Accounts of Chemical Research最新文献

{"title":"Postsynthetic Modification of Metal-Organic Layers.","authors":"Zhiye Wang, Lingyun Cao, Huihui Hu, Cheng Wang","doi":"10.1021/acs.accounts.4c00726","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00726","url":null,"abstract":"<p><p>ConspectusMetal-organic layers (MOLs), as a subclass of two-dimensional (2D) metal-organic frameworks (MOFs), have gained prominence in materials science by combining the structural versatility of MOFs with the unique physical and chemical properties of 2D materials. MOLs consist of metal oxide clusters connected by organic ligands, forming periodically extended 2D architectures with tunable properties and large surface areas. These characteristics endow MOLs with significant potential for applications in catalysis, sensing, energy storage, and biomedicine.The synthesis of MOLs predominantly follows two key pathways: top-down exfoliation of bulk layered MOFs and bottom-up assembly from molecular building units. The exfoliation method allows for the isolation of ultrathin MOL sheets from bulk precursors, but scalability and structural defects present ongoing challenges. In contrast, the bottom-up assembly offers more precise control over structural design, enabling the formation of MOLs with tailored chemical functionalities and morphologies. By carefully selecting linkers and synthetic conditions, researchers have successfully constructed MOLs with diverse geometric configurations including linear, triangular, and rectangular ligand motifs. Nevertheless, achieving consistent monolayer formation and controlling lateral dimensions remain critical challenges for the widespread application of these materials.A defining advantage of MOLs is their exceptional amenability to postsynthetic modification (PSM). PSM strategies enable fine-tuning of MOL properties and the introduction of novel functionalities without compromising the integrity of the underlying framework. Four principal approaches to PSM have been established: (1) linker modification, where additional coordination sites facilitate selective metalation or functional group incorporation; (2) secondary building unit (SBU) modification, using replaceable sites perpendicular to the MOL plane for targeted functionalization; (3) dual modification, integrating linker and SBU functionalization to achieve complex multifunctional platforms; and (4) multilevel assembly, incorporating MOLs into larger hierarchical architectures such as biomimetic systems and composite materials.These versatile modification strategies have unlocked novel applications of MOLs, including single-site catalysis, photocatalysis, and artificial photosynthetic systems. For instance, MOLs functionalized with transition metal complexes have more accessible reactive sites than conventional MOFs for faster substrate transport. Additionally, MOLs interfaced with biomimetic systems, such as liposomes and proteins, have demonstrated significant promise in photochemical energy conversion and selective oxidation processes.Despite these advancements, several key obstacles persist. Achieving uniform monolayer thickness while preventing multilayer aggregation remains a formidable task, necessitating deeper insights into the thermodyna","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565523","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-Atom Deletion Involving Rearrangement of Sulfamoyl Azides or Triazanium Salts.","authors":"Bowei Huang, Hongjian Lu","doi":"10.1021/acs.accounts.4c00853","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00853","url":null,"abstract":"<p><p>ConspectusAmines are frequent structural components in natural products, pharmaceuticals, ligands, and catalysts, making their synthesis and transformation essential to organic chemistry. While C-N bond formation has become a well-established and reliable synthetic strategy, the selective cleavage of C-N bonds remains relatively underexplored. This challenge arises from the low heterolytic nucleofugality of nitrogen, a property that limits the practical application of C-N bond cleavage. This gap underscores a significant area in synthetic methodology in need of further development. In this context, N atom deletion─defined as the selective removal of a nitrogen atom <i>via</i> C-N bond cleavage, while preserving the integrity of the remaining framework─has emerged as a promising approach for skeletal editing. Since Levin's landmark 2021 report, N atom deletion has gained attention for its potential to precisely modify molecular skeletons. Building on the skeletal editing concepts advanced by Levin and Sarpong, particularly their strategies for modifying cyclic frameworks, we recognized the critical need for developing mild and efficient