Accounts of Chemical Research最新文献

Mechanically interlocked polymers (MIPs) such as polyrotaxanes and polycatenanes are polymer architectures that incorporate mechanical bonds, which represent a compelling frontier in polymer science. MIPs with cross-linked structures are known as mechanically interlocked networks (MINs) and are widely utilized in materials science. Leveraging the motion of mechanical bonds, MINs hold the potential for achieving a combination of robustness and dynamicity. Currently, the reported MINs predominantly consist of networks with discrete mechanical bonds as cross-linking points, exemplified by well-known slide-ring materials and rotaxane/catenane cross-linked polymers. The motion of these mechanically interlocked cross-linking points facilitates the redistribution of tension throughout the network, effectively preventing stress concentration and thereby enhancing material toughness. In these instances, the impact of mechanical bonds can be likened to the adage “small things can make a big difference”, whereby a limited number of mechanical bonds substantially elevate the mechanical performance of conventional polymers. In addition to MINs cross-linked by mechanical bonds, there is another type of MIN in which their principal parts are polymer chains composed of dense mechanical bonds. Within these MINs, mechanical bonds generally serve as repeating units, and their unique properties stem from integrating and amplifying the function of a large amount of mechanical bonds. Consequently, MINs with dense mechanical bonds tend to reflect the intrinsic properties of mechanical interlocked polymers, making their exploration critical for a comprehensive understanding of MIPs. Nevertheless, investigations into MINs featuring dense mechanical bonds remain relatively scarce.

This Account presents a comprehensive overview of our investigation and insights into MINs featuring dense mechanical bonds. First, we delve into the synthetic strategies employed to effectively prepare MINs with dense mechanical bonds, while critically evaluating their advantages and limitations. Through meticulous control of the core interlocking step, three distinct strategies have emerged: mechanical interlocking followed by polymerization, supramolecular polymerization followed by mechanical interlocking, and dynamic interlocking. Furthermore, we underscore the structure–property relationships of MINs with dense mechanical bonds. The macroscopic properties of MINs originate from integrating and amplifying countless microscopic motions of mechanical bonds, a phenomenon we define as an integration and amplification mechanism. Our investigation has revealed detailed motion characteristics of mechanical bonds in bulk mechanically interlocked materials, encompassing the quantification of motion activation energy, discrimination of varying motion distances, and elucidation of the recovery process. Additionally, we have elucidated their influence on the mechanical performance of the res

The ubiquity of sulfur–metal connections in nature inspires the design of bi- and multimetallic systems in synthetic inorganic chemistry. Common motifs for biocatalysts developed in evolutionary biology include the placement of metals in close proximity with flexible sulfur bridges as well as the presence of π-acidic/delocalizing ligands. This Account will delve into the development of a (NO)Fe(N₂S₂) metallodithiolate ligand that harnesses these principles. The Fe(NO) unit is the centroid of a N₂S₂ donor field, which as a whole is capable of serving as a redox-active, bidentate S-donor ligand. Its paramagnetism as well as the ν(NO) vibrational monitor can be exploited in the development of new classes of heterobimetallic complexes. We offer four examples in which the unpaired electron on the {Fe(NO)}⁷ unit is spin-paired with adjacent paramagnets in proximal and distal positions.

First, the exceptional stability of the (NO)Fe(N₂S₂)-Fe(NO)₂ platform, which permits its isolation and structural characterization at three distinct redox levels, is linked to the charge delocalization occurring on both the Fe(NO) and the Fe(NO)₂ supports. This accommodates the formation of a rare nonheme {Fe(NO)}⁸ triplet state, with a linear configuration. A subsequent FeNi complex, featuring redox-active ligands on both metals (NO on iron and dithiolene on nickel), displayed unexpected physical properties. Our research showed good reversibility in two redox processes, allowing isolation in reduced and oxidized forms. Various spectroscopic and crystallographic analyses confirmed these states, and Mössbauer data supported the redox change at the iron site upon reduction. Oxidation of the complex produced a dimeric dication, revealing an intriguing magnetic behavior. The monomer appears as a spin-coupled diradical between {Fe(NO)}⁷ and the nickel dithiolene monoradical, while dimerization couples the latter radical units via a Ni₂S₂ rhomb. Magnetic data (SQUID) on the dimer dication found a singlet ground state with a thermally accessible triplet state that is responsible for magnetism. A theoretical model built on an H₄ chain explains this unexpected ferromagnetic low-energy triplet state arising from the antiferromagnetic coupling of a four-radical molecular conglomerate. For comparison, two (NO)Fe(N₂S₂) were connected through diamagnetic group 10 cations producing diradical trimetallic complexes. Antiferromagnetic coupling is observed between {Fe(NO)}⁷ units, with exchange coupling constants (J) of −3, −23, and −124 cm^–1 for Ni^II, Pd^II, and Pt^II, respectively. This trend is explained by the enhanced covalency and polarizability of sulfur-dense metallodithiolate ligands. A central paramagnetic trans-Cr(NO)(MeCN) recei

