Accounts of Chemical Research最新文献

{"title":"Oriented Electric Fields─Universal Catalysts","authors":"Sason Shaik*, , , David Danovich, , , Surajit Kalita, , and , Kshatresh D. Dubey*, ","doi":"10.1021/acs.accounts.5c00508","DOIUrl":"10.1021/acs.accounts.5c00508","url":null,"abstract":"<p >This Account outlines principles of electric-field-mediated chemistry, whereby oriented-external electric fields (OEEFs) function as universal “reagents” that control reactivity/selectivity and structures of molecules/clusters. The TOC graphics illustrate the rate-enhancing OEEFs for two different reactions. For the Diels–Alder reaction, we also mark the corresponding reaction-axis (<b>RA</b>). The <b>RA</b> arrow specifies the <b>directional-flow, of the electron density and bond-coupling</b>, from reactants to products (<b>RC</b>→<b>PC</b>). Determining the <b>RA</b> direction, for a given process, involves curly arrow-pushing in the charge-transfer direction. By convention, the arrowhead of the <b>RA signifies the direction of the negative charge flow</b> (Scheme 2). The arrowhead of the <i><b>F</b></i><sub><b>Z</b></sub> (OEEF) vector is marked as positive, hence corroborating the direction of negative charge flow, which will be induced by <i><b>F</b></i><sub><b>Z</b></sub>.</p><p >Thus, as the Account demonstrates, <i>the impact of OEEFs on reactions and structural transformations is unique</i>. <b>Energy-barriers-lowering generally occurs along a single direction in space</b>, specified by the <b>RA</b>. Furthermore, <b>the OEEF also catalyzes reactions in the presence of solvents</b>! For example, the computed OEEF lowers the barrier of the Menshutkin reaction (pyridine/CH<sub>3</sub>–I) by 10.6–12.6 kcal/mol in the three polar solvents. Thus, <b>solvent screening of the OEEF is imperfect</b> <i>(see F</i><sub><i>solvent-induced</i></sub> <i>in the conspectus art)</i>, and hence, chemical reactions are not limited to gas- or solid-phases. As the main text elaborates, <b>this imperfect screening-effect in solution is fundamental</b>, and applicable to reactions and to OEEF-induced structural changes. <b>As such, the OEEF is a universal enhancer of chemical change</b>.</p><p >The Account starts with conceptual principles for understanding and predicting the theoretically computed and/or experimentally observed OEEF effects on chemical reactions as well as structural transformations. These principles highlight the role of OEEFs as <b>tweezers</b> <i><b>that orient molecular species</b></i> <b>along the respective RAs</b>, and accelerate their transformation to products.</p><p >Subsequently, the paper describes experimental support of the theoretical results and guidelines. <b>Some of the applications also use continuous-flow setups, which</b> <i><b>will eventually scale-up product yields to Molar concentrations</b></i>, and render <i>OEEFs as practical tools in chemistry</i>. Evidence is presented for the potential existence of <b>OEEF/thermal dichotomy</b>, wherein <b>the OEEF-induced products differ from those which are produced corresponding thermal-only reactions</b> (see later work by Matile et al.).</p><p >The paper addresses also an important structural process; on the type of EEF (oscillating vs static), which carries out most ef","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3071–3080"},"PeriodicalIF":17.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147038","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":"Advances in Proximity-Assisted Bioconjugation","authors":"Mary Canzano,  and , Gonçalo J. L. Bernardes*, ","doi":"10.1021/acs.accounts.5c00368","DOIUrl":"10.1021/acs.accounts.5c00368","url":null,"abstract":"<p >Proximity-induced chemistry (PIC) refers to the transient reactivity between two or more molecules upon physical closeness which are otherwise unreactive. Harnessed by nature to control fundamental biological processes such as transcription and signal transduction, PIC increases the probability of correctly oriented, effective collisions, facilitating fundamental cellular processes. Within the field of chemical biology, PIC has been employed for several clinically relevant purposes, including the degradation of aberrant biomolecules and construction of protein therapeutics. This Account focuses on the application of PIC strategies for the development of site-specific bioconjugation techniques, termed proximity-assisted bioconjugation (PAB). Site-specific