Accounts of Chemical Research最新文献

{"title":"Mainstream and Sidestream Modeling in Oxygen Evolution Electrocatalysis","authors":"Federico Calle-Vallejo*,&nbsp;","doi":"10.1021/acs.accounts.5c00439","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00439","url":null,"abstract":"<p >The oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are key in numerous electrochemical technologies, such as water electrolyzers, CO₂ electrolyzers, low-temperature fuel cells, regenerative fuel cells and some metal-air batteries. The OER and ORR tend to be sluggish and catalyzed by scarce and expensive materials, the durability of which is often insufficient. For two decades, computational methods have been regarded as a cost-effective means to explain experimental observations, test hypothesis, and design new materials for these two reactions.</p><p >Currently, the most widely used computational model is based on the free energies of the intermediates (*O, *OH, *OOH) and the scaling relations among them. Since the publication of two seminal papers in 2011, the scaling relation between the adsorption energies of *OOH and *OH was assigned all the responsibility for the experimental inefficiencies of OER and ORR electrocatalysts. This triggered a research paradigm based on breaking such scaling relation that still lasts until this day (see the diagram next to this text). After noting in 2018 that breaking the scaling relation between *OOH and *OH does not necessarily entail an improvement of the OER overpotential, my group moved away from the mainstream and has since been devising alternative descriptors and methods to enhance OER electrocatalysts and bifunctional OER/ORR electrocatalysts.</p><p >In this Account, I will describe when and why we introduced the concepts of electrochemical symmetry, delta-epsilon optimization, bifunctional volcano plot, and error awareness, among others, aiming to provide quantitative tools for the computational design and optimization of electrocatalysts.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2749–2759"},"PeriodicalIF":17.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924774","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":"Nanocatalytic Antioxidation: A General Chemical Approach for Alleviating Oxidative Stress in Diseases","authors":"Bowen Yang*,&nbsp; and ,&nbsp;Jianlin Shi*,&nbsp;","doi":"10.1021/acs.accounts.5c00408","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00408","url":null,"abstract":"&lt;p &gt;The overexpression of reactive oxygen species (ROS) is one of the major causes of various human diseases, including cardiovascular diseases, neurodegenerative diseases, and multiple inflammations, by initiating local oxidative stress at specific sites. The excessive ROS not only leads to oxidative injury of normal functional cells but also activates immune cells to aggravate inflammation. Therefore, scavenging excessive ROS is a feasible strategy for treating these diseases. Although many molecular drugs (such as &lt;i&gt;N&lt;/i&gt;-acetylcysteine and coenzyme Q10) have been approved for antioxidative therapies, from the perspective of chemical reaction, these antioxidant molecules can only act as reactants to react with ROS, leading to a nonsustainable antioxidative effect, largely compromising therapeutic outcome.&lt;/p&gt;&lt;p &gt;Our research team has proposed the concept of “nanocatalytic medicine”, which aims to use nanoparticles to trigger catalytic reactions in pathological sites, regulating the concentrations of ROS efficiently and sustainably for disease treatments. Till now, most efforts have been focusing on the development of pro-oxidative nanocatalysts to catalyze ROS generation for tumor therapy, which induces oxidative damage of cancer cells, while the antioxidative nanocatalysts for treating other oxidative stress-related diseases have been less reported, and the chemical strategy of nanocatalytic antioxidation has rarely been discussed specifically, which is in contrast to the conventional nanocatalytic pro-oxidation approach for tumor therapy.&lt;/p&gt;&lt;p &gt;During the last several years, our laboratory has developed various catalytic antioxidative nanosystems to trigger nanocatalytic antioxidation reactions for treating multiple diseases, including ischemic cardiomyopathy, diabetic cardiomyopathy, aortic dissection, alcoholic liver injury, inflammatory bowel disease, psoriasis, atopic dermatitis, rheumatoid arthritis, etc. From the perspective of chemical reaction, these nanosystems act as catalysts in antioxidation reactions and therefore will not be consumed but can lead to a sustainable and highly efficient antioxidative effect. Such a strategy not only largely elevates therapeutic efficacy but also reduces the doses of therapeutic agents required for administration. Moreover, the established catalytic antioxidation reactions may modulate the immune microenvironments at pathological sites, resulting in favorable therapeutic outcomes. In this Account, we will discuss the recent advances in our laboratory in the design and fabrication of antioxidative nanocatalysts for various disease treatments, highlighting nanocatalytic antioxidation as a general chemical strategy for alleviating oxidative stress in diseases. The material chemistry of these catalytic antioxidative nanosystems will be elucidated, which underlies elevated therapeutic outcome. It is expected that such a chemical strategy of nanocatalytic antioxidation will make a significant contri","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2708–2723"},"PeriodicalIF":17.