Cancer vaccines have shown tremendous potential in preventing and treating cancer by providing immunogenic antigens to initiate specific tumor immune responses. An in situ vaccine prepared from an autologous tumor can mobilize a patient’s own tumor cell lysate as a reservoir of specific antigens, thus triggering a broad immune response and diverse antitumor immunity in an individually tailored manner. Its efficacy is much better than that of conventional vaccines with a limited number of epitopes. Several conventional therapies, including radiotherapy (RT), chemotherapeutics, photodynamic therapy (PDT), and photothermal therapy (PTT) can activate an anticancer in situ vaccine response by inducing immunogenic cell death (ICD), triggering the exposure of tumor-associated antigens (TAAs), cancerous testis antigens, neoantigens, and danger-associated molecular patterns (DAMPs) with low cost. However, the immunogenicity of dying tumor cells is low, making released antigens and DAMPs insufficient to initiate a robust immune response against malignant cancer. Moreover, the immunosuppressive tumor microenvironment (TME) severely hinders the infiltration and sensitization of effector immune cells, causing tolerogenic immunological effects.

Herein, we mainly focus on the research in developing nanoplatforms to surmount the major challenges met by ICD-based in situ vaccines. We first summarized a variety of nanotechnologies that enable enhanced immunogenicity of dying cancer cells by enhancing antigenicity and adjuvanticity. The robust antigenicity was obtained via regulating the tumor cells death mode or the dying state to amplify the recognition of tumor debris by professional antigen-presenting cells (APCs). The adjuvanticity was potentiated by raising the level or intensifying the activity of endogenous adjuvants or promoting the intelligent delivery of exogenous immunostimulants to activate immune cell recruitment and promote antigen presentation. Additionally, versatile approaches to reverse immunosuppressive TME to boost the in situ tumor vaccination response are also highlighted in detail. On one hand, by modulating the cell metabolism in TME, the expansion and activity of effector versus immunosuppressive cells can be optimized to improve the efficiency of in situ vaccines. On the other hand, regulating cellular components in TME, such as reversing adverse immune cell phenotypes or inhibiting the activity of interstitial cells, can also significantly enhance the ICD-based antitumor immunotherapy effect. Finally, our viewpoint on the future challenges and opportunities in this hopeful area is presented. We expect that this Account can offer much more insight into the design, planning, and development of cutting-edge in situ tumor vaccine platforms, promoting more attention and academic–industry collaborations, accelerating the advanced progress of in situ tumor vaccine-based immunotherapy i

An understanding of the mechanistic processes that underpin reactions catalyzed by 3d transition metals is vital for their development as potential replacements for scarce platinum group metals. However, this is a significant challenge because of the tendency of 3d metals to undergo mechanistically diverse pathways when compared with their heavier congeners, often as a consequence of one-electron transfer reactions and/or intrinsically weaker metal–ligand bonds. We have developed and implemented a new methodology to illuminate the pathways that underpin C–H bond functionalization pathways in reactions catalyzed by Mn–carbonyl compounds. By integrating measurements performed on catalytic reactions with in situ reaction monitoring and state-of-the-art ultrafast spectroscopic methods, unique insight into the mode of action and fate of the catalyst have been obtained.

Using a combination of time-resolved spectroscopy and in situ low-temperature NMR studies, we have shown that photolysis of manganese–carbonyl precatalysts results in rapid (<5 ps) CO dissociation─the same process that occurs under thermal catalytic conditions. This enabled the detection of the key states relevant to catalysis, including solvent and alkyne complexes and their resulting transformation into manganacycles, which results from a migratory insertion reaction into the Mn–C bond. By systematic variation of the substrates (many of which are real-world structurally diverse substrates and not simple benchmark systems) and quantification of the resulting rate constants for the insertion step, a universal model for this migratory insertion process has been developed. The time-resolved spectroscopic method gave insight into fundamental mechanistic pathways underpinning other aspects of modern synthetic chemistry. The most notable was the first direct experimental observation of the concerted metalation deprotonation (CMD) mechanism through which carboxylate groups are able to mediate C–H bond activation at a metal center. This step underpins a host of important synthetic applications. This study demonstrated how the time-resolved multiple probe spectroscopy (TR^MPS) method enables the observation of mechanistic process occurring on time scales from several picoseconds through to μs in a single experiment, thereby allowing the sequential observation of solvation, ligand substitution, migratory insertion, and ultimate protonation of a Mn–C bond.

