Accounts of Chemical Research最新文献

{"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":"<p><p>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":"","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":"","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":"<p><p>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<sup>2</sup> 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-<i>fghi</i>:4',3',2',1'-<i>opqr</i>]perylene (<b>DIP</b>), pyracyleno[6,5,4,3,2,1-<i>pqrstuv</i>]pentaphene (<b>PP</b>), tetracyclopenta[<i>cd</i>,<i>fg</i>,<i>jk</i>,<i>mn</i>]pyrene (<b>TPP</b>), 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 <b>TPP</b> 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}

{"title":"Poly(Aryl-<i>co</i>-Aryl Piperidinium) Copolymers for Anion Exchange Membrane Fuel Cells and Water Electrolyzers.","authors":"Nanjun Chen, Chuan Hu, Young Moo Lee","doi":"10.1021/acs.accounts.4c00695","DOIUrl":"10.1021/acs.accounts.4c00695","url":null,"abstract":"<p><p>Next-generation cost-effective anion exchange membrane (AEM) fuel cells (AEMFCs) and AEM water electrolyzers (AEMWEs) have emerged as promising alternatives to costly proton exchange membrane (PEM) fuel cells and water electrolyzers due to the possibility of utilizing platinum-group-metal (PGM)-free catalysts and phasing out unsustainable perfluorosulfonic acid polymers. Anion exchange polyelectrolytes (AEPs), which can be utilized as AEMs or ionomers, are pivotal materials in AEM devices. Despite extensive exploration in the past decade, the application of AEPs has been significantly impeded by their poor ionic conductivity, insufficient alkaline stability, and unfavorable mechanical properties. Therefore, developing highly conductive and robust AEPs is critical to the success of AEMFCs and AEMWEs. (i) Our group has developed a series of highly conductive and durable poly(aryl-<i>co</i>-aryl piperidinium) (c-PAP) AEPs to address the aforementioned issues. c-PAP AEMs and ionomers enable outstanding OH^- conductivity (>160 mS cm^-1 at 80 °C), alkaline stability (1 M NaOH at 80 °C > 2000 h), dimensional stability, and mechanical properties (tensile strength > 80 MPa), giving them all the properties required for applications in AEM devices. (ii) Based on c-PAP AEMs and ionomers, we have developed high-performance AEMFCs and AEMWEs, as well as provided insights into the ionomer research and the design of membrane electrode assemblies. Typically, c-PAP AEMFCs reached the topmost peak power densities (PPDs) of 2.7 W cm^-2 at 80 °C in H₂-O₂ along with 1000 h cell durability. Moreover, cathode-dried AEMWEs achieved a record-breaking current density of 17 A cm^-2 in 1 M KOH, and the cell can be run stably at a 1.5 A cm^-2 current density for over 2000 h. The remarkable performances achieved by this new class of c-PAP AEPs identify them as the most promising candidates for practical applications in AEMFCs and AEMWEs. In this account, we will elaborate on our strategies and methodologies associated with c-PAP AEPs and AEM devices, covering the screening and identification of highly durable cation head groups and molecular-engineering approaches to design c-PAP AEMs and ionomers. Moreover, we underscore our strategy in terms of developing highly efficient and durable AEMFCs and AEMWEs. We also elucidate different approaches for further enhancing the ion conductivity and mechanical stability of c-PAP AEMs, including the design of backbones and side chains, cross-linking, and reinforcement. We firmly believe that our series of studies has made substantial contributions to the fields of AEM, ionomers, AEMFCs, and AEMWEs, which have advanced AEM technology to be on par with PEM technology, opening a new avenue for commercialization of AEMFCs and AEMWEs.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"688-702"},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389488","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":"Electrochemical Sensing Mechanisms and Interfacial Design Strategies of Mesoporous Nanochannel Membranes in Biosensing Applications.","authors":"Hui Zeng, Kang Liang, Lei Jiang, Dongyuan Zhao, Biao Kong","doi":"10.1021/acs.accounts.4c00764","DOIUrl":"10.1021/acs.accounts.4c00764","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusPrecise and rapid detection of key biomolecules is crucial for early clinical diagnosis. These critical biomolecules and biomarkers are typically present at low concentrations within complex environments, presenting significant challenges for their accurate and reliable detection. Nowadays, electrochemical sensors based on nanochannel membranes have attracted significant attention due to their high sensitivity, simplicity, rapid response, and label-free point-of-care