methods that enable the structural manipulation of cyclic systems.This Account summarizes our research since 2017, focusing on two approaches to N atom deletion with distinct mechanisms: the rearrangement of sulfamoyl azides and the conversion of triazanium intermediates. Initially, we explored and optimized the thermal rearrangement of sulfamoyl azides derived from secondary amines, discovering its potential as a viable synthetic strategy for N atom deletion. In 2024, we introduced an O-diphenylphosphinyl hydroxylamine (DPPH)-promoted N atom deletion, involving the generation and novel rearrangement of triazanium intermediates. Both methods enable the conversion of polar aliphatic amines into nonpolar scaffolds and are applicable to both linear molecules and cyclic systems of varying sizes. The DPPH-based approach, in particular, demonstrated exceptional effectiveness for sterically hindered substrates with mild reaction conditions and no need for anhydrous or oxygen-free environments. The mechanisms of two methods─both via isodiazene and radical intermediates─were elucidated through rigorous experimental investigation. Additionally, we observed the rapid formation of hydro(deutero)deamination products when primary amines were exposed to DPPH.Beyond its role as a typical skeletal editing strategy, N atom deletion of secondary amines has emerged as a crucial synthetic approach. Though with limitations, it transforms the challenging task of constructing C-C bonds into a more manageable sequence: the formation of C-N bonds following selective N atom removal. We have applied this strategy in the synthesis of natural products, ligands, hydrocarbon cages, and pharmaceuticals. We hope that this work will stimulate further interest in N atom deletion as a skeletal editing strategy and encourage its incorporation int","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571515","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":"Aldehyde-Stabilization Strategies for Building Biobased Consumer Products around Intact lignocellulosic Structures.","authors":"Shasha Zheng, Songlan Sun, Lorenz P Manker, Jeremy S Luterbacher","doi":"10.1021/acs.accounts.4c00819","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00819","url":null,"abstract":"<p><p>ConspectusDwindling fossil resources and their associated environmental concerns have increased interest in biobased products. In particular, many approaches to convert lignocellulosic biomass into small-molecule building blocks are being explored via thermal, chemical, and biological processes. Depending on their structure, these molecules can be used as direct (i.e., drop-in) or indirect (different molecule from what is used today) substitutes for petrochemicals. In all such cases, biomass must be deconstructed, which involves the depolymerization of lignin and polysaccharides as well as their further transformation to produce these substitutes. Deconstruction often requires harsh conditions that cause degradation, and further upgrading implies multiple conversion steps, especially for drop-in molecules, all of which lead to low atom economy. Our group has developed an aldehyde-stabilization strategy that facilitates the depolymerization of lignocellulose to monomers in high yields by stabilizing intermediates under biomass deconstruction conditions. This strategy has now been adapted to prepare indirect substitutes for petrochemicals with very high atom economy including biobased solvents, plastic precursors, adhesives, and surfactants, which have widespread applications in modern society.In this Account, we first introduce the function of aldehydes using formaldehyde (FA) as an example. Specifically, we discuss their role in assisting lignin isolation and their ability to stabilize lignin by looking at the lignin monomer yields that can be obtained after hydrogenolysis of the associated aldehyde-functionalized lignin. Highly selective production of lignin monomers was achieved using acetaldehyde (AA) or propionaldehyde (PPA) as a stabilization reagent via either reductive or oxidative depolymerization. In a typical FA-assisted fractionation, hemicellulose was directly converted into diformylxylose (DFX), while cellulose with properties similar to those obtained by organosolv was isolated but could be converted to diformyl-glucose isomers (DFGs) by further hydrolysis. These stable molecules provide us a new method to preserve sugar molecules that often degrade during acidic fractionation, which will be discussed in Section 3. Besides, DFX can also be used as a green solvent (Section 4), while FA-lignin exhibits excellent adhesion properties for plywood preparation (Section 5). Biobased glyoxylic acid (GA) was used to convert hemicellulose into a high yield