Accounts of Chemical Research最新文献

Solar-to-electrochemical energy storage is one of the essential solar energy utilization pathways alongside solar-to-electricity and solar-to-chemical conversion. A coupled solar battery enables direct solar-to-electrochemical energy storage via photocoupled ion transfer using photoelectrochemical materials with light absorption/charge transfer and redox capabilities. Common photoelectrochemical materials face challenges due to insufficient solar spectrum utilization, which restricts their redox potential window and constrains energy conversion efficiency. In contrast, molecular photoelectrochemical energy storage materials are promising for their mechanism of exciton-involved redox reaction that allows for extra energy utilization from hot excitons generated by superbandgap excitation and localized heat after absorption of sub-bandgap photons. This enables more efficient redox reactions with a less restricted redox potentials window and, thus, better utilization of the full solar spectrum. Despite these advantages, practical application remains elusive due to the mismatch between the short lifetime of the charge separation state (<ns) and the slower redox reaction rate (>μs). This mismatch results in a significant portion of the photogenerated charges recombining before participating in desired electrochemical energy storage reactions, leading to diminished overall efficiency. It is therefore highly important to develop molecular materials with intrinsic prolonged charge separation state and extrinsic effective mass-electron transfer to enable efficient coupled solar batteries for practical applications.

In this Account, we begin with an introduction of the general solar-to-electrochemical energy storage concept based on molecular photoelectrochemical energy storage materials, highlighting the advantages of periodic oxidative donor-reductive acceptor porous aggregate structures that have synergistic implications on charge separation state lifetime extension and mass-electron transfer. We then present our earliest trial on the design and application of molecular photoelectrochemical energy storage materials, which stimulated our subsequent studies on tuning electron donor and acceptor structures for enhanced charge separation and diverse photoelectrochemical redox reactions. Moreover, we introduce the best practices in the design and assembly of various coupled solar battery devices, along with our literature contributions and progresses in solar-to-electrochemical energy storage efficiency (η_SES) over nearly the past decade. Finally, we conclude by highlighting the universality of our strategies as essential design principles, spanning from regulating long-lived charge separation states and photocoupled ion transfer processes in molecular materials to the construction of efficient coupled solar batteries. We offer perspectives on the synergy between photovoltage and redox potentials and the practical significance of 3

Over the past two decades, we have developed a series of pincer-type transition metal complexes capable of activating strong covalent bonds through a mode of reactivity known as metal–ligand cooperation (MLC). In such systems, an incoming substrate molecule simultaneously interacts with both the metal center and ligand backbone, with one part of the molecule reacting at the metal center and another part at the ligand. The majority of these complexes feature pincer ligands with a pyridine core, and undergo MLC through reversible dearomatization/aromatization of this pyridine moiety. This MLC platform has enabled us to perform a variety of catalytic dehydrogenation, hydrogenation, and related reactions, with high efficiency and selectivity under relatively mild conditions.

In a typical catalytic complex that operates through MLC, the cooperative ligand remains coordinated to the metal center throughout the entire catalytic process, and this complex is the only catalytic species involved in the reaction. As part of our ongoing efforts to develop new catalytic systems featuring MLC, we have recently introduced the concept of transient cooperative ligand (TCL), i.e., a ligand that is capable of MLC when coordinated to a metal center, but the coordination of which is reversible rather than permanent. We have thus far employed thiol(ate)s as TCLs, in conjunction with an acridanide-based ruthenium(II)-pincer catalyst, and this has resulted in remarkable acceleration and inhibition effects in various hydrogenation and dehydrogenation reactions. A cooperative thiol(ate) ligand can be installed in situ by the simple addition of an appropriate thiol in an amount equivalent to the catalyst, and this has been repeatedly shown to enable efficient bond activation by MLC without the need for other additives, such as base. The use of an ancillary thiol ligand that is not fixed to the pincer backbone allows the catalytic system to benefit from a high degree of tunability, easily implemented by varying the added thiol. Importantly, thiols are coordinatively labile enough under typical catalytic conditions to leave a meaningful portion of the catalyst in its original unsaturated form, thereby allowing it to carry out its own characteristic catalytic activity. This generates two coexisting catalyst populations─one that contains a thiol(ate) ligand and another that does not─and this may lead to different catalytic outcomes, namely, enhancement of the original catalytic activity, inhibition of this activity, or the occurrence of diverging reactivities within the same catalytic reaction mixture. These thiol effects have enabled us to achieve a series of unique transformations, such as thiol-accelerated base-free aqueous methanol reforming, controlled stereodivergent semihydrogenation of alkynes using thiol as a reversible catalyst inhibitor, and hydrogenative perdeuteration of C═C bonds without using D₂, enabled by a combination of thi