detection capabilities. The confined arena provided by the nanochannels for target recognition and interactions facilitates detection and signal amplification, leading to enhanced detection performance. The nanochannel membranes also can act as filters to repel the interferents and enable target detection in more complex environments. Thus, sensors based on nanochannel membranes are considered promising platforms for biosensing applications. However, challenges such as uncontrollable structures and unstable performance in some materials limit their applications and theoretical advancements. To investigate the relationship between architecture and sensing performance and to achieve reliable and efficient performance, it is essential to construct sensors with precise nanostructures possessing stable properties. With the development of nanomaterials technology, mesoporous nanochannel membranes with robust, controllable, and ordered mesostructures, along with tunable surface properties and tailored ion transport dynamics, have emerged as promising candidates for achieving reliable and efficient biosensing performance. Additionally, investigating the sensing mechanisms and key influencing factors will provide valuable insights into optimizing sensor architecture and enhancing the efficiency and reliability of biosensing technologies. In this Account, we highlight substantial advancements in mesoporous nanochannel membranes, which are mainly based on the research work published by our group. In the first section, we explore the underlying mechanisms of the sensing processes, including the solid-liquid interfacial interactions and nanoconfinement effects (i.e., electrostatic interactions, hydrophilic/hydrophobic interactions, and steric hindrance effects). We also delve into the key parameters including geometry, materials, recognition elements, and external factors related to mesoporous nanochannel membranes and their impacts on sensing mechanisms and performance. In particular, we point out that mesoporous nanochannel membranes with three-dimensional interconnected networks can facilitate ion penetration and lead to an increased number of binding sites, contributing to high sensitivity. Additionally, composite or multilevel mesoporous nanochannel membranes, particularly when integrated with external stimuli such as pH, light, and heat, can introduce unexpected properties, enhancing the sensing performance. These understandings provide valuable insights into the fundamental","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"732-745"},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253971","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":"Designing Functional and Responsive Molecules with Boronic Acids.","authors":"João P M António, Inês L Roque, Fábio M F Santos, Pedro M P Gois","doi":"10.1021/acs.accounts.4c00691","DOIUrl":"10.1021/acs.accounts.4c00691","url":null,"abstract":"<p><p>ConspectusBoronic acids (BAs) are one of the most important classes of reagents in modern synthesis, enabling a wide range of powerful transformations that facilitate the formation of key carbon-carbon and carbon-heteroatom bonds. While their success as reagents is well-known, their remarkable potential as building blocks for creating functional molecules is often overlooked.At the core of BAs' uniqueness is their ability to form reversible covalent bonds, thanks to the interconversion of the boron atom between its uncharged trigonal planar structure and an anionic sp³-hybridized form. This coordination chemistry has paved the way for exciting developments in fields such as medicinal chemistry and chemical biology. In recent years, BAs have been used to create a wide variety of materials, including small-molecule drugs, bioconjugates, drug delivery vehicles, polymeric nanomaterials, sensors, and even photosensitizers. What makes this strategy particularly unique is the structural diversity that can be achieved by functionalizing the BA coordination sphere, along with the possibility of incorporating stimuli-responsive mechanisms. This reactivity is further enhanced by the well-known oxidation of BAs in the presence of reactive oxygen species (ROS).A detailed understanding of the mechanisms governing the dynamic nature of BAs enables the engineering of sophisticated materials that can respond to specific molecular stimuli, such as changes in pH, carbohydrate or glutathione concentrations, and hydrogen peroxide. These stimuli are often key indicators of diseases such as cancer, inflammation, and neurodegeneration, placing BAs at the forefront of tools for designing materials that can potentially influence the mechanisms behind these diseases.In this Account, we draw on our group's expertise to