROTACs to reach the clinic, is discussed. Proteolysis targeting chimeras (PROTACs) are an emerging platform in drug discovery with the potential to unlock novel pharmacology and tackle undruggable targets. This Review highlights learnings from the first cohort of clinical-stage PROTACs, which use short, ring-rich linkers, often complemented with one basic centre, to achieve good bioavailability and metabolic stability.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 2","pages":"117-132"},"PeriodicalIF":51.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743312","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 : 2025-12-10DOI: 10.1038/s41570-025-00787-3
Steven V. Ley, Stephanie Greed
Ahead of his 80th birthday, Steven V. Ley, Professor of Chemistry at the University of Cambridge, discussed his career from drawing chemicals by hand to his work generating complex natural product architectures using machines.
在他80岁生日之前，剑桥大学化学教授Steven V. Ley讨论了他的职业生涯，从手工绘制化学物质到使用机器生成复杂的天然产物结构。
{"title":"A career with a natural interest in total synthesis","authors":"Steven V. Ley, Stephanie Greed","doi":"10.1038/s41570-025-00787-3","DOIUrl":"10.1038/s41570-025-00787-3","url":null,"abstract":"Ahead of his 80th birthday, Steven V. Ley, Professor of Chemistry at the University of Cambridge, discussed his career from drawing chemicals by hand to his work generating complex natural product architectures using machines.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 1","pages":"3-4"},"PeriodicalIF":51.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724698","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 : 2025-12-01DOI: 10.1038/s41570-025-00773-9
Noam Orbach, Zachary P. Sercel, Rahul Suresh, Ilan Marek
Epoxides are ubiquitous synthetic building blocks owing to the numerous tactics for their C–O bond cleavage. Remarkably, epoxides also undergo selective C–C bond cleavage by a broad range of transformations, utilizing orthogonal conditions to override the conventional C–O bond scission. These strategies allow the construction of diverse oxygenated cyclic and acyclic molecular backbones, often challenging to access otherwise. Here, we discuss the various modes of epoxide C–C bond cleavage reactions, highlighting synthetic applications of these reactions and suggesting directions for the further development of these powerful, yet underutilized, methods. Epoxides, which readily undergo C–O bond cleavage, also undergo skeletal rearrangements via C–C bond activation. This Review discusses modes of epoxide C–C bond cleavage and their applications, highlighting the mechanistic features which lead to selective bond scission.
{"title":"Methods and applications for epoxide C–C bond cleavage reactions","authors":"Noam Orbach, Zachary P. Sercel, Rahul Suresh, Ilan Marek","doi":"10.1038/s41570-025-00773-9","DOIUrl":"10.1038/s41570-025-00773-9","url":null,"abstract":"Epoxides are ubiquitous synthetic building blocks owing to the numerous tactics for their C–O bond cleavage. Remarkably, epoxides also undergo selective C–C bond cleavage by a broad range of transformations, utilizing orthogonal conditions to override the conventional C–O bond scission. These strategies allow the construction of diverse oxygenated cyclic and acyclic molecular backbones, often challenging to access otherwise. Here, we discuss the various modes of epoxide C–C bond cleavage reactions, highlighting synthetic applications of these reactions and suggesting directions for the further development of these powerful, yet underutilized, methods. Epoxides, which readily undergo C–O bond cleavage, also undergo skeletal rearrangements via C–C bond activation. This Review discusses modes of epoxide C–C bond cleavage and their applications, highlighting the mechanistic features which lead to selective bond scission.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 1","pages":"31-49"},"PeriodicalIF":51.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645202","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 : 2025-12-01DOI: 10.1038/s41570-025-00786-4
Cesar Augusto Roque-Borda, Fernando Rogério Pavan, Beatriz G. de la Torre, Fernando Albericio
In 2025, peptide research saw the convergence of chemical synthesis and computational modelling. Advances in artificial intelligence-guided design and new macrocyclic and covalent frameworks expanded structural creativity, transforming peptides into programmable molecules with functions beyond traditional design.
{"title":"Redefining peptide chemistry beyond accumulating analogues","authors":"Cesar Augusto Roque-Borda, Fernando Rogério Pavan, Beatriz G. de la Torre, Fernando Albericio","doi":"10.1038/s41570-025-00786-4","DOIUrl":"10.1038/s41570-025-00786-4","url":null,"abstract":"In 2025, peptide research saw the convergence of chemical synthesis and computational modelling. Advances in artificial intelligence-guided design and new macrocyclic and covalent frameworks expanded structural creativity, transforming peptides into programmable molecules with functions beyond traditional design.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 1","pages":"9-11"},"PeriodicalIF":51.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645248","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 : 2025-11-28DOI: 10.1038/s41570-025-00774-8
Weizhong Tian, Rui Wang, Deren Yang, Jingjing Xue
Perovskite solar cells (PSCs) are a game-changing photovoltaic technology that can be processed from solutions. Molecular engineering of organic A-cations has become paramount to the rapid development of PSCs as they influence the molecular structure of thin films and interfaces. The rich selectivity and designability of organic A-cations offer immense opportunities to regulate various properties of metal halide perovskites (MHPs) through chemical interactions. In this Review, we discuss the roles of organic A-cations in MHPs, providing insight into the structure–interaction–property relationships. We show how the molecular structures of A-cations affect chemical interactions in perovskites, and how these interactions affect the overall properties of PSCs. First, we introduce the impact of organic A-cations and their bonds in MHPs and then explore their roles from the lattice and electronic levels through to crystal growth, stability, defects, charge-carrier transport and band-edge states. Prospects for future research directions, opportunities and challenges are also discussed. The roles of organic A-cations in halide perovskite photovoltaics are discussed from a molecular point of view by considering their chemical, lattice and electronic interactions. Prospects for future research directions, opportunities and challenges are also presented.
{"title":"Organic A-cations in metal halide perovskite photovoltaics","authors":"Weizhong Tian, Rui Wang, Deren Yang, Jingjing Xue","doi":"10.1038/s41570-025-00774-8","DOIUrl":"10.1038/s41570-025-00774-8","url":null,"abstract":"Perovskite solar cells (PSCs) are a game-changing photovoltaic technology that can be processed from solutions. Molecular engineering of organic A-cations has become paramount to the rapid development of PSCs as they influence the molecular structure of thin films and interfaces. The rich selectivity and designability of organic A-cations offer immense opportunities to regulate various properties of metal halide perovskites (MHPs) through chemical interactions. In this Review, we discuss the roles of organic A-cations in MHPs, providing insight into the structure–interaction–property relationships. We show how the molecular structures of A-cations affect chemical interactions in perovskites, and how these interactions affect the overall properties of PSCs. First, we introduce the impact of organic A-cations and their bonds in MHPs and then explore their roles from the lattice and electronic levels through to crystal growth, stability, defects, charge-carrier transport and band-edge states. Prospects for future research directions, opportunities and challenges are also discussed. The roles of organic A-cations in halide perovskite photovoltaics are discussed from a molecular point of view by considering their chemical, lattice and electronic interactions. Prospects for future research directions, opportunities and challenges are also presented.","PeriodicalId":18849,"journal":{"name":"Nature reviews. Chemistry","volume":"10 1","pages":"50-71"},"PeriodicalIF":51.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611436","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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