ChemPub Date : 2025-09-11DOI: 10.1016/j.chempr.2025.102745
David A. Leigh
{"title":"Reaction: Of myths, misconceptions, and motors—A matter of equilibrium","authors":"David A. Leigh","doi":"10.1016/j.chempr.2025.102745","DOIUrl":"10.1016/j.chempr.2025.102745","url":null,"abstract":"<div><div>David Leigh earned a PhD in crown ether chemistry from the University of Sheffield in 1987 and has held professorial positions at the Universities of Warwick, Edinburgh, Manchester, and East China Normal University. Landmark examples from his laboratory include the introduction of synthetic molecular ratchets and the first catalysis-driven small-molecule motors. The latter were recently used to demonstrate the transduction of chemical energy through motor catalysis, the fundamental process underpinning biology.</div></div>","PeriodicalId":268,"journal":{"name":"Chem","volume":"11 9","pages":"Article 102745"},"PeriodicalIF":19.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043335","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}
ChemPub Date : 2025-09-11DOI: 10.1016/j.chempr.2025.102578
Monika Wenisch , Yinqing Li , Marius G. Braun , Lukas Eylert , Fabian Späth , Simone M. Poprawa , Bernhard Rieger , Christopher V. Synatschke , Henrike Niederholtmeyer , Job Boekhoven
{"title":"Toward synthetic life—Emergence, growth, creation of offspring, decay, and rescue of fuel-dependent synthetic cells","authors":"Monika Wenisch , Yinqing Li , Marius G. Braun , Lukas Eylert , Fabian Späth , Simone M. Poprawa , Bernhard Rieger , Christopher V. Synatschke , Henrike Niederholtmeyer , Job Boekhoven","doi":"10.1016/j.chempr.2025.102578","DOIUrl":"10.1016/j.chempr.2025.102578","url":null,"abstract":"<div><div>The <em>de novo</em> synthesis of life from non-living matter represents a bold scientific challenge, advancing our understanding of life’s minimal requirements and offering revolutionary applications in biotechnology. We explore fuel-dependent synthetic cells based on complex coacervate droplets, which lack membranes and readily take up reactants. Given their fuel-dependent nature, these droplets emerge and grow when fuel is abundant but dissolve under starvation conditions, mimicking the non-equilibrium nature of life. However, their ability to produce offspring—a key requirement for life—has remained elusive. Moreover, their rescue in repetitive fueling-starvation experiments has not been demonstrated. Our work elucidates a mechanism of producing offspring by synthetic cells driven by solid-like speckles in droplets liberated as offspring. By fine-tuning parameters, we control offspring number and survival. Finally, refueling sustains second-generation synthetic cells. This system provides a platform for coupling offspring production with self-replicating molecules, paving the way for synthetic cells capable of Darwinian evolution.</div></div>","PeriodicalId":268,"journal":{"name":"Chem","volume":"11 9","pages":"Article 102578"},"PeriodicalIF":19.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927098","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}
ChemPub Date : 2025-09-11DOI: 10.1016/j.chempr.2025.102596
Dong Yang , Yi Hu , Shuai Liu , Wenhui Yang , Xi Ren , Yanbing Li , Feng Xu , Min Gong , Yunlong Zhao , Xiaozhong Qiu , Honghao Hou
{"title":"Synthesis and assembly strategy of electroactive biomaterials and systems for soft tissue engineering applications","authors":"Dong Yang , Yi Hu , Shuai Liu , Wenhui Yang , Xi Ren , Yanbing Li , Feng Xu , Min Gong , Yunlong Zhao , Xiaozhong Qiu , Honghao Hou","doi":"10.1016/j.chempr.2025.102596","DOIUrl":"10.1016/j.chempr.2025.102596","url":null,"abstract":"<div><div>Soft tissue injuries are a common issue affecting human health, and the extent and duration of injuries often constrain the healing process. Electroactive biomaterials have become a key medium for tissue regeneration by modulating cellular behavior, but a systematic evaluation of their potential and challenges is still limited. This review comprehensively explores electroactive biomaterials, focusing on their chemical synthesis, assembly processes, application potential, challenges faced, and future directions. First, this work elaborates on the unique and innovative features of electroactive biomaterials’ chemical synthesis and preparation techniques. Subsequently, the principles of electroactive devices and their interactions with biological tissues are described to optimize tissue repair. Finally, the application prospects of electrical stimulation technology in soft tissue engineering are explored, emphasizing its role in cell and tissue regeneration and its clinical potential. In conclusion, this review provides theoretical and practical insights into the development and application of electroactive biomaterials.</div></div>","PeriodicalId":268,"journal":{"name":"Chem","volume":"11 9","pages":"Article 102596"},"PeriodicalIF":19.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088048","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}
ChemPub Date : 2025-09-11DOI: 10.1016/j.chempr.2025.102748
Raorao Yang , Liang Zhang