explore the exciting potential of BAs in the design of functional materials. The focus is on the response of different boron complexes to biologically relevant stimuli. We describe the preparation of boronated esters (BEs), BA-salicylhydroxamic acid (BA-SHA) complexes, iminoboronates, diazaborines, and boronated thiazolidines and discuss how these chemotypes respond to disease-relevant triggers. Given the growing importance of using external stimuli to control the efficacy of modern drugs, we also explore how some of these compounds respond to specific chemicals. While this Account is not meant to be an exhaustive survey of every example of BA stimulus-responsiveness, we aim to integrate existing chemotypes and their chemical triggers. Our goal is to provide an overview of the mechanisms enabled by BAs for designing functional materials that could one day lead to innovative therapeutic options for human diseases.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"673-687"},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404874","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":"Covalent Metal-Organic Frameworks: Fusion of Covalent Organic Frameworks and Metal-Organic Frameworks.","authors":"Rong-Jia Wei, Xiao Luo, Guo-Hong Ning, Dan Li","doi":"10.1021/acs.accounts.4c00774","DOIUrl":"10.1021/acs.accounts.4c00774","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusMetal-organic frameworks (MOFs) and covalent organic frameworks (COFs), as emerging porous crystalline materials, have attracted remarkable attention in chemistry, physics, and materials science. MOFs are constructed by metal clusters (or ions) and organic linkers through coordination bonds, while COFs are prepared by pure organic building blocks via covalent bonds. Because of the nature of linkages, MOFs and COFs have their own shortcomings. Typically, the relatively weak bond strengths of coordination bonds lead to poor chemical stability of MOFs, which limits their practical implementations. On the other hand, due to the strong covalent bonds, COFs exhibit rather higher stability under harsh conditions, compared to MOFs. However, the lack of open metal sites restricts their functionalization and application. Therefore, it is hypothesized that the \"cream-skimming\" of MOFs and COFs would address these drawbacks and produce a new class of crystalline porous material, namely, covalent metal-organic frameworks (CMOFs), with unprecedented structural complexity and advanced functionality. The CMOFs reveal a new synthetic approach for the preparation of reticular materials. Specifically, metal ions are reacted with chelating ligands to assemble metal complexes or clusters with functional reactive sites (e.g., -CHO, and -NH&lt;sub&gt;2&lt;/sub&gt;), which can be further connected with organic linkers to form networked structures via dynamic covalent chemistry (DCC). The isolated metal complex or cluster precursors show enhanced stability which prevents structural decomposition and rearrangements during the self-assembly process of CMOFs. Since the topology of preassembled metal nodes is well-defined, the CMOFs structure can be readily predicted upon directed networking of covalent bonds. Unaccessible reticular materials from unstable or highly reactive metal ion/clusters under traditional conditions can be prepared via the DCC approach. Moreover, CMOFs synergize the advantages of MOFs and COFs, containing metal active sites ensuring various interesting properties, and covalent linkages that allow rather high chemical stability even under harsh conditions. In the past few years, our group has specifically focused on the development of general synthetic strategies for CMOFs by networking coinage metal (Cu, Ag, and Au)-based cyclic trinuclear units (CTUs) with DCC. The CTUs exhibit trigonal planar structures and can be functionalized with reactive sites, such as -NH&lt;sub&gt;2&lt;/sub&gt; and -CHO, that can further react with organic linkers to afford CMOFs. Notably, CTUs also features interesting properties including metallophilic attraction, π-acidity/basicity, luminescence, redox activity and catalytic activity, which can be incorporated into CMOFs. Therefore, we envision that CMOFs would be promising platforms not only for the development of novel reticular materials, but also for potential applications in many research fields including gas absorption/separa","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"746-761"},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466531","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":"Heterophase Junction Effect on Photogenerated Charge Separation in Photocatalysis and Photoelectrocatalysis.","authors":"Jing Zhang, Xiuli Wang, Xiang Wang, Can