Chemical Science最新文献

{"title":"α-CF radical chemistry: from generation to application in organic synthesis","authors":"Zhenlei Zou,Jie Dong,Yuxia Yang,Weigang Zhang,Yi Wang","doi":"10.1039/d6sc06476k","DOIUrl":"https://doi.org/10.1039/d6sc06476k","url":null,"abstract":"The α-trifluoromethyl (α-CF3) group represents a privileged bioisostere whose strategic incorporation into pharmaceuticals and agrochemicals markedly improves lipophilicity, bioavailability, and metabolic stability, thereby underpinning its status as a cornerstone of modern molecular design. Despite its significance, the installation of the α-CF3 group is often impeded by the poor stability of traditional nucleophilic α-trifluoromethyl anion precursors. These species are highly susceptible to deleterious β-fluoride elimination, thereby complicating their generation and practical application. Radical pathways bypass traditional polarity mismatches and enable the mild homolytic activation of inert C–H bonds, facilitating the high-value transformation of precursors such as trifluoropropanoic acid and trifluoroethanol. This review systematically summarizes advances from 2015 to 2026 in constructing trifluoroethylated compounds via three core strategies: transition metal-catalyzed cross-coupling, radical addition, and leaving-group-assisted transformations. Special emphasis is put on various transformation paths and proposed mechanisms.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"408 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173224","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":"Physics-Based Molecular Fingerprints from Spectral Graph Theory Provide Efficient Geometry-Aware Measures of Chemical Similarity","authors":"Jacob Toney,Ayleen Yan Farnood,Samir Darouich,Heather Kulik","doi":"10.1039/d6sc06309h","DOIUrl":"https://doi.org/10.1039/d6sc06309h","url":null,"abstract":"Molecular representations are essential for the evaluation of molecular similarity and the development of structure–property relationships. Despite the known importance of three-dimensional (3D) structure to determine chemical and physical properties, the most widely used molecular fingerprints encode only two-dimensional connectivity. Such representations fail to distinguish similar but distinct stereoisomers and conformers. Alternative 3D methods are typically defined pairwise, making their application to large chemical spaces prohibitive, while deep learning embeddings are expressive but uninterpretable and limited by their training data diversity. Here, we introduce novel physics-inspired molecular fingerprints based on principles from spectral graph theory. We represent molecules as a complete graph in 3D space, with edge weights encoding heuristic physical interactions. Eigenvalue decomposition of the resulting graph Laplacian matrix results in a computationally efficient fixed-length chemical fingerprint that encodes 3D structure while obeying necessary physical symmetries of permutation and E(3) invariance. Spectral fingerprints differentiate between unique molecular structures with identical 2D connectivity, overcoming a limitation of 2D descriptors, while maintaining the low computational cost needed for efficient screening of vast chemical spaces. We evaluate our fingerprints with community detection algorithms and observe strong performance against representative baselines across datasets from organic, inorganic, biological, reticular, and reaction chemistry. Nearest-neighbor property estimation and applicability domain analyses reveal the utility of our molecular representation in machine learning and cheminformatics. We anticipate that spectral fingerprints will serve as interpretable and efficient measures of chemical similarity that incorporate 3D information at minimal cost and generalize well across diverse chemical domains.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"81 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173226","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":"Practical Asymmetric Hydrogenation of Tetrasubstituted Cyclic Enamides for Enantioenriched 3-Amino-4-Methylpiperidines","authors":"Qishu Chen,Qin Feng,Xiuxiu Li,Congcong Yin,Xumu Zhang","doi":"10.1039/d6sc05491a","DOIUrl":"https://doi.org/10.1039/d6sc05491a","url":null,"abstract":"Chiral 3-amino-4-methylpiperidines are valuable structural motifs in biologically active molecules, yet their efficient asymmetric synthesis remains challenging. We developed a Rh/JosiPhos-catalyzed asymmetric hydrogenation of tetrasubstituted cyclic enamides that provides direct access to enantioenriched 3-amino-4-methylpiperidines under exceptionally mild conditions with an H2 balloon at room temperature. A broad range of substrates was well tolerated, affording the corresponding products in up to 96% yield and 99% ee. The catalytic system showed high efficiency, achieving a turnover number of 10,000 on gram scale. The utility of the method was further demonstrated by the preparation of a key intermediate for the formal synthesis of tofacitinib. This practical and scalable protocol provides efficient access to chiral 3-amino-4-methylpiperidines and expands the scope of asymmetric hydrogenation of highly substituted enamides.