bioconjugation refers to the precise modification of biomolecules to generate homogeneous products. Such techniques are vital for the development of protein therapeutics including antibody–drug conjugates (ADCs), the investigation of the biological mechanisms of post-translational modifications (PTMs), and the visualization of biomolecular interactions <i>in vitro</i> and <i>in vivo</i>. While numerous strategies have been developed, many suffer from poor yields, limited product stability, demanding experimental procedures, and/or a lack of regioselectivity. Thus, PIC principles have been implemented to address these limitations, leading to the development of PAB strategies which achieve precise, regioselective modification of biomolecules. In this Account, we describe the development of PAB techniques within our group at the University of Cambridge and Instituto de Medicina Molecular (iMM) over the past five years. Our journey with PAB began serendipitously while investigating maleic acid derivatives for cysteine bioconjugation. Here, we discovered the secondary participation of proximal lysines on Trastuzumab-V205C and Gemtuzumab-V205C, conjugatable THIOMAB antibodies commonly used in ADCs, leading to the formation of distinct bioconjugate products relative to IgGs without such lysines. Further investigation into the proximal lysine (K207) of Trastuzumab-V205C revealed that residue 207 could be harnessed directly or mutated to precisely tune the stability of ADCs due to proximity interactions between K207 and covalent modifications of C205. Considering that two Trastuzumab drug conjugates are approved for clinical use, these findings have contributed to the evolving understanding of the chemical landscape of this antibody and help inform future ADC design and development. Further, we describe efforts from our group to develop two distinct PAB approaches: regioselective lysine acetylation of histone H3 and phage display-compatible peptide cyclization. These strategies combine induced-proximity with traditional bioconjugation techniques to enable regioselective modification of biomolecules which are historically difficult to selectively modify. These methods are readily adaptable to related s","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"2939–2955"},"PeriodicalIF":17.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141062","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":"Triplet–Triplet Annihilation Upconversion: From Molecules to Materials","authors":"Hong-Juan Feng, Ming-Yu Zhang, Lin-Han Jiang, Ling Huang, Dai-Wen Pang","doi":"10.1021/acs.accounts.5c00403","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00403","url":null,"abstract":"Photon upconversion, particularly triplet–triplet annihilation upconversion (TTA-UC), converts low-energy photons into higher-energy ones through multiphoton fusion, offering unique photophysical properties with broad applications. As a new generation of organic upconversion materials, TTA-UC shows great promise in biosensing, biomedicine, photoredox catalysis, and solar energy harvesting. For example, TTA-UC-based nanoprobes enable highly sensitive, background-free biomarker detection; TTA-UC nanoparticles act as phototransducers that extend optogenetic responses into the near-infrared region; their nonlinear luminescence supports high-resolution 3D printing; and they enhance photon utilization in photovoltaics. Although significant progress has been made in the past decade, challenges remain, including developing high-performance near-infrared TTA-UC pairs with ultralarge anti-Stokes shifts, creating general strategies for synthesizing water-dispersible and oxygen-resistant nanoparticles, and expanding biomedical applications to promote clinical translation.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"80 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077929","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":"Surface Manipulation in Cu- and Ag-Based Pre-Columbian Artifacts","authors":"Gabriel Maria Ingo*,&nbsp;, ,&nbsp;Cristina Riccucci,&nbsp;, ,&nbsp;Francesca Boccaccini,&nbsp;, ,&nbsp;Marianna Pascucci,&nbsp;, ,&nbsp;Elena Messina,&nbsp;, and ,&nbsp;Gabriella Di Carlo,&nbsp;","doi":"10.1021/acs.accounts.5c00415","DOIUrl":"10.1021/acs.accounts.5c00415","url":null,"abstract":"<p >Numerous metal artifacts of exceptional historical and artistic value from the Moche civilization (ca. 450 AD) were unearthed in the tomb