Li","doi":"10.1021/acs.accounts.4c00582","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00582","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusThe conversion of solar energy into chemical energy is promising to address energy and environmental crises. For solar conversion processes, such as photocatalysis and photoelectrocatalysis, a deep understanding of the separation of photogenerated charges is pivotal for advancing material design and efficiency enhancement in solar energy conversion. Formation of a heterophase junction is an efficient strategy to improve photogenerated charge separation of photo(electro)catalysts for solar energy conversion processes. A heterophase junction is formed at the interface between the semiconductors possessing the same chemical composition with similar crystalline phase structures but slightly different energy bands. Despite the small offset of Fermi levels between the different phases, a built-in electric field is established at the interface of the heterophase junction, which can be the driving force for the photogenerated charge separation at the nanometer scale. Notably, slight variations in the energy band of the two crystalline phases result in small energy barriers for the photogenerated carrier transfer. Moreover, the structural similarity of the two different crystalline phases of a semiconductor could minimize the lattice mismatch at the heterophase junction, distinguishing it from a p/n junction or heterojunction formed between two very different semiconductors.This Account provides an overview of the understanding, design, and application of heterophase junctions in photocatalysis and photoelectrocatalysis. It begins with a conceptualization of the heterophase junction and reviews recent advances in the synthesis of semiconductors with a heterophase junction. The phase transformation method with the advantage of forming a heterophase junction with an atomically matched interface and the secondary seed growth method for unique structures with excellent electronic and optoelectronic properties are described. Furthermore, the mechanism of the heterophase junction for improving the photogenerated charge separation is discussed, followed by a comprehensive discussion of the structure-activity relationship for the heterophase junction. The home-built spatially resolved and time-resolved spectroscopies offer direct imaging of the built-in electric field across the heterophase junction and then the direct detection of the photogenerated charge transfer between the two crystalline phases driven by the built-in electric field. Such an efficient interfacial charge transfer results in the improvement of the photogenerated charge separation, a higher yield of long-lived charges, and thus the inhibition of the charge recombination. Benefiting from these insights, structural design strategies for the heterophase junction, such as precise tuning of band alignment, exposed heterophase amounts, phase alignment, and interface structure, have been developed. Finally, the challenges, opportunities, and perspectives of heterophase junctions in the","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539353","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":"Activation of Molecular Oxygen and Selective Oxidation with Metal Complexes.","authors":"Chao Wang, Jianliang Xiao","doi":"10.1021/acs.accounts.4c00731","DOIUrl":"10.1021/acs.accounts.4c00731","url":null,"abstract":"<p><p>ConspectusSelective oxidation with molecular oxygen is one of the most appealing approaches to functionalization of organic molecules and, yet at the same time, one of the most challenging reactions facing organic synthesis due to poor selectivity control. Molecular oxygen is a green and inexpensive oxidant, producing water as the only byproduct in oxidation. Not surprisingly, it has been used in the manufacturing of many commodity chemicals in the industry. It is also nature's choice of oxidant and drives a variety of oxidation reactions critical to life and various other biologic processes. While the past decades have witnessed great progress in understanding, both structurally and mechanistically, how nature exploits metalloenzymes, i.e., monooxygenases and dioxygenases, to tackle some of the most challenging oxidation reactions, e.g., methane oxidation to methanol, there are only a small number of well-defined, man-made metal complexes that have been reported to enable selective oxidation with molecular oxygen of compounds more relevant to fine chemical and pharmaceutical synthesis.In the past 10 years or so, our laboratories have developed several transition metal complexes and shown that they are capable of catalyzing selective oxidation under 1 atm of O₂. Thus, we have shown that an