{"title":"Weaving in polyhedra","authors":"Raorao Yang , Liang Zhang","doi":"10.1016/j.chempr.2025.102748","DOIUrl":"10.1016/j.chempr.2025.102748","url":null,"abstract":"<div><div>The programmable design and synthesis of topologically complex architectures through rational ligand engineering open new avenues for exploring the effects and potential applications of entanglements across chemistry, physics, and biology. In this issue of <em>Chem</em>, Fujita, Sawada, and co-workers extend the folding-and-assembly approach to construct an M<sub>60</sub>L<sub>60</sub>-entangled capsid featuring 60 crossings.</div></div>","PeriodicalId":268,"journal":{"name":"Chem","volume":"11 9","pages":"Article 102748"},"PeriodicalIF":19.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cancer nanomedicine: Concepts, promises, and challenges","authors":"Chunlei Zhu , Eduard Preis , Udo Bakowsky , Younan Xia","doi":"10.1016/j.chempr.2025.102706","DOIUrl":"10.1016/j.chempr.2025.102706","url":null,"abstract":"<div><div>Cancer is one of the leading causes of death worldwide. Despite improved understanding and enormous breakthroughs in treatment, ultimately defeating cancer remains challenging. Cancer nanomedicine, one of the most active areas in nanotechnology, focuses on improving the efficacy of chemotherapeutics and/or the imaging capability of diagnostic probes by enabling therapeutic and/or diagnostic functionalities on a nanoscale platform. This review aims to provide a tutorial on the current landscape of cancer nanomedicine. We start with a few biological examples to illustrate the general concept of nanomedicine. We then highlight several major advantages of nanomedicine and explain its significant role in reshaping the pharmaceutical industry. Afterward, we discuss key factors affecting the efficacy of nanomedicines in cancer therapy. We also discuss the primary challenges by focusing on the gap between <em>in vitro</em> and <em>in vivo</em> studies. Finally, we conclude this review by illustrating the opportunities in the rational design of next-generation nanomedicines.</div></div>","PeriodicalId":268,"journal":{"name":"Chem","volume":"11 9","pages":"Article 102706"},"PeriodicalIF":19.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047594","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}
ChemPub Date : 2025-09-04DOI: 10.1016/j.chempr.2025.102714
Solhye Choe, Chaerin Lim, Sunghoon Kang, Eunsung Lee
{"title":"N-Heterocyclic carbene-derived second-period main-group radicals: Synthesis, fundamentals, and applications","authors":"Solhye Choe, Chaerin Lim, Sunghoon Kang, Eunsung Lee","doi":"10.1016/j.chempr.2025.102714","DOIUrl":"https://doi.org/10.1016/j.chempr.2025.102714","url":null,"abstract":"The stabilization of organic radicals has long been a challenge due to their intrinsic reactivity. N-Heterocyclic carbenes (NHCs), with their unique electronic and steric properties, have emerged as powerful tools for stabilizing persistent radicals. This review highlights the latest advancements in carbene-supported organic radicals, covering key structural motifs, electronic properties, and implications for chemical reactivity. We discuss recent breakthroughs in the design of radical species derived from NHCs, cyclic (alkyl)(amino)carbenes (CAACs), and diamidocarbenes (DACs). The relationships among radical stability, spin delocalization, and functional applications are systematically discussed, particularly in the context of redox-active materials, photocatalysis, and electronic devices. This work underscores the broader significance of NHC-stabilized radicals in fundamental chemistry and applied sciences, offering insights into future directions for the field.","PeriodicalId":268,"journal":{"name":"Chem","volume":"34 1","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987614","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}
ChemPub Date : 2025-09-03DOI: 10.1016/j.chempr.2025.102737
Alexander A. Vinogradov, Hiroaki Suga
{"title":"Measuring kcat/KM values for over 200,000 enzymatic substrates with mRNA display","authors":"Alexander A. Vinogradov, Hiroaki Suga","doi":"10.1016/j.chempr.2025.102737","DOIUrl":"https://doi.org/10.1016/j.chempr.2025.102737","url":null,"abstract":"Recent advances in enzymology are enabled by the methods for high-throughput kinetic measurements. Common instrumentation-based techniques can examine thousands of enzymatic reactions in parallel, but scaling the throughput further can be challenging. Here, we establish DOMEK (mRNA-display-based one-shot measurement of enzymatic kinetics), an integrated experimental and computational pipeline for ultra-high-throughput kinetic measurements using mRNA display-derived next-generation sequencing data. The method can accurately determine k<sub>cat</sub>/K<sub>M</sub> specificity constants of post-translational modification enzyme substrates. We benchmark the platform by measuring k<sub>cat</sub>/K<sub>M</sub> values for ∼2.86 × 10<sup>5</sup> peptide substrates of a dehydroalanine reductase and leverage the resulting data to build interpretable models of the substrate fitness landscape. The resulting model accurately decomposes reaction activation energies of a peptide substrate