of the Lady of Cao (El Brujo, Peru). The tomb yielded the tattooed, mummified remains of a young woman, who was approximately 25 years old at the time of her demise. The rich array of artifacts and insignia of power found within the tomb provides compelling evidence of her elevated status in the hierarchical Moche society. Among the artifacts, the gilded objects and intriguing apparently bimetallic nose ornaments, featuring adjacent gold and silver surfaces, are particularly noteworthy. These artifacts reveal the sophisticated craftsmanship of Moche metalworkers, who expertly produced and worked on Cu- and Ag-based alloys. Moche metalworkers, once they worked and shaped the alloys to a thickness of approximately 100–150 μm, in some artifacts meticulously formed localized, uniform, and thin (roughly 3–5 μm thick) gold- and silver-enriched surface layers by employing etching agents. This process involved the selective depletion of copper from Cu-based alloys and, in some regions, the removal of both copper and silver from a Ag–Cu–Au ternary alloy. The presence of epitaxially grown micrometric silver wires, which resemble the elongated architecture of naturally occurring silver curls, supports the hypothesis of a subtractive surface treatment. These findings demonstrate a pioneering, though empirical, capacity to produce specific Cu- and Ag-based alloys and to select suitable materials for surface manipulation. This capability led to the tailored chemical modification of the outermost layers, resulting in a fascinating monometallic or bimetallic appearance likely imbued with religious, symbolic, or shamanic values. It is noteworthy that the creation of such enthralling artistic masterpieces was uniquely enabled by this ability to manipulate matter at the micro- and nanoscale, combined with the goldsmiths’ artistic creativity.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"2997–3009"},"PeriodicalIF":17.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072434","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":"Catalytic Upcycling of PET: From Waste to Chemicals and Degradable Polymers","authors":"Zhenbo Guo,&nbsp;, ,&nbsp;Yuchen Li,&nbsp;, ,&nbsp;Meng Wang*,&nbsp;, and ,&nbsp;Ding Ma*,&nbsp;","doi":"10.1021/acs.accounts.5c00493","DOIUrl":"10.1021/acs.accounts.5c00493","url":null,"abstract":"<p >The global plastic waste crisis, driven by exponential growth in plastic production, has necessitated the development of innovative approaches for recycling and upcycling. Poly(ethylene terephthalate) (PET), one of the most widely used polyesters, poses significant environmental challenges due to its chemical stability and non-degradable nature. While existing methodologies have made significant contributions to the recycling of PET waste through mechanical or chemical processes, an emerging strategy of upcycling PET into high-value products may offer greater potential to present significant advantages in economic feasibility and long-term sustainability. Over the past ten years, hundreds of publications have explored the upcycling of PET in the laboratory through catalytic reactions with various co-reactants, primarily water, hydroxides, alcohols, and amines. In this Account, we summarize our contributions on the design of novel catalytic strategies for the upcycling of PET along with other problematic wastes and H₂. For instance, we explored the co-upcycling of PET with other plastics such as poly(vinyl chloride) (PVC) and polyoxymethylene (POM), demonstrating how the chlorine from PVC could be utilized to depolymerize PET into terephthalic acid (TPA) and 1,2-dichloroethane (EDC) and how the formaldehyde derived from POM could be converted into 1,3-dioxolane through the condensation reaction with ethylene glycol (EG) derived from PET. We also developed a one-pot catalytic system that simultaneously hydrogenated PET and CO₂ into high-value chemicals, leveraging a dual-promotion effect on both CO₂ hydrogenation and PET methanolysis and achieving high yields of EG, dimethyl cyclohexanedicarboxylate (DMCD) and <i>p</i>-xylene (PX). A H₂-free, one-pot, two-step catalytic process was further presented to upcycle PET with CO₂, yielding formic acid (FA) and TPA. Moreover, we demonstrated a direct hydrogenation strategy to convert PET into a degradable polyester, poly(ethylene terephthalate)–poly(ethylene-1,4-cyclohexanedicarboxylate) (PET–PECHD), through controlled hydrogenation of its aromatic rings, which preserved the polymer’s mechanical and thermal properties while introducing degradability, offering a sustainable alternative for packaging materials.