Chemical Science最新文献

{"title":"Endoplasmic reticulum-targeting activatable nanophotosensitizers for hypoxia relief and enhanced photodynamic therapy","authors":"Shanchao Diao, Xiaowen He, Ying Wu, Likun Yin, Yuxin Huang, Wen Zhou, Chen Xie, Quli Fan","doi":"10.1039/d5sc00534e","DOIUrl":"https://doi.org/10.1039/d5sc00534e","url":null,"abstract":"Photodynamic therapy (PDT) is a promising cancer therapeutic modality. However, the specific targeting capability of conventional photosensitizers is relatively low, which significantly suppresses the efficacy of PDT. In this study, an endoplasmic reticulum (ER)-targeting nanophotosensitizer (TPPa-Y NP) was designed and prepared for enhanced PDT. TPPa-Y NP is prepared by encapsulating an ER-targeting pheophorbide-a (TPPa) and a hypoxia inducible factor 1α (HIF-1α) inhibitor (YC-1) with a hydrogen peroxide (H2O2) responsive amphiphilic copolymer (PEG-PMPAP). After being internalized into tumor cells, TPPa-Y NPs may rapidly dissociate and release both TPPa and YC-1. TPPa can target ER, which leads to the enhance of its fluorescence signal and PDT efficacy. On the other hand, YC-1 may effectively inhibit the overexpressed HIF-1α and alleviate tumor hypoxia, which can further enhance the PDT efficacy of TPPa. Both in vitro and in vivo studies demonstrate that TPPa-Y NPs have better anticancer effect than the nanoparticles without YC-1 (TPPa NPs). Therefore, this study provides a smart nanophotosensitizer which is able to target ER and alleviate hypoxia for PDT efficacy enhancement.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"110 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910371","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 Platform for SpyCatcher Conjugation to Native Antibodies","authors":"Soňa Krajčovičová, Thomas Wharton, Claudia L. Driscoll, Thomas A King, Mark R. Howarth, David R Spring","doi":"10.1039/d5sc02286j","DOIUrl":"https://doi.org/10.1039/d5sc02286j","url":null,"abstract":"Protein-antibody conjugates represent major advancements in targeted therapeutics. However, platforms enabling ‘off-the shelf’ antibody conjugation are seldom reported. The SpyTag/SpyCatcher system, known for its stable isopeptide bond formation, is widely used to engineer protein architectures and study protein folding. This work introduces the fusion of SpyCatcher with native antibodies using cysteine-reactive tetra-divinylpyrimidine (TetraDVP)-SpyTag linkers. This platform allows for the rapid and stable conjugation of a native antibody with SpyCatcher proteins. As a proof of concept, the HER2-targeting antibody trastuzumab was conjugated to different SpyCatcher proteins using a TetraDVP-SpyTag linker, producing robust conjugates that retained specific binding to HER2-positive cells with excellent conversion rates. To demonstrate the platform’s broader applicability, the TetraDVP-SpyTag linker was successfully conjugated to additional native IgG1 and IgG4 antibodies (durvalumab, brentuximab, cetuximab, and gemtuzumab) with similarly high efficiency than trastuzumab. Moreover, a scalable solid-phase synthesis of TetraDVP linkers has been developed, achieving high yields and purity. This innovative platform enables precise, single-step antibody bioconjugation, offering strong potential for protein-antibody conjugate synthesis. With applications across therapeutics and diagnostics, this method advances antibody-based drug development.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"46 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910370","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":"Expanding the Toolbox for Supramolecular Chemistry: Probing Host-Guest Interactions and Binding with in situ FTIR Spectroscopy","authors":"Michael D Pluth, Darren Johnson, Shiva Moaven, Douglas A Vander Griend","doi":"10.1039/d5sc01329a","DOIUrl":"https://doi.org/10.1039/d5sc01329a","url":null,"abstract":"Association constant (<em>K</em><small>_a</small>) measurements provide fundamental information on host-guest interactions in supramolecular chemistry and other areas of science. Here we report the use of <em>in situ</em> FTIR spectroscopy to measure the <em>K</em><small>_a</small> values across three classes of host-guest complexes that involve hydrogen bonding and halogen bonding. This approach can be performed with minimal sample preparation, does not require deuterated solvents, can measure association based on changes in host or guest vibrations, and benefits from a much shorter timescale than NMR spectroscopy. Due to its fast timescale, FTIR