of dimethylglyoxylic-acid-xylose (DMGX), a terephthalic acid (TA) substitute for bioplastics production (Section 6), while GA-lignin demonstrates great amphiphilic properties and finds applications as surfactants in cosmetic products (Section 7). When fatty aldehydes were used as stabilization reagents, both lignin and hemicellulose were converted to surfactants by downstream defunctionalization (Section 7). We will also discuss the current limitations of this aldehyde-stabilization st","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565517","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":"E. B. Hershberg Award: Taming Inflammation by Tuning Purinergic Signaling.","authors":"Kenneth A Jacobson","doi":"10.1021/acs.accounts.5c00011","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00011","url":null,"abstract":"<p><p>ConspectusThe author presents his personal story from early contributions in purinergic receptor research to present-day structure-guided medicinal chemistry. Modulating purinergic signaling (encompassing pyrimidine nucleotides as well) and other nucleoside targets with small molecules is fruitful for identifying new directions for therapeutic intervention. Purinergic signaling encompasses four adenosine receptors, eight P2Y receptors that respond to various extracellular nucleotides, and trimeric P2X receptors that respond mainly to ATP. Each organ and tissue in the body expresses some combination of this family of cell-surface receptors, along with the enzymes and transporters that form, degrade, and process the native nucleoside and nucleotide agonists. The purinergic signaling system responds to physiological stress to an organ, for example by increasing the energy supply or decreasing the energy demand. The receptors are widespread on immune cells, such that P2Y and P2X receptor activation boosts the immune response when and where it is needed, for example to repel infection. In contrast, the adenosine receptors, which are activated later in the process─as stress-elevated ATP is hydrolyzed locally to adenosine by ectonucleotidases─tend to put the brakes on inflammation and can be used to correct an imbalance in pro- versus anti-inflammatory signals, such as in chronic pain. Hypoxia activates the immunosuppressive extracellular adenosine-A<sub>2A</sub> adenosine receptor axis, as originally formulated by Sitkovsky, which suppresses the immune response in the tumor microenvironment to make a cancer more aggressive. Conversely, the anti-inflammatory effects of adenosine receptor agonists have numerous therapeutic applications. Modulators of P2Y receptors, which respond to extracellular nucleotides, also show promise for treating chronic pain, metabolic disorders, and inflammation. Thus, control of this signaling system can be harnessed for treating a wide range of conditions, from cancer and neurodegeneration to autoimmune inflammatory diseases to ischemia of the brain or heart.The author's receiving the American Chemical Society's top award for medicinal chemistry in 2023 provides an opportunity to summarize these developments from their origins in empirical probing of receptor-ligand structure-activity relationship (SAR) to the current structure-based approaches, including conformational control of selectivity toward purinergic signaling. The work on each target receptor began either before or soon after it was cloned, and the initial focus was an academic exercise to use organic chemistry to develop a SAR for each target. The Jacobson lab has introduced chemical probes for 17 of the purinergic receptors as well as for associated regulators. Furthermore, surprisingly, some of the conformationally constrained nucleoside analogues can be designed to inhibit non-purinergic targets selectively, such as opioid and serotonin receptors and mon","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565520","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":"Structural and Mechanistic Advances in the Chemistry of Methyl-Coenzyme M Reductase (MCR).","authors":"Bojana Ginovska, Simone Raugei, Stephen W Ragsdale, Christopher Ohmer, Ritimukta Sarangi","doi":"10.1021/acs.accounts.4c00730","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00730","url":null,"abstract":"<p><p>ConspectusMethane represents 34% of U.S. energy consumption and is a major greenhouse gas related to the global carbon cycle and energy production. However, current industrial practices significantly increase atmospheric methane levels, necessitating a deeper understanding of its biosynthesis and oxidation. Methyl-coenzyme M reductase (MCR) is central to biological methane metabolism, catalyzing the final step of methanogenesis and the first step in anaerobic methane oxidation. It is also a key target for