</p><p >Our research highlights the importance of catalyst design, reaction engineering, and process optimization in achieving efficient and scalable PET upcycling processes. By integrating multiple catalytic steps and leveraging waste-derived resources, we outline a roadmap for the near future of PET upcycling, aiming to enable breakthroughs in real-life plastic upcycling.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 20","pages":"3184–3194"},"PeriodicalIF":17.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068508","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":"CO2 Chemical Fixation into Value-Added Heterocycles Catalyzed by Non-Noble-Metal Metal-Organic Frameworks","authors":"Fang-Yu Ren,&nbsp; and ,&nbsp;Bin Zhao*,&nbsp;","doi":"10.1021/acs.accounts.5c00482","DOIUrl":"10.1021/acs.accounts.5c00482","url":null,"abstract":"&lt;p &gt;The conversion of CO&lt;sub&gt;2&lt;/sub&gt; into high-value-added chemicals represents an effective strategy for CO&lt;sub&gt;2&lt;/sub&gt; utilization. However, due to the inherent thermodynamic stability of CO&lt;sub&gt;2&lt;/sub&gt;, its conversion primarily relies on harsh conditions, such as high temperatures and pressures, along with the involvement of noble-metal catalysts. The effective transformation of CO&lt;sub&gt;2&lt;/sub&gt; under mild conditions remains a significant challenge. Therefore, the development of efficient catalysts is of critical importance. Metal–organic frameworks (MOFs) are a class of porous crystalline materials formed by the self-assembly of metal ions with multidentate organic ligands through coordination bonds. Its precise and customizable structure, combined with high surface area and the ease of functional modification, makes it an ideal platform for catalytic applications. These advantages facilitate the design of catalysts with high activity, selectivity, and stability through rational structural modulation, significantly enhancing CO&lt;sub&gt;2&lt;/sub&gt; conversion into value-added products under mild conditions. Moreover, this enables a deep understanding of the relationship between catalyst structure and performance. Therefore, summarizing research in this field and providing in-depth insight into the application of MOF-based catalysts for CO&lt;sub&gt;2&lt;/sub&gt; conversion is crucial for advancing future developments.&lt;/p&gt;&lt;p &gt;In this Account, we will summarize and discuss recent advances on the structural design of non-noble metal MOFs and the mechanics in the catalytic conversion of CO&lt;sub&gt;2&lt;/sub&gt;, especially emphasizing how to enhance the catalytic activity and selectivity by modulating Lewis acid and/or base sites. This Account begins by outlining the challenges associated with CO&lt;sub&gt;2&lt;/sub&gt; conversion. Subsequently, illustrating why MOFs are promising catalysts for CO&lt;sub&gt;2&lt;/sub&gt; utilization. Next, we present several specific strategies for constructing highly efficient MOF-based catalysts utilized in CO&lt;sub&gt;2&lt;/sub&gt; conversion: (1) To overcome the stability challenges associated with MOFs in CO&lt;sub&gt;2&lt;/sub&gt; conversion, we designed and synthesized a series of cluster-based MOFs. The high connectivity of the metal clusters imparts exceptional structural stability. (2) We highlighted a new strategy involving multiple Lewis acid sites to synergistically catalyze the highly efficient conversion of CO&lt;sub&gt;2&lt;/sub&gt; under mild conditions without the need for noble metals. (3) To obtain selective conversion of different reactions, we simultaneously introduced both Lewis acid and Lewis base active sites into the MOF structure. This approach significantly enhances catalytic efficiency while enabling a “switch-on/off” effect for different CO&lt;sub&gt;2&lt;/sub&gt; reactions. (4) Through the nanoconfinement effect, we achieved substrate size selectivity and reaction pathway modulation, significantly improving the efficiency of multicomponent CO&lt;sub&gt;2&lt;/sub&gt; reactions and reducing the for","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3033–3045"},"PeriodicalIF":17.