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924775","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":"Late Metal Sandwich Catalysts for Olefin Polymerization","authors":"Joseph T. Medina,&nbsp;Quan H. Tran,&nbsp;Girish G. Ramachandru,&nbsp;Maurice Brookhart* and Olafs Daugulis*,&nbsp;","doi":"10.1021/acs.accounts.5c00440","DOIUrl":"10.1021/acs.accounts.5c00440","url":null,"abstract":"&lt;p &gt;Polyolefins are by far the most ubiquitous industrially produced polymers and are primarily produced by early transition metal catalysts. These catalysts are not functional group tolerant, and copolymerization of ethylene and polar vinyl monomers is quite challenging. Furthermore, early metal catalysts convert ethylene to linear polyethylene, and introduction of branches requires addition of comonomers. In this Account, we describe our efforts in designing and implementing new Pd(II) and Ni(II) olefin polymerization catalysts based on mechanistic understanding of the chain growth process. The original hindered nickel- and palladium-aryl-substituted diimine complexes were discovered in 1995. The key to the success of these now “classic” systems in generating high polymers rather than dimers or oligomers was realizing that incorporation of ortho-disubstituted aryl groups partially blocks the axial sites of the metal and thus retards the rate of chain transfer relative to propagation. Two key features of these late metal catalysts distinguish them from early metal complexes. First, they tolerate certain functional groups, which allows copolymerization of olefins with polar comonomers. Second, they can form a branched polymer from ethylene without the need to add α-olefin comonomers. Importantly, for nickel catalysts, branching levels can be modulated by changing reaction conditions, such as temperature and monomer pressure.&lt;/p&gt;&lt;p &gt;Based on molecular modeling, we speculated that 8-(arylnaphthyl) substitution in α-diimine catalysts should result in sandwich-type structures and thus exhibit much more efficient blocking of the axial sites relative to the classical ortho-disubstituted aryl diimines. This analysis proved to be quite fruitful. In this Account we describe the synthesis of palladium and nickel sandwich catalysts, mechanistic investigations of their catalytic behavior, and their use in building new polymer structures. The enhanced axial shielding by the two capping aryl groups in these catalysts results in exceptionally slow rates of chain transfer and, consequently, formation of extremely high molecular weight polymers with very narrow molecular weight distributions, features characteristic of living polymerizations. This behavior, coupled with the ability (particularly for nickel) to control polymer branching densities and thus mechanical properties through pressure and temperature variations permits generation of ultrahigh molecular weight polyethylenes (&lt;i&gt;M&lt;/i&gt;&lt;sub&gt;n&lt;/sub&gt;’s over 10&lt;sup&gt;7&lt;/sup&gt; Da) with branches ranging from 9 to 100 per 1000 carbons and &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;m&lt;/sub&gt; values from 17 to 132 °C. Furthermore, the living nature of the polymerization and the variation of branching with pressure has permitted the synthesis of diblock and multiblock polymers with narrow dispersities and complete control of molecular weights as well as specification of hard and soft segment lengths. Such structures are receiving extensive attention a","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2770–2780"},"PeriodicalIF":17.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870114","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":"Direct Optical Processing of Electrochromic Materials for Non-emissive Displays","authors":"Chang Gu,&nbsp;Guojian Yang,&nbsp;Sean Xiao-An Zhang and Yu-Mo Zhang*,&nbsp;","doi":"10.1021/acs.accounts.5c00433","DOIUrl":"10.1021/acs.accounts.5c00433","url":null,"abstract":"<p >The rapid evolution of human–machine interaction frameworks and global digitization initiatives has imposed heightened requirements for intelligent display systems. Electrochromic (EC) non-emissive displays, which dynamically modulate optical properties (e.g., color, absorption, transmittance) via electrochemically driven redox processes, represent a significant advancement in next-generation display architectures. These systems inherently have advantages including ultralow power consumption, sunlight-readable contrast, eye comfort, optical transparency, and mechanical flexibility. Nevertheless, their practical implementation remains constrained by undesirable spatial resolution and EC performances.