Fe(II)-bisimidazolidinyl-pyridine complex catalyzes selective oxygenation of C-H bonds in ethers with concomitant release of hydrogen gas instead of water, and when the iron center is replaced with Fe(III), selective oxidative cleavage of C═C bonds of olefins becomes feasible. To address the low activity of the iron complex in oxidizing less active olefins, we have developed a Mn(II)-bipyridine complex, which catalyzes oxidative cleavage of C═C bonds in aliphatic olefins, C-C bonds in diols, and carboxyl units in carboxylic acids under visible light irradiation. Light is necessary in the oxidation to cleave an off-cycle, inactive manganese dimer into a catalytically active Mn═O oxo species. Furthermore, we have found that a binuclear salicylate-bridged Cu(II) complex enables the C-H oxidation of tetrahydroisoquinolines as well as C═C bond cleavage, and when a catalytic vitamin B1 analogue is brought in, oxygenation of tetrahydroisoquinolines to lactams takes place via carbene catalysis. Still further, we have found that a readily accessible binuclear Rh(II)-terpyridine complex catalyzes the oxidation of alcohols, and being water-soluble, the catalyst can be easily separated and reused multiple times. In addition, we recently unearthed a simple protocol that allows waste polystyrene to be depolymerized to isolable, valuable chemicals. A cheap Brønsted acid acts as the catalyst, activating molecular oxygen to a singlet state through complexation with the polymer under light irradiation, thereby depolymerizing the polymer.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"714-731"},"PeriodicalIF":16.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466399","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":"The Photoactivated Depot (PAD): Light Triggered Control of Therapeutic Protein Solubility and Release.","authors":"Simon H Friedman","doi":"10.1021/acs.accounts.4c00718","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00718","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusMany therapeutic proteins can benefit from controlling the timing and amount of their release. This is especially true for signaling molecules such as insulin, whose requirements vary continually throughout the day. Currently, the only way to provide this variable delivery is through a pump. Pumps, and their required cannulas/needles, introduce a wide range of problems, including cannula occlusion, infection, and biofouling. We have instead pursued the photoactivated depot or PAD approach, in which therapeutic proteins are released into the body through light activation of shallow, skin-based depots that are activated by small LED light sources ( &lt;i&gt;Angew. Chem.&lt;/i&gt; 2013, 125(5), 1444-1449, &lt;i&gt;Mol. Pharmaceutics&lt;/i&gt; 2016, 13(11), 3835-3841, &lt;i&gt;J. Am. Chem. Soc.&lt;/i&gt; 2017, 139(49), 17861-17869, &lt;i&gt;ACS Biomater Sci. Eng.&lt;/i&gt; 2021, 7(4), 1506-1514, and &lt;i&gt;ACS Biomater Sci. Eng.&lt;/i&gt; 2024, 10(6), 3806-3812). By linking protein release to transcutaneous irradiation, we can control the amount and timing of therapeutic release by varying the amount and timing of irradiation. At the heart of this approach are PAD materials that contain three key elements: the therapeutic protein, a photocleavable (PC) group, and a solubility reducing moiety. This latter element is needed to allow the PAD material to stay at the site of injection, so that light can be effectively directed to it. The light causes the PC group to break its bond with the therapeutic protein, which can then diffuse into the capillary bed and be absorbed into systemic circulation. We have pursued four distinct methods of achieving solubility reduction prior to irradiation. The first approach is to use a highly insoluble polymer that is linked to the therapeutic protein via the PC group. This was the approach we used in our first attempt at making a PAD material and proved to be effective in both in vitro and in vivo settings. The main challenge with this first approach is that the polymer is left in the body after the protein is released, necessitating additional optimization to clear it, using biodegradation. In addition, it is very inefficient, with only a minority of the material being the therapeutic. In the second approach, we created polymers/oligomers out of the protein, using small light-cleaved links. The simplest of these, a trimer of proteins linked to a central core, is 90% therapeutic, and retains the preirradiation insolubility required of the PAD approach. In the third approach, we link charged groups to the protein to shift its iso-electric point, such that the material will be insoluble (and hence able to form a depot) at pH 7, but will release native, active protein