strategies to capture and transform methane into value-added chemicals.The active site of MCR is a buried Ni-based cofactor only accessible by the substrates via a 50 Å long tunnel. Although the Ni(I) state is required to initiate catalysis, capturing this state remains a challenge for the current structural techniques. Recent advances in structural biology using X-ray Free-Electron Laser serial crystallography have provided insights into MCR's inactive Ni(II) state at room temperature and show promise for capturing its active Ni(I) form.Our team has established several critical aspects of the MCR mechanism using a combination of experimental and computational studies. MCR uses CH<sub>3</sub>-SCoM and CoBSH as substrates, producing methane and a disulfide product CoMSSCoB. Kinetic analysis showed that productive substrate binding requires CH<sub>3</sub>-SCoM to bind first, inducing conformational changes that optimize the active site for subsequent CoBSH binding. Following substrate binding, four proposed methane production/oxidation mechanisms were examined, establishing whether the reaction proceeds through an organometallic methyl-nickel(III), methyl anion ion, or methyl radical intermediate. Experimental measurements using CoBSH analogs successfully slowed the reaction, allowing for mechanistic insight that demonstrated the methyl radical pathway, where the initial interactions involve homolytic cleavage of the methyl-sulfur bond, generating a methyl radical that quickly abstracts the thiol hydrogen atom of CoBSH to form methane. Computational studies further confirmed that, compared to other mechanisms, the methyl radical mechanism is thermodynamically more favorable and accessible under physiological conditions.Spectroscopic and computational studies challenged the conventional understanding of substrate binding in MCR by proposing an alternative positioning of CH<sub>3</sub>-SCoM and CoMSSCoB in the active site pocket. The research suggested that CH<sub>3</sub>-SCoM (substrate) and CoMSSCoB (product) bind via their sulfonate groups to the Ni(I) center of cofactor F<sub>430</sub>. This binding allows for the reaction without substrate reorganization in the pocket but would require a long-range electron transfer.Overall, the work summarized in this review reflects our current understanding of the enzyme's catalytic mechanism and structural dynamics. This is essential for developing efficient methane conversion technologies that could ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555261","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":"Single-Electron-Transfer-Mediated Carbonylation Reactions.","authors":"Le-Cheng Wang, Xiao-Feng Wu","doi":"10.1021/acs.accounts.5c00039","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00039","url":null,"abstract":"<p><p>ConspectusTransition-metal-catalyzed carbonylation coupling methods have been accepted as an essential tool for producing carbonylated products over the past few decades. Despite its long-standing history and widespread industrial applications, several challenges remain in carbonylation chemistry. These include reliance on precious metal catalysts, the need of high-energy radiation, difficulties in carbonylation of unactivated chemical bonds, etc. As an alternative to classic two-electron transfer process, single-electron-transfer (SET)-mediated carbonylation has emerged as a powerful tool to achieve elusive carbonylation transformations. Over the past few years, carbonylation of commonly available functional handles, such as alkenes and alkyl halides, via the single-electron pathway has emerged as a valuable area of research.Our team has been dedicated to developing new carbonylation reactions using bulk chemicals to construct high-value carbonylated products. These reactions have broad synthetic and industrial applications, motivating us to explore SET-mediated carbonylation transformations for two key classes of bulk chemicals: alkanes and alkyl halides. Specifically, our work has centered on two main approaches: (1) Single-electron reduction of C(sp<sup>3</sup>)-X bonds: this strategy leverages single-electron reduction to activate C(sp<sup>3</sup>)-X bonds, promoting the formation of carbon radicals, which in turn promotes subsequent addition to metals or CO. However, a significant challenge lies in the highly negative reduction potential of certain substrates [E<sub>red</sub> < -2 V compared to the saturated calomel electrode (SCE) for unactivated alkyl iodides]. Despite these challenges, the intrinsic reducibility of CO and the reactivity of various carbonyl-metal intermediates facilitate smooth reaction progress. (2) Single-electron oxidative of C(sp<sup>3</sup>)-H bonds: this strategy emphasizes efficiency, high atomic