Stereochemistry has played a key role in the development of synthetic chemistry for the simple reason that the function and properties of most molecules, from medicine to materials science, depend on their shape and thus the stereoisomer used. However, despite the potential for rotaxanes and catenanes to display unusual forms of stereochemistry being identified as early as 1961, this aspect of the mechanical bond remained underexplored and underexploited; until 2014 it was only possible to access chiral rotaxanes and catenanes whose stereoisomerism is solely attributable to the mechanical bond using chiral stationary phase high performance liquid chromatography, which limited their production on scale and thus inhibited the investigation of their properties and applications. Furthermore, the stereogenic units of such molecules and analogues were often poorly described, which made it hard to fully articulate both what had been achieved in the field and what problems were left to solve. Relatively recently, methods to access rotaxanes and catenanes that display mechanical stereochemistry selectively have been developed, making these intriguing structures available for study in a range of prototypical applications including catalysis, sensing, and as chiral luminophores.

In this Account, we briefly discuss the history of mechanical stereochemistry, beginning in 1961 when the potential for mechanical stereoisomerism was first identified, before defining how mechanical stereochemistry arises from a structural point of view. Building on this, using simple stereochemical arguments, we confirm that the complete set of unique stereogenic units of two-component rotaxanes and catenanes have finally been identified and categorized unambiguously, with the last being identified only in 2024. After pausing to discuss some of the stereochemical curiosities that arise when molecules contain both covalent and mechanical stereogenic units, and the potential for stereoisomerism to arise due to co-conformational movement, we use our stereochemical framework to summarize our efforts to develop conceptually general approaches to [2]catenanes and [2]rotaxanes containing all of the possible mechanical stereogenic units. In particular, we highlight how the nature of a mechanical stereogenic unit affects the available strategies for their stereoselective synthesis. We finish by highlighting recent prototypical chemical applications of interlocked molecules that rely on their mechanical stereochemistry, before discussing future directions and challenges.

Taken together, we propose that the transition of such molecules from being hard to make and poorly described, to being available in high stereopurity using clearly articulated methodological and stereochemical concepts suggests that the field is finally maturing. Thus, we are now coming to the end of the beginning of mechanical stereochemistry. The stage is now set for such molecules to play a functional

