Accounts of Chemical Research最新文献

{"title":"Photomechanical B←N Molecular Crystals: From Single-Crystal-to-Single-Crystal [2 + 2] Photodimerization to Polymerization","authors":"Subhrajyoti Bhandary*, Rahul Shukla, Anna M. Kaczmarek and Kristof Van Hecke*, ","doi":"10.1021/acs.accounts.5c00407","DOIUrl":"10.1021/acs.accounts.5c00407","url":null,"abstract":"<p >Organoboron-based crystalline compounds, which can respond to external stimuli (heat, light, electric field, or pressure), have already emerged as smart materials with well-directed functions. While various weak noncovalent interactions remain key to the supramolecular design, the exploitation of relatively strong boron–nitrogen dative bonds (B←N bonds) in constructing functional crystalline molecular and polymeric assemblies has recently attracted significant research interest. In particular, the strategic incorporation of B←N bonds into stimuli-responsive crystalline materials is promptly shaping a new direction in the field.</p><p >Photomechanical or photodynamic crystals are a special kind of stimuli-sensitive smart material that can undergo rapid dynamic motions (jumping, bending, splitting, or curling) when exposed to UV/visible light. These instantaneous macroscopic crystal movements promoted by the used light source are collectively known as “photosalient effects”. Metal-free/organic molecular crystals, exhibiting photosalient effects, provide an efficient choice of material to transform photon energy into mechanical work owing to their inherent lightweight, noncovalently bonded, and defectless packing. Therefore, such dynamic crystals are extremely relevant as an alternative to sustainable and flexible materials for soft robotics, actuators, energy storage, and sensors. These photodynamic crystal motions or photosalient effects can be induced by topochemical [2 + 2] cycloaddition reactions, mostly under high-energy UV light, as has recently been observed. In contrast, photodynamic motions triggered by visible light or even solar energy are less frequently encountered. However, topochemical [2 + 2] photoreactions do not always guarantee the exhibition of mechanical motions in crystals. While topochemical [2 + 2] photoreactivity has long been a subject of investigation, the study of photomechanical crystalline materials has only recently emerged as a key research focus.</p><p >Following the pioneering work of Schmidt (<contrib-group><span>Schmidt, G. M. J.</span></contrib-group> <cite><i>Pure Appl. Chem.</i></cite> <span>1971</span>, <em>27</em>, 647−678 <pub-id>10.1351/pac197127040647</pub-id>), the topochemical [2 + 2] photodimerization reaction of olefins has arisen as a promising route to obtain novel crystalline materials with a wide variety of topologies and unique properties based on small organic molecules, discrete metal complexes, metal-coordination polymers, and organic polymers, which are otherwise not achievable by solution-phase synthesis. When any topochemical transformation proceeds to “completion” in a single-crystal-to-single-crystal (SCSC) manner, it carries invaluable structural and mechanistic information related to the crystal properties. In all these compounds, weak supramolecular interactions (hydrogen/halogen/chalcogen bonds or stacking interactions) and robust metal-coordinate bonds have been observed to dire","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2724–2736"},"PeriodicalIF":17.7,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857656","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":"Applications of (l)-Acyclic Threoninol Nucleic Acids","authors":"Iben Caroline Stoltze,&nbsp; and ,&nbsp;Kurt Vesterager Gothelf*,&nbsp;","doi":"10.1021/acs.accounts.5c00288","DOIUrl":"10.1021/acs.accounts.5c00288","url":null,"abstract":"<p >The emerging class of (<span>l</span>)-<i>acyclic</i> threoninol nucleic acids ((<span>l</span>)-<i>a</i>TNAs) represents a novel type of xeno nucleic acids (XNAs), characterized by an acyclic nonribose backbone derived from the amino acid threonine. In this Account, the distinctive structural characteristics and broad spectrum of applications of (<span>l</span>)-<i>a</i>TNA are described. Compared to DNA and RNA, (<span>l</span>)-<i>a</i>TNA exhibits enhanced flexibility and conformational diversity. This flexibility, surprisingly, does not compromise but rather enhances the molecule’s stability in homoduplex formation, and it also forms stable heteroduplexes with both DNA and RNA. This unique structural configuration not only contributes to a remarkable resistance to nuclease degradation but also significantly extends its <i>in vivo</i> stability compared to natural nucleic acids, making (<span>l</span>)-<i>a</i>TNA a highly durable biomolecule for various applications.