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068506","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":"Developing New Strategies to Construct Pseudo-natural Macrocycles for Undruggable Targets","authors":"Han Wang,&nbsp;, ,&nbsp;Tongyu Bi,&nbsp;, and ,&nbsp;Weibo Yang*,&nbsp;","doi":"10.1021/acs.accounts.5c00524","DOIUrl":"10.1021/acs.accounts.5c00524","url":null,"abstract":"&lt;p &gt;Up to 85% of human-disease-related target proteins are classified as undruggable. These targets play critical roles in disease pathogenesis and progression yet lack effective agents for therapeutic intervention. In recent years, strategies such as proteolysis-targeting chimeras (PROTACs) and molecular glues have emerged to modulate these undruggable targets, demonstrating considerable promise. Notably, macrocyclic compounds used for molecular glues have exhibited exceptional performance. They comprise ring structures typically formed by 12 or more atoms, representing a unique class of three-dimensional molecular architectures that balance conformational flexibility with structural rigidity. Studies indicate that macrocyclization strategies enhance target selectivity, improve binding affinity, and optimize drug-like characteristics of therapeutic candidates. Despite these advances, current macrocyclic drugs predominantly derive from natural products (NPs). Naturally occurring macrocycles often possess structural complexity, are isolated in low yields, and present significant synthetic challenges, thereby limiting their availability for clinical applications. Consequently, the development of innovative methodologies to construct pseudo-natural macrocycles capable of modulating undruggable targets holds substantial scientific and therapeutic importance─yet remains a formidable challenge.&lt;/p&gt;&lt;p &gt;Over the past five years, our group has established a modular biomimetic assembly strategy enabling the rapid generation of diverse pseudo-natural macrocycles exhibiting broad bioactivities. Our macrocycle design principle rests on three key tenets: (I) deconstructing natural product biosynthetic logic into programmable building blocks; (II) developing novel reactions to mimic natural bioactive building blocks; and (III) strategically replacing intricate chiral motifs with readily available amino acid derivatives. This paradigm has facilitated the rapid generation of pseudo-natural macrocycles with significant unexplored biological potential. In this Account, we highlight recent progress made in our group toward development of a modular biomimetic strategy and novel macrocyclization reactions to construct a pseudo-natural macrocycles library for modulating undruggable targets. Specifically, we categorize our work into four parts, including construction of a pseudo-natural macrocycles library, macrocyclic oxime modulating Hemagglutinin (HA) for anti-influenza A H1N1, spiro-fused macrocycles targeting silent information regulator (SIRT3) for treating Parkinson’s disease, and macrocycles targeting protein–protein interaction (PPI) for overcoming multidrug resistance (MDR). We highlight that structurally diverse, multifunctional bioactive pseudo-natural macrocycles can be produced concisely and sustainably. We hope that this Account delineated herein will broaden the application of this strategy and inspire the design of a variety of pseudo-natural macrocycle","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3096–3110"},"PeriodicalIF":17.7,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059030","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":"N-Acylamino Acid Amidothiourea: A Versatile Chiral Helical Building Block","authors":"Qian Wang,&nbsp;, ,&nbsp;Si-Yi Liu,&nbsp;, and ,&nbsp;Yun-Bao Jiang*,&nbsp;","doi":"10.1021/acs.accounts.5c00490","DOIUrl":"10.1021/acs.accounts.5c00490","url":null,"abstract":"<p >Thioureas represent an important class of molecular frameworks, distinguished by their hydrogen-bonding capabilities. This feature has enabled the development of a variety of synthetic anion receptors and advanced molecular technologies with applications in analysis, catalysis, and therapeutics. Over the past three decades, our lab has focused on establishing <i>N</i>-acylamino acid amidothiourea platforms to revolutionize the thiourea-based supramolecular functionality, particularly in anion recognition, chirality transfer, spontaneous resolution, and macrocyclization synthesis. This Account highlights representative studies from our lab and describes our exploration of the relationship between <i>N</i>-acylamino acid amidothiourea conformation, folding, and emerging material properties.