Aromatic esters are cost-effective, versatile, and commonly used scaffolds that are readily synthesized or encountered as synthetic intermediates. While most conventional reactions involving these esters are nucleophilic acyl substitutions or 1,2-nucleophilic additions─where a nucleophile attacks the carbonyl group, decarbonylative transformations offer an alternative pathway by using the carbonyl group as a leaving group. This transition-metal-catalyzed process typically begins with oxidative addition of the C(acyl)–O bond to the metal. Subsequently, the reaction involves the migration of CO to the metal center, the reaction with a nucleophile, and reductive elimination to yield the final product. Pioneering work by Yamamoto on nickel complexes and the development of decarbonylative reactions (such as Mizoroki–Heck-type olefination) using aromatic carboxylic anhydrides catalyzed by palladium were conducted by de Vries and Stephan. Furthermore, reports have surfaced of decarbonylative hydrogenation of pyridyl methyl esters by Murai using ruthenium catalysts as well as Mizoroki–Heck-type reactions of nitro phenyl esters by Gooßen under palladium catalysis. Our group has been at the forefront of developing decarbonylative C–H arylations of phenyl esters with 1,3-azoles and aryl boronic acids using nickel catalysts. The key to this reaction is the use of phenyl esters, which are easy to synthesize, stabilize, and handle, allowing oxidative addition of the C(acyl)–O bond; nickel, which facilitates oxidative addition of the C(acyl)–O bond; and suitable bidentate phosphine ligands that can stabilize the intermediate. By modification of the nucleophiles, esters have been effectively utilized as electrophiles in cross-coupling reactions, encouraging the development of these nucleophiles among researchers. This Account summarizes our advancements in nucleophile development for decarbonylative coupling reactions, particularly highlighting the utilization of aromatic esters in diverse reactions such as alkenylation, intramolecular etherification, α-arylation of ketones, C–H arylation, methylation, and intramolecular C–H arylation for dibenzofuran synthesis, along with cyanation and reductive coupling. We also delve into reaction types that are distinct from typical decarbonylative reactions, including ester dance reactions, aromatic ring exchanges, and deoxygenative transformations, by focusing on the oxidative addition of the C(acyl)–O bond of the aromatic esters to the metal complex. For example, the ester dance reaction is hypothesized to undergo 1,2-translocation starting with oxidative addition to a palladium complex, leading to a sequence of ortho-deprotonation/decarbonylation, followed by protonation, carbonylation, and reductive elimination. The aromatic exchange reaction likely involves oxidative addition of complexes of different aryl electrophiles with a nickel complex. In deoxygenative coupling, an oxidative addition complex with pall

In human cells, intracellular access and therapeutic cargo transport, including gene-editing tools (e.g., CRISPR–Cas9 and transposons), nucleic acids (e.g., DNA, mRNA, and siRNA), peptides, and proteins (e.g., enzymes and antibodies), are tightly constrained to ensure healthy cell function and behavior. This principle is exemplified in the delivery mechanisms of chimeric antigen receptor (CAR)-T cells for ex-vivo immunotherapy. In particular, the clinical success of CAR-T cells has established a new standard of care by curing previously incurable blood cancers. The approach involves the delivery, typically via the use of electroporation (EP) and lentivirus, of therapeutic CAR genes into a patient’s own T cells, which are then engineered to express CARs that target and combat their blood cancer. But the key difficulty lies in genetically manipulating these cells without causing irreversible damage or loss of function─all the while minimizing complexities of manufacturing, safety concerns, and costs, and ensuring the efficacy of the final CAR-T cell product.

Nanoinjection─the process of intracellular delivery using nanoneedles (NNs)─is an emerging physical delivery route that efficiently negotiates the plasma membrane of many cell types, including primary human T cells. It occurs with minimal perturbation, invasiveness, and toxicity, with high efficiency and throughput at high spatial and temporal resolutions. Nanoinjection promises greatly improved delivery of a broad range of therapeutic cargos with little or no damage to those cargos. A nanoinjection platform allows these cargos to function in the intracellular space as desired. The adaptability of nanoinjection platforms is now bringing major advantages in immunomodulation, mechanotransduction, sampling of cell states (nanobiopsy), controlled intracellular interrogation, and the primary focus of this account─intracellular delivery and its applications in ex vivo cell engineering.

Mechanical nanoinjection typically exerts direct mechanical force on the cell membrane, offering a straightforward route to improve membrane perturbation by the NNs and subsequent transport of genetic cargo into targeted cell type (adherent or suspension cells). By contrast, electroactive nanoinjection is controlled by coupling NNs with an electric field─a new route for activating electroporation (EP) at the nanoscale─allowing a dramatic reduction of the applied voltage to a cell and so minimizing post-EP damage to cells and cargo, and overcoming many of the limitations of conventional bulk EP. Nanoinjection transcends mere technique; it is an approach to cell engineering ex vivo, offering the potential to endow cells with new, powerful features such as generating chimeric antigen receptor (CAR)-T cells for future CAR-T cell technologies.