</p><p >One of the standout properties of (<span>l</span>)-<i>a</i>TNA is its ability to adopt a range of highly stable secondary structures, such as triplexes, G-quadruplexes, and i-motifs. This ability is maintained even under conditions such as low ionic strength, underscoring its potential utility in bioanalytical applications and therapy. The molecule’s versatility is further exemplified by its use in biotechnological applications, including toehold-mediated strand displacement reactions, which are important for constructing dynamic molecular systems that can respond to environmental cues with high specificity and stability. Moreover, (<span>l</span>)-<i>a</i>TNA’s capability to regulate gene expression through the formation of stable triplex structures presents promising potential for gene therapy, offering a method to control gene activity with precision. In the realm of drug delivery, the robustness of (<span>l</span>)-<i>a</i>TNA constructs, particularly in forming four-way junctions, underscores its efficacy under physiological conditions, highlighting its potential in creating drug delivery systems that exhibit minimal immune responses and no cytotoxicity. Additionally, the application of (<span>l</span>)-<i>a</i>TNA in nonenzymatic primer extension experiments provides crucial insights into the mechanisms of prebiotic chemistry and supports the pre-RNA world hypothesis. Recently, it was also demonstrated that the high stability of (<span>l</span>)-<i>a</i>TNA homoduplexes can be used in nucleic acid nanotechnology to assemble into ultrasmall 3D architectures with the potential for targeting and improved tissue penetration. The structural and chemical properties of (<span>l</span>)-<i>a</i>TNA, especially its enhanced thermal stability and resistance to enzymatic degradation, make it a promising tool in the fields of molecular biology, nanotechnology, and therapeutic development.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2671–2681"},"PeriodicalIF":17.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851198","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":"Ion Translocation Driven by Electric Field Generated in Excited-State Reactions","authors":"Hao-Ting Qu,&nbsp;Alexander P. Demchenko*,&nbsp;Igor O. Koshevoy* and Pi-Tai Chou*,&nbsp;","doi":"10.1021/acs.accounts.5c00434","DOIUrl":"10.1021/acs.accounts.5c00434","url":null,"abstract":"&lt;p &gt;The fundamental mechanism of ion translocation against the concentration gradient in biological systems has become a central focus of research. The variation of the electric field in response to external stimuli can be an essential trigger in this process. The introduction of molecular machines has enriched this field by providing a direct approach to converting energy into mechanical work. However, existing models mainly rely on photoisomerization dynamics that alter the location of ion-carrying molecular segments to achieve transportation. In a recent series of works, we present a new design of light-driven anion-translocating molecular machines that do not involve any conformational changes. In the designed structures, the dramatic redistribution of positive charge from the electron acceptor to the donor moiety in the dipolar cation dye is driven by excited-state intramolecular charge transfer (ESICT). This shifts the anion binding site to the opposite side of the molecule, facilitating a fast and directional ion motion. The continuous reversible cycle arises from the fact that the forward motion occurs during the excited-state lifetime on the high-energy potential energy surface, whereas the reverse reaction proceeds on the ground-state potential energy surface. Thus, the light quanta not only provide the energy source but also serve as the factor that drives the ion in the specified direction.&lt;/p&gt;&lt;p &gt;The unexpected observation about the anomalous dual-emission behavior of various phosphonium and pyridinium salts in nonpolar solvents has prompted the proposal of such a photoinduced counterion migration mechanism. Unlike the ultrafast ESICT process, which occurs on a subpicosecond time scale, the appearance of a strongly Stokes-shifted emission band─attributed to anion translocation─is observed over tens to hundreds of picoseconds. Furthermore, it was shown that the increase in ion radius results in the retardation of anion motion, which can be adequately explained by the mechanism we proposed. The interpretation of ion motion as a relaxation process toward electrostatic equilibrium is supported by the observed monoexponential decay of the spectral response function &lt;i&gt;C&lt;/i&gt;(&lt;i&gt;t&lt;/i&gt;) that is commonly used to describe the dynamics of solvent relaxations. Based on &lt;i&gt;C&lt;/i&gt;(&lt;i&gt;t&lt;/i&gt;) analysis, the dependence of the motion rate on the temperature and solvent viscosity demonstrated the absence of significant energy barriers during the process. Through structural modification of functional groups, the appended photoinduced intramolecular proton-transfer group anchored on the donor side enhances the efficiency of ion translocation.