</p><p >The design of thiourea-based anion receptors usually involves enhancing the hydrogen-bonding propensity of the thioureido −NH proton(s). Conventional strategies employ electron-withdrawing groups to increase the acidity of −NH(s), although this risks deprotonation of −NH when they are too acidic or encounter highly basic anions. Our lab developed an alternative strategy for this goal that circumvents this limitation. By incorporating electron-donating amide groups to generate <i>N</i>-amidothioureas and exploiting molecular allostery to drive intramolecular charge transfer (ICT), we achieved a dramatic enhancement in anion binding affinity by orders of magnitude. The <i>N</i>-amidothioureas also serve as dynamic regulators of intramolecular chirality transfer via N–N bond conformational switching from twisted to planar states. Notably, <i>N</i>-acylamino acid amidothioureas exhibit a pronounced template effect due to the folded β-turn structure, enabling efficient macrocyclization syntheses that were previously unattainable. This breakthrough has facilitated the construction of macrocycle-based nanopores for transmembrane transport. Furthermore, by integrating intermolecular binding sites, we achieved helicity propagation of the helical β-turn structure through self-assembly, yielding supramolecular double helices with a linear CD-<i>ee</i> dependence. It presents a critical step toward spontaneous resolution for practical applications.</p><p >Given the expanding interest in thiourea and its derivatives, our chiral helical building blocks provide a versatile platform for advancing functional thiourea-based materials.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3046–3059"},"PeriodicalIF":17.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043599","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":"Two-Dimensional Electrically Conductive Metal–Organic Frameworks: Insights and Guidelines from Theory","authors":"Shogo Nakaza,&nbsp;, ,&nbsp;Yuliang Shi,&nbsp;, ,&nbsp;Zeyu Zhang,&nbsp;, ,&nbsp;Shahid Akbar,&nbsp;, and ,&nbsp;Farnaz A. Shakib*,&nbsp;","doi":"10.1021/acs.accounts.5c00438","DOIUrl":"10.1021/acs.accounts.5c00438","url":null,"abstract":"&lt;p &gt;Two-dimensional (2D) metal–organic frameworks (MOFs) are a new class of multifunctional low-dimensional materials where extended layers of tetra-coordinated metal nodes with electron-rich π-conjugated organic linkers are stacked via van der Waals interactions. With two possible electron transport pathways along the intra- and interlayer directions, many 2D MOFs offer electrical conductivity on top of other known properties of MOFs, which include permanent porosity and exceptionally high surface area, promising unprecedented breakthroughs in producing high-performance and cost-effective materials for batteries, semiconductors, and supercapacitors. To make progress toward these applications, theoretical and computational tools play an essential role in unraveling structure–property–function relationships, identifying materials with tailored electronic properties, and developing design criteria for novel electrically conductive (EC) MOFs yet to be experimentally synthesized and characterized. However, such studies are still in their infancy, hampered by various factors including the high computational cost of simulating these complex extended materials composed of hundreds of atoms.&lt;/p&gt;&lt;p &gt;In this Account, we summarize and discuss our group’s efforts in mapping out the structure–property–function relationships of EC MOFs while deliberating present and future research on big data analysis and machine learning (ML) for novel materials discovery. First, selected examples of these electrically conductive materials will be discussed. We will present quantum mechanical calculations deciphering their thermodynamic stability, electronic structure, and photochemical reactivity. Second, to help the community move beyond selected studies of these materials, we introduce our EC-MOF Database. It is the only database solely dedicated to EC MOFs, which provides not only the crystal structures but also the electronic properties of 1057 structures calculated at the periodic density functional theory (DFT) level. We then discuss the application of ML techniques to utilize the EC-MOF Database in property predictions in a high-throughput manner. Lastly, we will introduce the flexible nature of these layered materials and discuss how it affects the nature of their electrical conductivity. Selected examples will be discussed to demonstrate the applicability and appropriateness of molecular dynamics (MD) simulations based on high-dimensional neural network potentials (NNPs) compared to the expensive &lt;i&gt;ab initio&lt;/i&gt; MD (AIMD) data.