utilization, and minimal waste by bypassing traditional preactivation methods. Using 3d metal catalysts, we have successfully performed aminocarbonylation and alkoxycarbonylation on a wide range of C(sp<sup>3</sup>)-H bonds (such as those in aliphatic alkanes, ethers, amines, etc.). The above two approaches also enabled radical relay carbonylation of alkenes, allowing precise control over reaction intermediates and pathways. Such control improves both reaction efficiency and selectivity. These advancements have enabled transition metal or photoredox catalysis to facilitate radical relay carbonylation of unactivated alkenes, resulting in transformations such as oxyalkylative carbonylation, aminoalkylative carbonylation, fluoroalkylative carbonylation, double carbonylation, and rearrangement carbonylation.SET-mediated carbonylation significantly enhances the sustainability and scalability of the carbonylation process by reducing reliance on precious metal catalysts and enabling milder reaction conditions. Additionally,","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555259","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":"Strengthening Liquid Crystal Elastomer Muscles.","authors":"Xiao Liu, Xiang Zhou, Zunfeng Liu","doi":"10.1021/acs.accounts.4c00842","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00842","url":null,"abstract":"<p><p>ConspectusLiquid crystal elastomer fibers (LCEFs) are reversible artificial muscles capable of stimuli-responsive functions, making them promising competitors for ideal soft actuators. These remarkable actuation properties depend strongly on their mechanical properties, such as elastic modulus and breaking stress. It is necessary to strengthen the LCEF muscles to meet the demands of advanced applications. However, despite the significant progress in LCEFs, there is currently no such Account systematically summarizing and analyzing the strategies adopted for enhancing their mechanical and actuation properties. The intuitive variations among the different enhancement strategies further call for investigations into how to choose the most suitable ones based on specific situations. In this Account, for the first time, we systematically summarize existing approaches to strengthening LCEF-based artificial muscles, contributing to the development of more robust and smarter fibrous artificial muscles.In the first section, we focus on the latest and most valuable progress on strengthening LCEF-based artificial muscles, highlighting the need for a comprehensive summary of the various approaches utilized. The mechanical properties of LCEFs can be tailored through molecular design, physical interactions, and fiber integration. The adjustment of hard/soft segment features, the introduction of additional microstructures, and the fiber integration provide opportunities to strengthen LCEF-based artificial muscles, which are discussed in the second section. Subsequently, we delve into the impact of various preparation methods on the performance of LCEFs, and LCEFs fabricated by different spinning and alignment techniques exhibited rather different mechanical and actuation properties. This has been adopted to engineer novel, stronger, and tailored fibrous artificial muscles, as described in the third section. Moreover, we show that the incorporation of rigid composite materials via coating and doping has emerged as a powerful strategy to strengthen LCEFs, such as core-shell structures. Such enhancements also introduce multifunctionality for LCE-based artificial muscles that can enrich the fiber structure and actuation mechanism, which are elucidated in the fourth section. Finally, we conclude this Account with a critical analysis of the challenges and prospects of LCE-based artificial muscles, hoping to pave the way for the construction of more powerful fibrous artificial muscles.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555260","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":"Diversity-Generating Skeletal Editing Transformations.","authors":"Fu-Peng Wu, Jasper L Tyler, Frank Glorius","doi":"10.1021/acs.accounts.4c00820","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00820","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusSkeletal editing, as a synthetic tool, offers the unique potential to selectively and efficiently modify the core skeleton of a target molecule at a late-stage. The main benefit of such transformations is the rapid exploration of the chemical space around lead compounds without necessitating a &lt;i&gt;de novo&lt;/i&gt; synthesis for each new molecule. However, many skeletal editing transformations are inherently restricted to generating a single product from a single starting compound, limiting the potential for diversification, a