We first discuss the manufacturing of NN devices (Section 2), then delve into nanoinjection-mediated cell engineering (Section 3), nanoinjection mechanisms an

Neural interface technologies enable bidirectional communication between the nervous system and external instrumentation. Advancements in neural interface devices not only open new frontiers for neuroscience research, but also hold great promise for clinical diagnosis, therapy, and rehabilitation for various neurological disorders. However, the performance of current neural electrode devices, often termed neural probes, is far from satisfactory. Glial scarring, neuronal degeneration, and electrode degradation eventually cause the devices to lose their connection with the brain. To improve the chronic performance of neural probes, efforts need to be made on two fronts: enhancing the physiochemical properties of the electrode materials and mitigating the undesired host tissue response.

In this Account, we discuss our efforts in developing silica-nanoparticle-based (SiNP) coatings aimed at enhancing neural probe electrochemical properties and promoting device–tissue integration. Our work focuses on three approaches:

(1) SiNPs’ surface texturization to enhance biomimetic protein coatings for promoting neural integration. Through covalent immobilization, SiNP introduces biologically relevant nanotopography to neural probe surfaces, enhancing neuronal cell attachments and inhibiting microglia. The SiNP base coating further increases the binding density and stability of bioactive molecules such as L1CAM and facilitates the widespread dissemination of biomimetic coatings. (2) Doping SiNPs into conductive polymer electrode coatings improves the electrochemical properties and stability. As neural interface devices are moving to subcellular sizes to escape the immune response and high electrode site density to increase spatial resolution, the electrode sites need to be very small. The smaller electrode size comes at the cost of a high electrode impedance, elevated thermal noise, and insufficient charge injection capacity. Electrochemically deposited conductive polymer films reduce electrode impedance but do not endure prolonged electrical cycling. When incorporated into conductive polymer coatings as a dopant, the SiNP provides structural support for the polymer thin films, significantly increasing their stability and durability. Low interfacial impedance maintained by the conducting polymer/SiNP composite is critical for extended electrode longevity and effective charge injection in chronic neural stimulation applications. (3) Porous nanoparticles are used as drug carriers in conductive polymer coatings for local drug/neurochemical delivery. When triggered by external electrical stimuli, drug molecules and neurochemicals can be released in a controlled manner. Such precise focal manipulation of cellular and vascular behavior enables us to probe brain circuitry and develop therapeutic applications.

We foresee tremendous opportunities for further advancing the functionality of SiNP coatings by incorporating new nanoscale componen

Aqueous-phase free radicals such as reactive oxygen, halogen, and nitrogen species play important roles in the fate of organic compounds in the aqueous-phase advanced water treatment processes and natural aquatic environments under sunlight irradiation. Predicting the fate of organic compounds in aqueous-phase advanced water treatment processes and natural aquatic environments necessitates understanding the kinetics and reaction mechanisms of initial reactions of free radicals with structurally diverse organic compounds and other reactions. Researchers developed conventional predictive models based on experimentally measured transformation products and determined reaction rate constants by fitting with the time-dependent concentration profiles of species due to difficulties in their measurements of unstable intermediates. However, the empirical treatment of lumped reaction mechanisms had a model prediction limitation with respect to the specific parent compound’s fate. We use ab initio and density functional theory quantum chemical computations, numerical solutions of ordinary differential equations, and validation of the outcomes of the model with experiments. Sensitivity analysis of reaction rate constants and concentration profiles enables us to identify an important elementary reaction in formating the transformation product. Such predictive elementary reaction-based kinetics models can be used to screen organic compounds in water and predict their potentially toxic transformation products for a specific experimental investigation.