&lt;/p&gt;&lt;p &gt;The overarching objective of this Account is to bring to attention the computationally-ready crystal structures and the developed ML models and NNPs for EC MOFs so that the broader community can utilize them for further studies. This will also help experimental groups make informed decisions on designing and synthesizing novel EC MOF-based materials. With the possibility of inverse design based on the provided theoretical insig","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3021–3032"},"PeriodicalIF":17.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051310","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":"Molecular Glass from Solution Self-Assembly","authors":"Fei Nie,&nbsp; and ,&nbsp;Dongpeng Yan*,&nbsp;","doi":"10.1021/acs.accounts.5c00425","DOIUrl":"10.1021/acs.accounts.5c00425","url":null,"abstract":"&lt;p &gt;Glass is a vital material across diverse fields including photovoltaics, construction, medicine, telecommunications, and display technologies. Beyond conventional inorganic, metallic, and polymeric glasses, recent developments have introduced new families, such as supramolecular glasses (SGs), which exhibit greater structural diversity, molecular tunability, and functional versatility. Formed through noncovalent interactions, SGs allow for the incorporation of a wide range of molecular components and architectures.&lt;/p&gt;&lt;p &gt;However, SG fabrication remains largely dependent on melt-quenching, a method that demands high temperatures, costly equipment, and complex procedures. Additionally, thermal decomposition of many components prior to melting limits the design space for new SGs. These constraints highlight the need for alternative low-temperature synthesis methods. To address this challenge, our group recently introduced a sustainable and bottom-up approach based on metal–histidine complexes, termed evaporation-induced self-assembly (EISA). This solution-based technique enables the efficient production of various SGs, including single- and multicomponent organic glasses and organic–inorganic hybrids.&lt;/p&gt;&lt;p &gt;In the EISA process, molecular precursors are first dissolved in a solvent to form a uniform solution. Controlled solvent evaporation─under ambient pressure and moderate temperatures─increases viscosity, impeding the orderly organization of monomers. Simultaneously, polymerization progresses, leading to vitrification and glass formation. This low-energy, equipment-free process eliminates the need for thermal treatment or postprocessing and allows for solution-based recycling, aligning with principles of green chemistry and sustainable materials development.&lt;/p&gt;&lt;p &gt;Compared with inorganic and metallic glasses, solution-processed SGs offer several key advantages, including low density, high transparency, recyclability, and superior processability. Their properties can be tailored through the incorporation of functional moieties, such as dye molecules or metal ions, enabling tunable photoluminescence. The rigid SG matrix effectively restricts molecular vibrations, resulting in ultralong room-temperature phosphorescence (RTP), while the addition of chiral components can generate circularly polarized luminescence (CPL).&lt;/p&gt;&lt;p &gt;SGs fabricated via EISA exhibit multifunctionality, making them suitable for a wide range of applications. Their intrinsic ability to self-assemble into varied morphologies is ideal for the fabrication of advanced optical elements. The high viscosity of precursor solutions during evaporation facilitates their use as transparent adhesives. Additionally, their prolonged RTP performance also makes them attractive for anticounterfeiting and information security technologies.&lt;/p&gt;&lt;p &gt;The continued development of solution-assembled SGs will depend on several critical advances: scalable manufacturing methods, the integration of s","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3010–3020"},"PeriodicalIF":17.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051369","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}