concept central to expediting structure-activity relationship (SAR) investigations. In this Account, we describe our efforts to develop novel skeletal editing transformations in which a modification to the central motif of a molecule is performed simultaneously with the incorporation of additional functionality that can be easily varied through a judicious choice of the reagents. Specifically, we successfully developed an α-iodonium diazo-based carbynyl radical equivalent reagent that, under photoredox conditions, could facilitate the ring-expansion of indene scaffolds while enabling the insertion of over ten different functionalized carbon atoms into the corresponding naphthalene products. This concept was later extended to the design of an atomic carbon equivalent reagent that could promote mild and selective Ciamician-Dennstedt-type indole ring-expansion reactions, while simultaneously installing an oxime ester handle that could undergo further functionalization. Furthermore, we highlight recent work from our group on multiple-atom insertion reactions, namely, the development of a photocatalyzed De Mayo reaction for the ring-expansion of cyclic ketones and a photocatalyzed dearomative ring-expansion of thiophenes via small-ring insertion. In both of these cases, multiple products can be potentially accessed from a single starting material upon variation of the insertion reagent. The diversity-generating skeletal editing strategy could also be applied to single-atom transmutation, as demonstrated by the development of a nitrogen-to-functionalized carbon atom transmutation reaction to convert pyridine to benzene rings. Here, the desired transformation was achieved via a sequence of pyridine ring-opening, Horner-Wadsworth-Emmons (HWE) olefination, and ring-closure, with a judicious choice of the HWE reagent allowing the installation of a wide variety of versatile functional groups. Finally, an energy transfer-mediated quinoline ring-contraction is discussed, specifically with reference to the ways in which it does and does not fit the criteria of a skeletal editing reaction. Although formal atom deletion transformations are typically restricted to single products from each discrete substrate, this [2 + 2] cycloaddition/rearrangement cascade also involves the incorporation of an alkene into the molecule and introduces a point of variation that can be exploited for diversity generation. We hope to not only highlight ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555258","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":"Biological Polymers: Evolution, Function, and Significance.","authors":"Kavita Matange, Eliav Marland, Moran Frenkel-Pinter, Loren Dean Williams","doi":"10.1021/acs.accounts.4c00546","DOIUrl":"10.1021/acs.accounts.4c00546","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusA holistic description of biopolymers and their evolutionary origins will contribute to our understanding of biochemistry, biology, the origins of life, and signatures of life outside our planet. While biopolymer sequences evolve through known Darwinian processes, the origins of the backbones of polypeptides, polynucleotides, and polyglycans are less certain. We frame this topic through two questions: (i) Do the characteristics of biopolymer backbones indicate evolutionary origins? (ii) Are there reasonable mechanistic models of such pre-Darwinian evolutionary processes? To address these questions, we have established criteria to distinguish chemical species produced by evolutionary mechanisms from those formed by nonevolutionary physical, chemical, or geological processes. We compile and evaluate properties shared by all biopolymer backbones rather than isolating a single type. Polypeptide, polynucleotide, and polyglycan backbones are kinetically trapped and thermodynamically unstable in aqueous media. Each biopolymer forms a variety of elaborate assemblies with diverse functions, a phenomenon we call polyfunction. Each backbone changes structure and function upon subtle chemical changes such as the reduction of ribose or a change in the linkage site or stereochemistry of polymerized glucose, a phenomenon we call function-switching. Biopolymers display homo- and heterocomplementarity, enabling atomic-level control of structure and function. Biopolymer backbones access recalcitrant states, where assembly modulates kinetics and thermodynamics of hydrolysis. Biopolymers are emergent; the properties of biological building blocks change significantly upon polymerization. In cells, biopolymers compose mutualistic networks; a cell is an Amazon Jungle of molecules. We conclude that biopolymer backbones exhibit hallmarks of evolution. Neither chemical, physical, nor geological processes can produce