&lt;/p&gt;&lt;p &gt;In this Account, we briefly summarize recent reports on photoinduced counterion migration and highlight its potential for enabling transmembrane ion transport. Although challenges in future practical applications still need to be addressed, the core principle of modulating the directionality of anion migration ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2760–2769"},"PeriodicalIF":17.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843776","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":"Targeted Protein Acetylation Through Chemically Induced Proximity","authors":"Wesley W. Wang,&nbsp;Soumya Jyoti Singha Roy and Christopher G. Parker*,&nbsp;","doi":"10.1021/acs.accounts.5c00326","DOIUrl":"10.1021/acs.accounts.5c00326","url":null,"abstract":"<p >Protein acetylation is a pervasive and reversible post-translational modification (PTM) that impacts various protein features including stability, localization, and interactions and regulates diverse cellular functions, including transcription, signal transduction, and metabolism. This process is orchestrated by “writer” lysine acetyltransferases (KATs) and “eraser” deacetylases (KDACs), and its dysregulation is implicated in a broad spectrum of diseases including cancer, metabolic syndromes, and immune disorders. However, dissecting the roles of specific acetylation events in live cells remains a challenge due to the lack of tools that enable precise, rapid, and reversible acetylation at defined protein sites.</p><p >To begin addressing these challenges, we recently developed AceTAG (acetylation tagging), a chemically induced proximity (CIP) platform for targeted protein acetylation in live cells. AceTAG molecules are heterobifunctional ligands that recruit endogenous KATs─such as p300/CBP or PCAF/GCN5─to a tagged protein of interest, enabling selective, tunable, and dynamic acetylation. We demonstrated the utility of AceTAG across diverse proteins, including histone H3.3, p65/RelA, and p53. We further show that chemically induced acetylation of p53, including multiple hotspot p53 mutants, leads to enhanced stability and transcriptional activation, underscoring the potential of AceTAG for functional investigations and the potential for therapeutic exploration.</p><p >In this Account, we provide an overview of protein acetylation and survey chemical biology technologies for its manipulation, with a focus on AceTAG. We describe the conceptual motivation of AceTAG, applications, technical considerations, and recent efforts to expand this concept to endogenous proteins. Finally, we offer a forward-looking perspective of targeted acetylation as a chemical tool to investigate the biology of this PTM, as well as its potential as a therapeutic modality.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2695–2707"},"PeriodicalIF":17.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833438","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":"Activity-Based Fluorescent Probes for Reactive Sulfur Species","authors":"Ming Xian*,&nbsp;Yuqing Wang,&nbsp;Conrad Du and Meg Shieh,&nbsp;","doi":"10.1021/acs.accounts.5c00483","DOIUrl":"10.1021/acs.accounts.5c00483","url":null,"abstract":"<p >Reactive sulfur species (RSS), such as hydrogen sulfide (H₂S), hydrogen per/polysulfide (H₂S_<i>n</i>, <i>n</i> &gt; 1), hydropersulfides (RSSH), and polysulfides (RS_<i>n</i>R, <i>n</i> &gt; 2), are believed to play regulatory roles in redox biology. However, their exact mechanisms of action still need to be clarified. The instability of various RSS under physiological environments and their highly reactive natures pose unique challenges to the research on these species. Considering these challenges, fluorescent probes that can rapidly and specifically detect each individual RSS in biological settings are critical tools for RSS research. This Account follows our laboratory’s development of such probes.</p><p >We began by exploring the specific reactions of H₂S that could distinguish H₂S from other RSS. Based on the reactions, we developed several series of H₂S probes. We then investigated the reactions of other RSS, including H₂S_<i>n</i>, sulfane sulfur, HSNO, etc., and developed the corresponding probes. Our research on these probes also inspired us to develop other related chemical tools, including H₂S scavengers and a general structural template for xanthene-based near-infrared dyes. This Account summarizes our work in this field and systematically explains how each probe/chemical tool was designed and evaluated. This Account covers the following key points: (1) the rational chemical design of each probe template; (2) the evaluation and mechanistic insights for each probe template; and (3) the properties and applications of the probes/chemical tools.