</p><p >The direct optical processing strategy has emerged as a paradigm-shifting approach, facilitating photochemical modification of EC functional materials through noncontact photoirradiation protocols. This strategy demonstrates unparalleled capabilities in resolution control and scalable manufacturing throughput. Furthermore, on-demand precision engineering of EC materials via in situ photoactivated cross-linking, bond cleavage, and polymerization enables systematic optimization of electro-optical responsiveness and multidimensional functional integration. These features position direct optical processing as a foundational methodology for high-precision display fabrication, directly addressing EC resolution and performance bottlenecks.</p><p >In this Account, we present a comprehensive overview of our recent advances in direct optical processing protocols for EC material systems in non-emissive display applications. By correlating material structural characteristics with photochemical mechanisms, we analyze three systematic processing approaches: matrix-engineered lithography, covalent-engineered lithography, and surface-engineered lithography. Then we introduce corresponding single-pixel addressing capabilities based on passive or active matrix driving modes. The discussion subsequently evaluates the positive enhancement of EC performance in electro-optical modulation dynamics and durability enabled by direct optical processing while elucidating the mechanistic relationship between optical processing parameters and device functionality. Additionally, extended applications in ultra-fine displays, flexible wearable electronics, optical communications, and integrated multifunctional applications are outlined. This Account concludes with a forward-looking roadmap for commercialization, highlighting synergistic opportunities between EC material innovations and advanced direct optical processing platforms to accelerate the realization of EC non-emissive display technologies.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 17","pages":"2737–2748"},"PeriodicalIF":17.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881627","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":"Multi-Catalytic-Field Assisted Conversion of Low-Concentration CO₂ in Steel Byproduct Gas for Synergistic Steel-Chemical Production.","authors":"Qiannan Li, Guangsheng Wei, Jian Qi, Kun Zhao, Baochen Han","doi":"10.1021/acs.accounts.5c00348","DOIUrl":"10.1021/acs.accounts.5c00348","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusThe iron and steel industry, as a major global CO&lt;sub&gt;2&lt;/sub&gt; emitter, urgently requires technological breakthroughs in its carbon neutrality pathway. Existing emission reduction technologies such as carbon capture, utilization and storage are economically insufficient, while the full utilization of byproduct gas may lead to energy shortages in steel enterprises. Steel byproduct gases (e.g., converter gas) have complex composition, and traditional combustion results in high emissions. In this context, the proposed low concentration CO&lt;sub&gt;2&lt;/sub&gt; (LCC) system demonstrates dual advantages: (1) enhancing the calorific value of the byproduct gas to meet the demands of high-energy steelmaking processes and (2) achieving the recovery of high-purity CO&lt;sub&gt;2&lt;/sub&gt; postcombustion, thereby facilitating the carbon neutrality pathway with minimized separation energy consumption. However, components such as CO and N&lt;sub&gt;2&lt;/sub&gt; in the gas lead to competitive adsorption, low catalytic selectivity, and complex reaction pathways, necessitating breakthroughs in catalytic mechanisms and process innovation.This Account based on the research accumulation of the authors' team in the field of CO&lt;sub&gt;2&lt;/sub&gt; catalytic reduction and iron and steel metallurgy systematically reviews the key scientific issues and technological advancements in the catalytic conversion of LCC, using converter gas as a typical case. First, addressing the challenge of selective CO&lt;sub&gt;2&lt;/sub&gt; adsorption, the competitive mechanisms of different adsorption models in complex gas environments were explored. Second, in terms of activation and reaction pathway regulation, the influence patterns of gases such as CO and N&lt;sub&gt;2&lt;/sub&gt; on the CO&lt;sub&gt;2&lt;/sub&gt; reduction reaction are analyzed. Furthermore, through in-depth