molecules consistent with observations. We are faced with the paradox that Darwinian evolution relies on evolved backbones but cannot alter biopolymer backbones. This Darwinian constraint is underlined by the observation that across the tree of life, ribosomes are everywhere and always have been composed of RNA and protein. Our data suggest that chemical species on the Hadean Earth underwent non-Darwinian coevolution driven in part by hydrolytic stress, ultimately leading to biopolymer backbones. We argue that highly evolved biopolymer backbones facilitated a seamless transition from chemical to Darwinian evolution. This model challenges convention, where backbones are products of direct prebiotic synthesis. In conventional models, biopolymer backbones retain vestiges of prebiotic chemistry. Our findings, however, align with models where chemical species underwent iterative and recursive sculpting, selection, and exaptation. This model supports Orgel's \"gloomy\" prediction that modern biochemistry has discarded vestiges of prebiotic chemistry. B","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"659-672"},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187498","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":"Buckybowl-Based Nanocarbons: Synthesis, Properties, and Applications.","authors":"Yan Chen, Lei Zhang","doi":"10.1021/acs.accounts.4c00812","DOIUrl":"10.1021/acs.accounts.4c00812","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusThe introduction of a five-membered ring into hexagon-fused networks typically induces strain that causes positive Gaussian curvature, leading to bowl-shaped polycyclic aromatic hydrocarbons (PAHs), often referred to as buckybowls or π-bowls. The interest in buckybowls is derived from their intriguing properties including, but not limited to, pyramidalized sp&lt;sup&gt;2&lt;/sup&gt; carbon atoms, low-lying lowest unoccupied molecular orbital (LUMO), surface charge stabilization, and bowl-to-bowl inversion. In recent years, investigations into the functionalization of buckybowls, as well as the structural aspects related to properties, have made significant progress. Indeed, the functionalization of buckybowls is a major route to increase structural diversity and fine-tune their properties. In particular, the fusion of aromatic rings to buckybowl rims (π-extension of buckybowls) has established a particularly promising synthetic strategy to access a wide range of buckybowl-based nanostructures with unique topologies and properties. A major obstacle, however, is the limited number of appropriate buckybowls, which could be suggested as potential frameworks for further functionalization. Moreover, buckybowls have been typically synthesized by ring-closing reactions, but many of these procedures suffer from the occurrence of considerable strain and lead to an undesired rearrangement. As a result, the development of buckybowl-based nanocarbons with desirable properties is still in its infancy due to the limited structural diversity, functionalization, and scalability.This Account describes our recent progress in the synthesis of buckybowls and buckybowl-based nanocarbons. In our study, diindeno[4,3,2,1-&lt;i&gt;fghi&lt;/i&gt;:4',3',2',1'-&lt;i&gt;opqr&lt;/i&gt;]perylene (&lt;b&gt;DIP&lt;/b&gt;), pyracyleno[6,5,4,3,2,1-&lt;i&gt;pqrstuv&lt;/i&gt;]pentaphene (&lt;b&gt;PP&lt;/b&gt;), tetracyclopenta[&lt;i&gt;cd&lt;/i&gt;,&lt;i&gt;fg&lt;/i&gt;,&lt;i&gt;jk&lt;/i&gt;,&lt;i&gt;mn&lt;/i&gt;]pyrene (&lt;b&gt;TPP&lt;/b&gt;), and corannulene are employed as basic structural units, which exhibit a bowl-shaped geometry and offer an ideal platform for functionalization. General bottom-up approaches have been used to access buckybowl derivatives functionalized with peripheral alkynyl and aryl groups. These substituent groups significantly influence solubility, energy levels, and crystal packing, all of which impact their performance. These buckybowls are ultimately converted into π-extended nanocarbons with wide-ranging structural diversity, including doubly curved, rippled, and chiral nanocarbons. Chiral buckybowl-based nanocarbons, where chirality is introduced from quasi-[8]circulene moieties, have high enantiomerization barriers, enabling the separation of the enantiomers. Notably, the rippled nanocarbon containing 10 aromatic rings directly fused to the &lt;b&gt;TPP&lt;/b&gt; core exhibits attractive electronic, magnetic, and mechanical properties, which can be further functionalized through the use of well-established chemistry, opening up many possibilities to access unusual carbon allo","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"762-776"},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466529","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}