spectroscopy also provides details on host/guest conformational changes, such as the presence of unsymmetrical host conformations that are not in the ideal binding conformation until treatment with a suitable guest. These changes would not be observable by standard time-averaged NMR titration measurements. Using this approach, we demonstrated the capabilities and challenges of this technique to investigate host-guest interactions of three anion receptors that use hydrogen or halogen bonding with both mono- and polyatomic anions. In addition to directly observing how host-guest interactions impact bonding within the individual molecules, we also demonstrate that global fitting of the FTIR spectra is an effective and robust approach to measure <em>K</em><small>_a</small> values of these host-guest complexes. We anticipate that this method will provide a new and useful approach to investigating the dynamics and specific interactions across broad areas of science.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"69 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910198","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":"Advances in sulfonyl exchange chemical biology: Expanding druggable target space","authors":"Lyn H Jones","doi":"10.1039/d5sc02647d","DOIUrl":"https://doi.org/10.1039/d5sc02647d","url":null,"abstract":"Targeted covalent inhibitors possess advantages over reversible binding drugs, that includes higher potency, enhanced selectivity and prolonged pharmacodynamic duration. The standard paradigm for covalent inhibitor discovery relies on the use of α,β-unstaurated carbonyl electrophiles to engage the nucleophilic cysteine thiol, but due to its rarity in binding sites, the amino acid is often not available for targeting. 10 years ago we highlighted the emerging potential of sulfonyl fluoride chemical probes that were initially found to serendipitously modify residues beyond cysteine, including tyrosine, lysine, histidine, serine and threonine. Since then, the rational application of sulfonyl fluorides and related sulfonyl exchange warheads to site-specifically target diverse amino acid residues in proteins using small molecules, oligonucleotides, peptides and proteins, has made considerable progress, which has significantly advanced covalent therapeutic discovery. Additionally, sulfonyl exchange chemistry has recently shown utility in the labeling of RNA and carbohydrates, further expanding the biomolecular diversity of addressable targets. This Perspective provides not only a timely update regarding this exciting area of research, thus serving as a useful resource to scientists working in the field, but areas of challenge and opportunity are highlighted that may stimulate new research at the chemistry-biology interface.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"2 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910195","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":"Unveiling the Covalency of Versatile Pu(III)–N bonds in a Unique Plutonium(III) Complex","authors":"Zhuanling Bai, Madeline C. Martelles, Joseph M. Sperling, Thomas E. Albrecht","doi":"10.1039/d5sc01808k","DOIUrl":"https://doi.org/10.1039/d5sc01808k","url":null,"abstract":"A trivalent plutonium-pyrizinyl-tetrazolate complex Na<small>₂</small>[Pu(Hdtp)(dtp)<small>₂</small>(H<small>₂</small>O)<small>₄</small>]·9H<small>₂</small>O (<strong>Pu_dtp</strong>, H<small>₂</small>dtp = 2,3-di-1H-tetrazol-5-ylpyrazine) was synthesized through metathesis reaction of plutonium bromide and Na<small>₂</small>(dtp)·2H<small>₂</small>O in water. This structure is particularly notable among complexes formed by trivalent <em>f</em>-elements and the dtp<small>²⁻</small> ligand in aqueous media. In contrast to other trivalent <em>f</em>-elements, including all Ln<small>³⁺</small> (with the exception of Pm<small>³⁺</small>) and Cm<small>³⁺</small>, preferentially coordinated with eight water molecules rather than the nitrogen donors of the dtp<small>²⁻</small> ligand, Pu<small>³⁺</small> exhibits a distinct affinity for nitrogen coordination. This observation provides strong evidence that the 5<em>f</em> electrons in Pu<small>³⁺</small> are more delocalized than other studied trivalent <em>f</em>-elements, consistent with Hard-Soft Acid-Base theory. In <strong>Pu_dtp</strong>, three distinct Pu(III)–N bonds are present: one Pu(III)–N5 from pyrazinyl, one Pu(III)–N4 from the least electronegative nitrogen in the tetrazolate, and three Pu(III)–N1/N2/N3 from the most electronegative nitrogens in the