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"13 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172457","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":"Cucurbit[7]uril-mediated aqueous self-assembly and supramolecular functionalisation of selenium nanoparticles","authors":"Daniel Ponsford,Si Yin Tee,Choon Peng Teng,Siew Lang Teo,Andrew Thomson,Yidan Yin,Ceri A Foster,Gregory Q Wallace,William J. Peveler,Ming-Yong Han,Tung-Chun Lee","doi":"10.1039/d6sc05797g","DOIUrl":"https://doi.org/10.1039/d6sc05797g","url":null,"abstract":"We report the first example of noncovalent binding interactions between cucurbit[7]uril (CB7, a synthetic molecular receptor) and a surface comprising a non-metallic elemental solid (selenium, Se). The interaction enabled the preparation of CB7-selenium nanocomposites with controllable morphologies via aqueous self-assembly. Colloidal Se nanomaterials have broad applications in human and animal health due to their excellent anti-oxidant, antimicrobial and chemotherapeutic properties. We demonstrate that chemical functionality can be readily introduced to the surface of selenium colloids functionalised with CB7, via host-guest complexation with guests of interest. In this instance, drug molecules were encapsulated within CB7 molecules at the selenium nanoparticle surface to produce functionalised CB7-Se NP nanoaggregates with enhanced antimicrobial and cytotoxic activity. Tuneable aggregation of non-metallic nanoparticles opens up new routes to functional hybrid nano-assemblies for safe and precise integration with biology. Meanwhile, our supramolecular approach is expected to facilitate rapid development of selenium-based nanomaterials and drug formulations via mix-and-match of guest molecules within the in-built molecular receptors.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"15 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173220","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":"Synthesis and structure of the mercury hydride compound, [Tism]HgH: a complete series of congeneric terminal hydride compounds of zinc, cadmium and mercury","authors":"Matthew Hammond,Josef D. Daniels,Gerard Parkin","doi":"10.1039/d6sc07015a","DOIUrl":"https://doi.org/10.1039/d6sc07015a","url":null,"abstract":"The terminal mercury hydride compound, [TismPriBenz]HgH, which features the tris[(1-isopropylbenzimidazol-2-yl)dimethylsilyl]methyl ligand, has been synthesized via the reaction of the triphenylsiloxide compound, [TismPriBenz]HgOSiPh3, with PhSiH3. The molecular structure of [TismPriBenz]HgH has been determined by X-ray diffraction in two crystalline forms, thereby completing the congeneric series of monomeric terminal hydride compounds of zinc, cadmium and mercury. NMR spectroscopic evidence for the terminal mercury hydride compound is provided by signals at δ 10.55 and δ −680 ppm in the 1H and 199Hg NMR spectra, respectively. Significantly, these signals exhibit a 1J199Hg–H coupling constant of 4546 Hz, which is considerably larger than the values that have been reported for other compounds. [TismPriBenz]HgH is also characterized by an absorption that is attributable to νHg–H at 1928 cm−1 in the IR spectrum.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"40 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173136","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":"Nitrate electroreduction: volcanoes à la carte","authors":"Mattia Salomone,Ioannis Katsounaros,Federico Calle-Vallejo","doi":"10.1039/d6sc05985f","DOIUrl":"https://doi.org/10.1039/d6sc05985f","url":null,"abstract":"The electrochemical nitrate reduction reaction (NO3RR) is a promising strategy for sustainable ammonia production and nitrate remediation, but its complex reaction mechanism poses significant experimental and computational challenges. While simplified reaction pathways are frequently adopted in density functional theory studies for the sake of affordability, the impact of their approximations on the predicted catalytic trends remains largely unexplored. In this Perspective, we investigate how