after photolysis cleaves off the charged groups. Finally, in the fourth approach, we confer insolubility by attaching highly nonpolar groups to the therapeutic protein via a PC linkage. In this article, the challenges, strengths and weaknesses of each of these approaches will be described, and guidan","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539365","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":"Correction to “Predicting and Understanding Noncovalent Interactions Using Novel Forms of Symmetry-Adapted Perturbation Theory”","authors":"Kevin Carter-Fenk, Ka Un Lao, John M. Herbert","doi":"10.1021/acs.accounts.5c00107","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00107","url":null,"abstract":"In a previous Account, (1) we surveyed the use of extended symmetry-adapted perturbation theory (XSAPT), a family of methods for computing accurate intermolecular interaction energies and components thereof. In considering π-stacking interactions, we made comparisons between the XSAPT + many-body dispersion (MBD) method and a model potential introduced in a seminal paper on π–π interactions by Hunter and Sanders (HS). (2) Unfortunately, our implementation of the HS model contained an error in the van der Waals (vdW) term, which is corrected here alongside some additional clarifications. Because there are subtleties in how the vdW parameters were originally reported, (2) as well as ambiguity regarding which point charges constitute the HS model, (2,3) additional details are provided here. The HS model consists of a point-charge electrostatic term (&lt;i&gt;E&lt;/i&gt;&lt;sub&gt;elst&lt;/sub&gt;&lt;sup&gt;Q&lt;/sup&gt;) and a vdW term (&lt;i&gt;E&lt;/i&gt;&lt;sub&gt;vdW&lt;/sub&gt;), There is some ambiguity regarding the point charges to be used in &lt;i&gt;E&lt;/i&gt;&lt;sub&gt;elst&lt;/sub&gt;&lt;sup&gt;Q&lt;/sup&gt;. What is clear is that the HS model contains atom-centered point charges for carbon atoms within the π-system (&lt;i&gt;q&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt;) along with out-of-plane displaced charges (&lt;i&gt;q&lt;/i&gt;&lt;sub&gt;π&lt;/sub&gt;) to represent the π-electrons. In their original 1990 paper, HS first discuss “unpolarized” or “idealized” charges, in which carbon atoms within the π-system are described by charges &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt; = +1.0 and &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;π&lt;/sub&gt; = −0.5 (in atomic units). (2) The π charges are displaced from the nuclei by δ = 0.47 Å, both above and below the arene plane, a value that is determined in order to reproduce the experimental quadrupole moment of C&lt;sub&gt;6&lt;/sub&gt;H&lt;sub&gt;6&lt;/sub&gt;. (5) Although the HS paper includes a discussion of polarizing this idealized framework, no actual values for hydrogen-atom charges are provided in ref (2). Moreover, Figure 3 of ref (2) depicts only &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt; = +1.0 and &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;π&lt;/sub&gt; = −0.5, with no indication that there are charges on the hydrogen atoms. In 1991, Hunter et al. (3) suggested a model in which the charge on carbon is reduced to &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt; = +0.95 and a charge &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;H&lt;/sub&gt; = +0.05 is placed on hydrogen, retaining &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;π&lt;/sub&gt; = −0.5. This scheme (in Figure 3 of ref (3)) is attributed to the original HS model even though the value of &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;H&lt;/sub&gt; was not provided in the original. In other work by Hunter and co-workers, only &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt; and &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;π&lt;/sub&gt; are discussed, e.g., in Figure 3 of ref (6). These ambiguities are consistent with widespread confusion in the literature regarding what the HS model actually is, as discussed elsewhere. (7) For this Correction, we implemented &lt;i&gt;E&lt;/i&gt;&lt;sub&gt;elst&lt;/sub&gt;&lt;sup&gt;Q&lt;/sup&gt; according to ref (3) using &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt; = +0.95, &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;H&lt;/sub&gt; = +0.05, and &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;π&lt;/sub&gt; = −0.5. For (C&lt;sub&gt;6&lt;/sub&gt;H&lt;sub&gt;6&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;, the presence or absence of &lt;i&gt;q&lt;/i&gt;&lt;sub&gt;H&lt;/sub&gt; makes only a mi","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"49 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532315","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}