tetrazolate. Experimental Pu(III)–N bond lengths, Wiberg bond indices (WBI), natural localized molecular orbitals (NLMO), Quantum Theory of Atoms in Molecules (QTAIM), and energy decomposition analysis (EDA), reveal a covalency trend: Pu(III)–N from the most electronegative nitrogen in tetrazolate &gt; Pu(III)–N from the least electronegative nitrogen in tetrazolate &gt; Pu(III)–N from pyrazinyl. This trend arises from the increased negative charge on the most electronegative nitrogen atoms in the tetrazolate ring, enhancing electrostatic Pu−N1/N2/N3 interactions. These stronger interactions promote better orbital overlap, leading to greater covalency compared to the less electronegative nitrogen in tetrazolate (Pu−N4) and the neutral pyrazinyl nitrogen (Pu−N5).","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"25 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915869","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":"Rhenium coordination-induced conformational modulation in nitrogen-doped nanographene","authors":"Eldhose V. Varghese, Yi-Hung Liu, Hsing-Yin Chen, Chien-Hung Li, Chia-Hsiang Chen","doi":"10.1039/d5sc02827b","DOIUrl":"https://doi.org/10.1039/d5sc02827b","url":null,"abstract":"The conformation of nanographene plays a pivotal role in determining its electronic, mechanical, and optical properties. Analyzing the conformation of nanographene is crucial because of its significant implications in various scientific and technological domains. In this work, we examined the changes in the structural conformation of nanographene upon coordination with a metal. We synthesized a series of nitrogen-doped nanographenes (<strong>2</strong>, <strong>3</strong>, and <strong>4</strong>) that differed by one C–C bond and their corresponding nanographene–Re complexes (<strong>2Re</strong>, <strong>3Re</strong>, and <strong>4Re</strong>). The conformations of the metal complexes were thoroughly analyzed using various spectroscopic techniques. A comparison of the X-ray crystal structures of nanographene before and after rhenium coordination revealed that rhenium coordination induced conformational changes in the nanographene moiety. Additionally, we assessed the catalytic activity of the nanographene–Re complexes toward the electrocatalytic hydrogen evolution reaction (HER). In the presence of a small amount of weak acid (1.5 mM acetic acid), the nanographene–Re complex exhibited hydrogen production at a low overpotential of 133 mV.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"8 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910197","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":"Electronic states and contact ion pair formation in lithium-ion electrolytes investigated by far-ultraviolet spectroscopy and quantum chemical calculations.","authors":"Hitomi Sato, Nami Ueno, Ichiro Tanabe","doi":"10.1039/d5sc02406d","DOIUrl":"https://doi.org/10.1039/d5sc02406d","url":null,"abstract":"<p><p>The electronic states of lithium-ion (Li⁺) electrolytes play a crucial role in understanding their solvation structures and electronic interactions. In this study, far-ultraviolet (FUV) spectroscopy and quantum chemical calculations were used to investigate lithium bis(trifluoromethanesulfonyl)imide (TFSI)-based electrolytes dissolved in dimethyl carbonate (DMC). At low Li⁺ concentrations, the absorption spectra exhibited a redshift, which was attributed to electronic interactions between Li⁺ and DMC in the solvation structure. In contrast, at high concentrations, a clear blueshift was observed. Quantum chemical calculations revealed that this blueshift originates from the formation of contact ion pairs, leading to intermolecular electronic excitation and electron transfer between the TFSI anion and DMC. These findings indicate that the nature of electronic transitions in the FUV region changes significantly with the ionic environment. The results demonstrate that FUV spectroscopy is a powerful technique for probing dynamic changes in solvation and ion association states in electrolytes, offering valuable guidance for the design and optimization of battery materials.</p>","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076308","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}