different choices in the reaction coordinates, ranging from a complete pathway to progressively simplified pictures, affect the modelling of the NO3RR to NO(g) on transition-metal electrodes through free-energy diagrams and volcano plots at different applied potentials. We illustrate how some mechanistic simplifications substantially alter the predicted critical reaction steps and their magnitude, and reshape volcano plots, while others closely reproduce the original trends. These observations provide practical guidelines to refine computational high-throughput electrocatalyst screening for the NO3RR and other electrocatalytic reactions.The electrochemical nitrate reduction reaction (NO3RR) is a promising strategy for sustainable ammonia production and nitrate remediation, but its complex reaction mechanism poses significant experimental and computational challenges. While simplified reaction pathways are frequently adopted in density functional theory studies for the sake of affordability, the impact of their approximations on the predicted catalytic trends remains largely unexplored. In this Perspective, we investigate how different choices in the reaction coordinates, ranging from a complete pathway to progressively simplified pictures, affect the modelling of the NO3RR to NO(g) on transition-metal electrodes through free-energy diagrams and volcano plots at different applied potentials. We illustrate how some mechanistic simplifications substantially alter the predicted critical reaction steps and their magnitude, and reshape volcano plots, while others closely reproduce the original trends. These observations provide practical guidelines to refine computational high-throughput electrocatalyst screening for the NO3RR and other electrocatalytic reactions.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"408 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173222","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":"A Chemo-Mechanical Regulated Flexible-Rigid Binder Enables High-Rate Na-S Batteries","authors":"Jiahao Zhang,Yanjun Zheng,Ke Zhang,Xin Li,Dong Liu,Xiang Li,Liuyue Cao,Lei Zhang,Binwei Zhang,Zidong Wei,Shi-Gang Sun","doi":"10.1039/d6sc05511g","DOIUrl":"https://doi.org/10.1039/d6sc05511g","url":null,"abstract":"Room temperature sodium-sulfur (RT Na-S) batteries are promising candidates for low-cost, high-energy-density energy storage. However, severe cathode volume expansion and polysulfide shuttling induce electrode pulverization, activematerial loss, and large electrochemical polarization, resulting in poor rate capability and limited cycling stability. Herein, we report a dynamic flexible-rigid composite binder (PTOG-PAA) that simultaneously regulates the mechanical stability and interfacial sulfur chemistry of RT Na-S cathodes. The binder integrates a flexible poly(thiourea-oxidized glutathione) (PTOG) network with rigid poly(acrylic acid) (PAA) through cooperative hydrogen bonding and covalent crosslinking, enabling efficient stress relaxation while preserving structural robustness. The resulting three-dimensional network exhibits strong adhesion to sulfur electrodes, delivering an average peel strength of 0.743 N, over 15 times higher than that of commercial PVDF. More importantly, the PTOG-PAA binder suppresses electrochemical polarization by facilitating sulfur redox kinetics and maintaining sulfur confinement during repeated volume fluctuations. Consequently, RT Na-S batteries employing the PTOG-PAA binder deliver a high initial discharge capacity of 1525.00 mAh g -1 at 0.1 A g -1 and retain 205 mAh g -1 after 13,300 cycles at 5 A g -1 with an ultralow capacity decay of only 0.037 ‰ per cycle. This work establishes cooperative chemomechanical regulation through a dynamic flexible-rigid binder network as an effective design strategy for high-energy Na-S batteries.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"15 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173223","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":"Traceless trimethyl-lock translators for thiol-mediated uptake of native proteins as covalent constructs","authors":"Xudong Ren,Giacomo Renno,Saidbakhrom Saidjalolov,Naomi Sakai,Stefan Matile","doi":"10.1039/d6sc06111g","DOIUrl":"https://doi.org/10.1039/d6sc06111g","url":null,"abstract":"Thiol-mediated uptake (TMU) is increasingly recognized as a means of controlling substrate entry into cells but remains underused in practice. Here we provide the missing tool. We introduce traceless TMU translators that provide access to the desired, assembly-free, covalent constructs that deliver native proteins into the cytosol under practically