Over the past decade, we determined linear free energy relationships (LFERs) that bridge the kinetic and thermochemical properties of reactive oxygen species such as hydroxyl radicals (HO^•), peroxyl radicals (ROO^•), and singlet oxygen (¹O₂); reactive halogen species such as chlorine radicals (Cl^•) and bromine radicals (Br^•); reactive nitrogen species (NO₂^•); and carbonate radicals (CO₃^•–). We used literature-reported experimental rate constants as kinetic information. We considered the theoretically calculated aqueous-phase free energy of activation or reaction to be a kinetic or a thermochemical property, and obtained via validated ab initio or density functional theory-based quantum chemical computations using explicit and implicit solvation models. We determined rate-determining reaction mechanisms involved in reactions by observing robust LFERs. The general accuracy of LFERs to predict aqueous-phase rate constants was within a difference of a factor of 2–5 from experimental values.

We developed elementary reaction-based kinetic models and predicted the fate of acetone induced by HO^• in an advanced water treatment process and methionine by photochemically produced reactive intermediates in sunlit fresh waters. We provided mechanistic insight into peroxyl radical

Facilitated by the unique triple-helical protein structure, fibrous collagens, the principal proteins in animals, demonstrate a dual function of serving as building blocks for tissue scaffolds and as a bioactive material capable of swift renewal in response to environmental changes. While studies of triple-helical collagen mimetic peptides (CMPs) have been instrumental in understanding the molecular forces responsible for the folding and assembly of triple helices, as well as identifying bioactive regions of fibrous collagen molecules, single-strand CMPs that can specifically target and hybridize to denatured collagens (i.e., collagen hybridizing peptides, CHPs) have proven useful in identifying the remodeling activity of collagen-rich tissues related to development, homeostasis, and pathology. Efforts to improve the utility of CHPs have resulted in the development of new skeletal structures, such as dimeric and cyclic CHPs, as well as the incorporation of artificial amino acids, including fluorinated proline and N-substituted glycines (peptoid residues). In particular, dimeric CHPs were used to capture collagen fragments from biological fluid for biomarker study, and the introduction of peptoid-based collagen mimetics has sparked renewed interest in peptidomimetic research because peptoids enable a stable triple-helical structure and the presentation of an extensive array of side chain structures offering a versatile platform for the development of new collagen mimetics.

This Account will cover the evolution of our research from CMPs as biomaterials to ongoing efforts in developing triple-helical peptides with practical theranostic potential in targeting denatured and damaged collagens. Our early efforts in functionalizing natural collagen scaffolds via noncovalent modifications led to the discovery of an entirely new use of CMPs. This discovery resulted in the development of CHPs that are now used by many different laboratories for the investigation of pathologies associated with changes in the structures of extracellular matrices including fibrosis, cancer, and mechanical damage to collagen-rich, load-bearing tissues. Here, we delve into the essential design features of CHPs contributing to their collagen binding properties and practical usage and explore the necessity for further mechanistic understanding of not only the binding processes (e.g., binding domain and stoichiometry of the hybridized complex) but also the biology of collagen degradation, from proteolytic digestion of fibrils to cellular processing of collagen fragments. We also discuss the strengths and weaknesses of peptoid-based triple-helical peptides as applied to collagen hybridization touching on thermodynamic and kinetic aspects of triple-helical folding. Finally, we highlight current limitations and future directions in the use of peptoid building blocks to develop bioactive collagen mimetics as new functional biomaterials.

Intracellular cargo trafficking is a highly regulated process responsible for transporting vital cellular components to their designated destinations. This intricate journey has been a central focus of cellular biology for many years. Early investigations leaned heavily on biochemical and genetic approaches, offering valuable insight into molecular mechanisms of cellular trafficking. However, while informative, these methods lack the capacity to capture the dynamic nature of intracellular trafficking. The advent of fluorescent protein tagging techniques transformed our ability to monitor the complete lifecycle of intracellular cargos, advancing our understanding. Yet, a central question remains: How do these cargos manage to navigate through traffic challenges, such as congestion, within the crowded cellular environment? Fluorescence-based imaging, though valuable, has inherent limitations when it comes to addressing the aforementioned question. It is prone to photobleaching, making long-term live-cell imaging challenging. Furthermore, they render unlabeled cellular constituents invisible, thereby missing critical environmental information. Notably, the unlabeled majority likely exerts a significant influence on the observed behavior of labeled molecules. These considerations underscore the necessity of developing complementary label-free imaging methods to overcome the limitations of fluorescence imaging or to integrate them synergistically.