{"title":"Stereoselective synthesis of heterocyclic tetraphenylethylene analogues with configuration-dependent solid-state luminescence.","authors":"Mathilde Seinfeld, Jean Rouillon, Raphael Rullan, Erwann Jeanneau, Stephan N Steinmann, Chantal Andraud, Tangui Le Bahers, Cyrille Monnereau","doi":"10.1039/d4sc08333d","DOIUrl":"https://doi.org/10.1039/d4sc08333d","url":null,"abstract":"<p><p>While nowadays ubiquitous in a variety of optoelectronic applications, fluorophores displaying aggregation induced emission (AIE) and in particular those constructed around the tetraphenylethylene (TPE) core suffer severe limitations. In particular, it has been reported in many instances that stereoconfiguration around the central double bond may severely impact the solid-state luminescence properties (maximal emission wavelength and fluorescence quantum yield). Stereoselective synthesis of extended TPE cores remains challenging, and separation of diastereoisomer mixtures is generally tedious. In this paper, we introduce ditriazolostilbene moities (DTS) as an alternative to TPE. DTS offers two significant advantages over its TPE counterpart: firstly, a fully stereoselective synthesis of the (<i>E</i>)-isomer, and secondly, the use of a copper-catalyzed azide-alkyne cycloaddition (CuAAc) reaction in the final step, which simplifies access to novel derivatives. We illustrate the benefits of this approach using stereopure and (<i>E</i>) and (<i>Z</i>)-aggregates, powders and crystals of the molecule and show that emission properties are considerably dependent on their stereoconfiguration.</p>","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076312","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}

{"title":"Ability of strained C atoms to act as an electron donor.","authors":"Mariusz Michalczyk, Wiktor Zierkiewicz, Steve Scheiner","doi":"10.1039/d5sc01632k","DOIUrl":"https://doi.org/10.1039/d5sc01632k","url":null,"abstract":"<p><p>There is a great deal of strain within the propellane and pyramidane hydrocarbon molecules. Quantum chemical calculations evaluate how this strain affects the ability of the bridgehead C atom to act as an electron donor in hydrogen, halogen, chalcogen, pnicogen, and tetrel bonds, despite the absence of a formal C lone pair or C[double bond, length as m-dash]C multiple bond. The strain induces the formation of a substantial region of negative electrostatic potential on this C atom which can attract the σ-hole of an electrophile. Each such molecule also contains an occupied molecular orbital that can be described as either a C lone pair or C-C bond, which is spatially disposed to align with, and transfer charge to, a σ* antibonding orbital of an approaching Lewis acid. The degree of strain within the hydrocarbon is closely correlated with the magnitude of the negative electrostatic potential, which is in turn connected with the strength of the ensuing bond. Tetrel bonds are strongest, followed by halogen, both of which contain a significant degree of covalency.</p>","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076306","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}

{"title":"Tandem-repeat proteins introduce tuneable properties to engineered biomolecular condensates.","authors":"Tin Long Chris Ng, Mateo P Hoare, M Julia Maristany, Ellis J Wilde, Tomas Sneideris, Jan Huertas, Belinda K Agbetiameh, Mona Furukawa, Jerelle A Joseph, Tuomas P J Knowles, Rosana Collepardo-Guevara, Laura S Itzhaki, Janet R Kumita","doi":"10.1039/d5sc00903k","DOIUrl":"https://doi.org/10.1039/d5sc00903k","url":null,"abstract":"<p><p>The cell's ability to rapidly partition biomolecules into biomolecular condensates is linked to a diverse range of cellular functions. Understanding how the structural attributes of biomolecular condensates are linked with their biological roles can be facilitated by the development of synthetic condensate systems that can be manipulated in a controllable and predictable way. Here, we design and characterise a tuneable synthetic biomolecular condensate platform fusing modular consensus-designed tetratricopeptide repeat (CTPR) proteins to intrinsically-disordered domains. Trends between the CTPR structural attributes and condensate propensity were recapitulated across different experimental conditions and by <i>in silico</i> modelling, demonstrating that the CTPR domain can systematically affect the condensates in a predictable manner. Moreover, we show that incorporating short binding motifs into the CTPR domain results in specific target-protein recruitment into the condensates. Our model system can be rationally designed in a versatile manner to both tune condensate propensity and endow the condensates with new functions.</p>","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076313","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}