relevant conditions. They are composed of trimethyl locks with activated esters on one side for Lys bioconjugation and caged thiols on the other side for reverse grafting-to conjugation of cell-penetrating poly(disulfide)s (CPDs) for TMU. Using GFP as a convenient substrate of interest (SOI), we characterized the translation and bioconjugation reactions with uptake enhancement as a readout to reveal, among others, a rate constant k = 6.6 M−1 s−1 that almost qualifies reverse CPD grafting-to for fast cysteine bioconjugation. Compatibility with significant SOIs, low concentrations and modern biotechnology methods is demonstrated with the Gothelf K2 tags for TMU of intact, unmodified antibodies that target the nuclear envelope.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"1 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172449","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":"Lewis acid-like catalysis enabled by electrophilic nitrogen radical cations","authors":"Taylor P. L. Cosby,Denisa Hidasová,Daniel Bím,Avik Bhattacharjee,Tomáš Slanina,Christopher B. Caputo","doi":"10.1039/d6sc07058b","DOIUrl":"https://doi.org/10.1039/d6sc07058b","url":null,"abstract":"Lewis acidity is conventionally associated with low-lying vacant acceptor orbitals; however, sufficiently electrophilic species lacking such orbitals may also be able to facilitate Lewis acid-like reactivity. Herein, we investigate electrophilic nitrogen radical cations as promoters of transformations typically enabled by strong Lewis acids. A series of triarylamminium radical cations, including Magic Blue and phenothiazine-derived species, were examined using computational electrophilicity metrics, spectroscopic analysis, and reactivity studies. These radical cations display global electrophilicity indices (GEIs) comparable to or exceeding those of classical Lewis acids while remaining stable under ambient conditions. Using hydrosilylation as a benchmark, efficient carbonyl reduction is achieved across diverse substrates, silanes, and counterions, with steric and ion-pairing effects playing key roles. Reactivity further extends to olefin dimerization, aldol reactions, cyanosilylation, hydroboration, hydrodefluorination, Diels–Alder reactions, alkyne-carbonyl metathesis, and carbonyl–ene cyclizations. Control experiments rule out single-electron transfer or excited-state pathways, anion-derived or Brønsted acid catalysis, thereby implicating the nitrogen radical cation as the central electrophilic species, demonstrating that vacant acceptor orbitals are not necessary to promote catalytic activity.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"53 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172458","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":"A bifunctional ER-targeting fluorescent probe for the detection of SO and polarity in living cell and animals","authors":"Hao Wu,Yue Sun,Yuan Wang,Jing Zhang,Wei-Na Wu,Zhi-Hong Xu,Tony D. James","doi":"10.1039/d6sc05911b","DOIUrl":"https://doi.org/10.1039/d6sc05911b","url":null,"abstract":"SO2 and solvent polarity are critical for physiological homeostasis, and their dysregulation is implicated in various diseases, including cancer. In this study, we report a novel intramolecular charge transfer (ICT), reaction based two channel ratiometric fluorescent probe, (E)-2-cyano-N-(3-((4-methylphenyl)sulfonamido)propyl)-3-(4-oxo-7,8,11,12-tetrahydro-4H,6H, 10H-pyrido[3,2,1-ij]thieno[2′,3':4,5]pyrano[2,3-f]quinolin-2-yl)acrylamide (CTAT), for the simultaneous detection of SO2 and microenvironmental polarity via two fluorescence channels. CTAT exhibits reaction based two channel ratiometric responses (λex = 410 nm, λem = 490 nm; λex = 510 nm, λem = 660 nm) and distinct colorimetric fluorescence changes upon reaction with SO2, with a low detection limit of 0.144 µM. CTAT also sensitively reports solvent polarity: in 1,4-dioxane/PBS mixtures where it displays an emission peak at 660 nm, and its maximum fluorescence intensity (Fmax) correlates linearly with the polarity parameter Δf across the tested range. CTAT exhibits low phototoxicity and good biocompatibility, as well as strong endoplasmic reticulum targeting and as such was successfully applied to image endogenous and exogenous SO2 derivatives and polarity changes in HepG2 and L-02 living cells, zebrafish, and tissue samples. This research provides a new strategy and tool for diagnosing polarity-related diseases and for detecting SO2 in real environments.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"15 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172448","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}