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2804–2814"},"PeriodicalIF":17.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819893","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":"An Acidic Cohydrolysis Route for the Hydrothermal Synthesis of Metal-Doping Zeolites","authors":"Xiaoling Liu,&nbsp;Yu Zhou* and Jun Wang*,&nbsp;","doi":"10.1021/acs.accounts.5c00256","DOIUrl":"10.1021/acs.accounts.5c00256","url":null,"abstract":"&lt;p &gt;Zeolites have been industrially applied in numerous chemical processes. Integrating metal species into zeolites to prepare metal-doping zeolites (Me-zeolites) is an efficient approach to modulating the redox/acid/base properties, porosity, and surface electronic state, strengthening the existing features and deriving extra functions. Direct hydrothermal synthesis of Me-zeolites is advantageous for integrating metal species throughout the whole zeolite matrix, enabling the metal species to have a versatile status and uniformly high dispersion. However, in the traditional alkaline hydrothermal route, most metal species tend to prematurely precipitate due to the mismatching of the hydrolysis/condensation rates between metal (rapid) and silica (slow) precursors, restricting the formation of Me-zeolites.&lt;/p&gt;&lt;p &gt;To address this issue, we develop a unique acidic cohydrolysis (ACH) route for direct hydrothermal synthesis of Me-zeolites: the metal and silica precursors are cohydrolyzed/condensed under a weakly acidic condition, which is then switched to an alkaline condition for gelation, and finally the resultant gel is hydrothermally crystallized into Me-zeolites. In this route, the initial weakly acidic environment slows down the hydrolysis rate of the metal precursor, matching that of the silica, during which the slowly hydrolyzed metal and silicon hydroxyls co-condense into Me–O–Si units. In the resulting alkaline gelation and final crystallization, the Me–O–Si units would resist the premature precipitation of metal species, allowing the smooth growth of the zeolite crystal to integrate the metal species into the zeolite matrix. Consequently, various kinds of Me-zeolites, namely, pristine zeolites, have been successfully synthesized through the ACH route.&lt;/p&gt;&lt;p &gt;In this Account, we describe the principle of the ACH route and summarize our persistent efforts in the synthesis, characterization, and application of Me-zeolites using this strategy. Different statuses of metal species including isomorphously substituted heteroatoms, metal oxides, and noble metal nanoparticles have thus been incorporated into zeolites with varied topologies and Si/Al ratios. Notably, the ACH route is applicable to engineering zeolite morphology on not only the microlevel but also the macrolevel. Enhanced performances of these ACH-synthesized Me-zeolites have been demonstrated in many heterogeneous catalysis processes, including biomass conversion, environmental catalysis, fine chemical and petrochemical syntheses, and shape-selective catalysis, as well as gas adsorption and separation, typically carbon capture. The robust zeolite framework-integrated metal sites that are synergistic with the regular micropore-derived confinement effect render an attractive prospect for Me-zeolites in new fields such as electrochemical and photothermal processes. The ACH route is now emerging as a promising alternative to greatly enriching the variety of Me-zeolites for innovative appli","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 16","pages":"2550–2561"},"PeriodicalIF":17.7,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797163","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 15","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":17.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/arv058i015_1966931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770414","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":"","authors":"Fei-Jian Chen,&nbsp; and ,&nbsp;Jihong Yu*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 15","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":17.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770420","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":"","authors":"Xi Wang,&nbsp;Yaakov Levy and Junji Iwahara*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 15","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":17.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770415","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":"","authors":"Weidi Cao,&nbsp;Xiaohua Liu* and Xiaoming Feng*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 15","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":17.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770407","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}