analysis, new principles and processes for CO&lt;sub&gt;2&lt;/sub&gt; adsorption in novel scenarios, catalyst matching, and directional design, material surface reconstruction under industrial environmental conditions is considered. Finally, we integrate the LCC reduction technology into the synergistic steel-chemical production technology route, focusing on elucidating the scientific design principles of meso-macro bridging in the engineering application process, providing a reference for the treatment of various industrial flue gases and tail gases.The LCC catalytic reduction technology aids steel industry carbon emission reduction through \"source conversion-end utilization\", but its industrialization requires collaborative innovation in theory and engineering. Future efforts should focus on the catalytic surface and interface mechanisms under complex gaseous conditions, develop highly efficient and stable catalysts, and design an integrated intelligent system of \"catalysis-calorific value-chemical\" to promote the near-zero carbon transformation in the steel industry. This technology not only supports carbon neutrality in the steel industry but also provides interdisciplinary solu","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":17.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870115","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":"Crystalline Porous Frameworks via Hierarchical Dynamic Covalent Assembly.","authors":"Yanqing Ge, Shaofeng Huang, Zhehao Yuan, Wei Zhang","doi":"10.1021/acs.accounts.5c00393","DOIUrl":"10.1021/acs.accounts.5c00393","url":null,"abstract":"<p><p>ConspectusCrystalline porous frameworks, such as covalent organic frameworks (COFs), metal-organic frameworks (MOFs), and hydrogen-bonded organic frameworks (HOFs), have demonstrated exceptional potential in diverse applications, including gas adsorption/separation, catalysis, sensing, electronic devices, etc. However, the building blocks for constructing ordered frameworks are typically limited to multisubstituted aromatic small molecules, and uncontrolled interpenetration has remained a long-standing challenge in the field. Shape-persistent macrocycles and molecular cages have garnered significant attention in supramolecular chemistry and materials science due to their unique structures and novel properties. Using such preporous shape-persistent 2D macrocycles or 3D cages as building blocks to construct extended networks is particularly appealing. This <i>macrocycle-to-framework/cage-to-framework</i> hierarchical assembly approach not only mitigates the issue of interpenetration but also enables the integration of diverse properties in an emergent fashion. Since our demonstration of the first organic cage framework (OCF) in 2011 and the first macrocycle-based ionic COFs (ICOFs) in 2015, substantial advancements have been made over the past decade. In this Account, we will summarize our contributions to the development of crystalline porous frameworks, consisting of shape-persistent macrocycles and molecular cages as preporous building blocks, via hierarchical dynamic covalent assembly. We will begin by reviewing representative design strategies and the synthesis of shape-persistent macrocycles and molecular cages from small molecule-based primary building blocks, emphasizing the critical role of dynamic covalent chemistry (DCvC). Next, we will discuss the further assembly of preporous macrocycle/cage-based secondary building blocks into extended frameworks, followed by an overview of their properties and applications. Finally, we will highlight the current challenges and future directions for this hierarchical assembly approach in the synthesis of crystalline porous frameworks. This Account offers valuable insights into the design and synthesis of functional porous frameworks, contributing to the advancement of this important field.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":17.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870113","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":"Photomechanical B←N Molecular Crystals: From Single-Crystal-to-Single-Crystal [2 + 2] Photodimerization to Polymerization","authors":"Subhrajyoti Bhandary*,&nbsp;Rahul Shukla,&nbsp;Anna M. Kaczmarek and Kristof Van Hecke*,&nbsp;","doi":"10.1021/acs.accounts.5c00407","DOIUrl":"10.1021/acs.accounts.5c00407","url":null,"abstract":"&lt;p &gt;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.&lt;/p&gt;&lt;p &gt;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.&lt;/p&gt;&lt;p &gt;Following the pioneering work of Schmidt (&lt;contrib-group&gt;&lt;span&gt;Schmidt, G. M. J.&lt;/span&gt;&lt;/contrib-group&gt; &lt;cite&gt;&lt;i&gt;Pure Appl. Chem.&lt;/i&gt;&lt;/cite&gt; &lt;span&gt;1971&lt;/span&gt;, &lt;em&gt;27&lt;/em&gt;, 647−678 &lt;pub-id&gt;10.1351/pac197127040647&lt;/pub-id&gt;), 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}