In this Account, we outline how label-free interference-based imaging has the potential to revolutionize the study of intracellular traffic by offering unprecedented levels of detail. We begin with a brief introduction to our previous findings in live-cell research enabled by interferometric scattering (iSCAT) microscopy, showcasing its aptitude and adeptness in elucidating intricate nanoscale intracellular structures. As we delved deeper into our exploration, we succeeded in the label-free visualization of the entire lifespan of nanoscale protein complexes known as nascent adhesions (NAs) and the dynamic events associated with adhesions within living cells. Our continuous efforts have led to the development of Dynamic Scattering-particle Localization Interference Microscopy (DySLIM), a generalized concept of cargo-localization iSCAT (CL-iSCAT). This label-free, high-speed imaging method, armed with iSCAT detection sensitivity, empowers us to capture quantitative and biophysical insights into cargo transport, providing a realistic view of the intricate nanoscale logistics occurring within living cells. Our in vivo studies demonstrate that intracellular cargos regularly contend with substantial traffic within the crowded cellular environment. Simultaneously, they employ inherent strategies for efficient cargo transport, such as collective migration and hitchhiking, to enhance overall transport rates─intriguingly paralleling the principle and practice of urban traffic management. We also high

Radiation cancer therapies use different ionizing radiation qualities that damage DNA molecules in tumor cells by a yet not completely understood plethora of mechanisms and processes. While the direct action of the radiation is significant, the byproducts of the water radiolysis, mainly secondary low-energy electrons (LEEs, <20 eV) and reactive oxygen species (ROS), can also efficiently cause DNA damage, in terms of DNA strand breakage or DNA interstrand cross-linking. As a result, these types of DNA damage evolve into mutations hindering DNA replication, leading to cancer cell death. Concomitant chemo-radiotherapy explores the addition of radiosensitizing therapeutics commonly targeting DNA, such as platinum derivatives and halogenated nucleosides, to enhance the harmful effects of ionizing radiation on the DNA molecule. Further complicating the landscape of DNA damage are secondary structures such as G-quadruplexes occurring in telomeric DNA. These structures protect DNA from radiation damage, rendering them as promising targets for new and more selective cancer radiation treatments, rather than targeting linear DNA. However, despite extensive research, there is no single paradigm approach to understanding the mysterious way in which ionizing radiation causes DNA damage. This is due to the multidisciplinary nature of the field of research, which deals with multiple levels of biological organization, from the molecular building blocks of life toward cells and organisms, as well as with complex multiscale radiation-induced effects. Also, intrinsic DNA features, such as DNA topology and specific oligonucleotide sequences, strongly influence its response to damage from ionizing radiation. In this Account, we present our studies focused on the absolute quantification of photon- and low-energy electron-induced DNA damage in strategically selected target DNA sequences. Our methodology involves using DNA origami nanostructures, specifically the Rothemund triangle, as a platform to expose DNA sequences to either low-energy electrons or vacuum-ultraviolet (VUV, <15 eV) photons and subsequent atomic force microscopy (AFM) analysis. Through this approach, the effects of the DNA sequence, incorporation of halogenated radiosensitizers, DNA topology, and the radiation quality on radiation-induced DNA strand breakage have been systematically assessed and correlated with fundamental photon- and electron-driven mechanisms underlying DNA radiation damage. At lower energies, these mechanisms include dissociative electron attachment (DEA), where electrons attach to DNA molecules causing strand breaks, and dissociative photoexcitation of DNA. Additionally, further dissociative processes such as photoionization and electron impact contribute to the complex cascade of DNA damage events induced by ionizing radiation. We expect that emerging DNA origami-based approaches will lead to a paradigm shift in research fields associated with DNA damage and suggest fut