into energetic contributions of individual amino acids to reveal microscopic and macroscopic aspects of the enzyme catalysis. Our results establish a generalizable, enzyme-agnostic framework for scaling kinetic measurements to millions of reactions.","PeriodicalId":268,"journal":{"name":"Chem","volume":"52 1","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modular synthesis of fluoroalkyl-substituted cyclopropenes with fluoroalkylacylsilanes as carbynyl cation equivalents","authors":"Gang Zhou, Yuan Yao, Xiaoqian He, Weilu Zhang, Shanshan Liu, Xiao Shen","doi":"10.1016/j.chempr.2025.102721","DOIUrl":"https://doi.org/10.1016/j.chempr.2025.102721","url":null,"abstract":"The carbynyl cation, which is a reactive species capable of forming three covalent bonds, remains relatively unexplored due to its extreme reactivity and the limited availability of efficient sources. Herein, we report the application of fluoroalkylacylsilanes as carbynyl cation equivalents, enabling the modular synthesis of fluoroalkyl-substituted cyclopropenes, where three new covalent bonds are constructed. The success of this reaction lies in the integration of sequential photocatalysis and acid catalysis in a one-pot process. Photocatalysis facilitates the carbene-mediated [2 + 1] cycloaddition with alkynes, while acid catalysis promotes formal C–O bond functionalization via cyclopropenium intermediates. Using this strategy, we have synthesized a diverse array of fluoroalkylated cyclopropenyl ethers, arenes, alkanes, thioethers, amines, and azides. These reactions are not only effective for the synthesis of simple cyclopropenes but also provide access to complex cyclopropenes that are otherwise challenging to prepare.","PeriodicalId":268,"journal":{"name":"Chem","volume":"45 1","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Construction of chiral nitrogen stereocenters via enantioselective C–H activation","authors":"Zechen Wu, Dongsheng Yi, Junhao Tang, Fanyi Meng, Haining Zhu, Kevin Wu, Kaining Duanmu, Jin-Quan Yu, Yanghui Zhang","doi":"10.1016/j.chempr.2025.102730","DOIUrl":"https://doi.org/10.1016/j.chempr.2025.102730","url":null,"abstract":"Enantioselective C–H activation has recently emerged as a versatile method for selectively constructing point, axial, and planar chirality. Out of the main strategies in asymmetric catalysis, desymmetrization, enantioselection, and classical kinetic resolutions have been demonstrated in C–H activation reactions. To the best of our knowledge, dynamic kinetic resolution (DKR) via enantioselective C(sp<sup>3</sup>)-H activation to set point chirality remains unrealized. While the rapid inversion of nitrogen stereocenters typically presents a challenge to their enantioselective synthesis, this phenomenon provides a unique opportunity to selectively access nitrogen stereocenters via a DKR given the appropriate system. Here, we report the DKR of nitrogen stereocenters via a Pd-catalyzed enantioselective C–H olefination yielding enantioenriched tribenzo[<em>b</em>,<em>d</em>,<em>f</em>]azepines and dibenzo[<em>b</em>,<em>f</em>]azepines, thus demonstrating the feasibility of constructing enantioenriched nitrogen stereocenters by harnessing nitrogen inversion. The chiral tribenzo[<em>b</em>,<em>d</em>,<em>f</em>]azepine products exhibit high circularly polarized luminescence (CPL) performance, representing a novel scaffold for exploration in this area.","PeriodicalId":268,"journal":{"name":"Chem","volume":"52 1","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unexpected diastereoselective chemistry on a 2D protein surface","authors":"Zhong Hui Lim, Zonghua Bo, Emily Armstrong, Hagan Bayley, Yujia Qing","doi":"10.1016/j.chempr.2025.102717","DOIUrl":"https://doi.org/10.1016/j.chempr.2025.102717","url":null,"abstract":"Enantioselective enzymes feature structured catalytic sites positioned within binding pockets. In contrast, widely occurring flat protein surfaces, which have been suggested to have emerged early in ancestral protein evolution as solvent-exposed β sheets, appear unlikely to catalyze asymmetric reactions because they lack the necessary scaffold for interacting with substrates in three dimensions. At the near-flat, water-accessible surface within the α-hemolysin transmembrane pore, we now demonstrate remarkable diastereoselectivity in hemithioacetal formation between a cysteine side chain and a series of aldehyde substrates. After protein surface remodeling by mutagenesis, diastereomeric ratios of up to 95:5 (kinetic control) and 98:2 (thermodynamic control) were achieved with a range of aromatic aldehydes. Molecular dynamics simulations confirmed asymmetric interactions between adducts and nearby side chains in a two-dimensional plane. Our findings indicate that flat protein surfaces can scaffold stereoselective chemistry, thereby expanding the designable protein space for catalyst engineering and providing insight into the origin of selective enzymes.","PeriodicalId":268,"journal":{"name":"Chem","volume":"14 1","pages":""},"PeriodicalIF":23.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928638","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}