These studies have been complemented by an investigation of the “in reaction flask” catalyst behavior, which has provided additional insight into new pathways for precatalyst activation, including evidence that alkyne C–H bond activation may occur before heterocycle activation. Crucial insight into the fate of the catalyst species showed that excess water played a key role in deactivation to give higher-order hydroxyl-bridged manganese carbonyl clusters, which were independently found to be inactive. Traditional i

The intrinsic molecular order of liquid crystals (LCs) and liquid crystalline elastomers (LCEs) is the origin of their stimuli-responsive properties. The programmable responsiveness and functionality, such as shape morphing and color change under external stimuli, are the key features that attract interest in designing LC- and LCE-based intelligent material platforms. Methods such as mechanical stretching and shearing, surface alignment, and field-assisted alignment have been exploited to program the order of LC molecules for the desired responsiveness. However, the huge size mismatch between the nanometer-sized LC mesogens and the targeted macroscopic objects calls for questions about how to delicately control molecular order for desired performance. Microparticles that can be synthesized with intrinsic molecular order precisely controlled to micrometer size can be used as building blocks for bulk materials, thus offering opportunities to bridge the gap and transcend molecular orders across scales. By taking advantage of the interfacial anchoring effects, we can control and engineer the molecular orders inside the microdroplets, allowing for the realization of various responsive behaviors. Furthermore, designer LC microparticles with multiple responsiveness can be assembled and confined within a matrix, opening a new pathway to engineering LC-enabled intelligent materials.

In this Account, we present our recent work on exploiting the molecular order inside microdroplets for the construction of intelligent materials. We briefly introduce the typical chemicals used in the synthesis and the methods developed to control LC molecular alignment within a microdroplets. We then present examples of microparticles synthesized from microdroplets that can transform into complex morphologies upon cooling from the isotropic to nematic phase or due to phase separation within the droplets coupled with the segregation of LC oligomers (LCOs) with polydisperse chain lengths. Furthermore, we show the synthesis of elliptical LCE microparticles and exploit their thermal and magnetic responsiveness to program shape-morphing behaviors and microarrays with switchable optical polarization. By mixing magnetic nanoparticles in cholesteric liquid crystals (CLCs) and silicone oils, we created Janus microparticles capable of color switching for camouflage and information encryption. Moreover, we can engineer complex molecular orders in LCE microparticles by mixing different surfactants, yielding microparticles of diverse anisotropic, temperature-responsive shapes after photopolymerization and extraction of the template LC molecules with different solvents. We conclude the Account with an outlook on the design of intelligent material systems via the design of unprecedented molecular ordering within the microparticles and their coupling with bulk materials.

The selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which is important for the development of medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing to thermodynamic stability, kinetic inertness, and lone electron pair–induced catalyst deactivation of the pyridine-fused N-heteroarenes, limited strategies (e.g., C–H activation/functionalization, electrophilic substitution, and the Minisci reaction) are available to realize the synthetic purpose and maintain the aromaticity of the final products. Moreover, the relevant transformations have limitations such as needing harsh reaction conditions, requiring the preinstallation of specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, and poor selectivity. Herein, considering that imines, enamines, radicals, and cyclic amines are generated during the reduction of pyridine-fused N-heteroarenes, the precise transformation of these reductive intermediates offers a fundamental basis for developing novel tandem reactions. Our group revealed that a slow reduction rate, synergistic catalysis, and controlled electroreduction are effective strategies for fulfilling the selective reductive functionalization of pyridine-fused N-heteroarenes. Thus, we established a series of new synthetic methods that provide diverse construction modalities for functionalized N-heterocycles. The striking features of these synthetic methods include high efficiency, atom economy, and the use of readily accessible N-heteroarenes as transformable feedstocks in the absence of flammable and pressurized H₂ gas, alongside a promising potential of the obtained N-heterocyclic products. The present study would be appealing to the fields of synthetic organic chemistry, catalysis, biomedical chemistry, and functional materials. This Account describes the application of reductive dearomatization as substrate-activating and tandem reaction-initiating modes and summarizes the reductive functionalization of pyridine-fused N-heteroarenes via selective alkylation, arylation, and annulation at nitrogen, α, β, and other remote carbon sites achieved over the past 8 years. Details regarding the development of new reactions and their plausible mechanisms and perspectives are discussed. We hope our contributions to this field will aid in the further development of novel strategies for the functionalization/transformation of pyridine-fused N-heteroarenes and tackle the intractable challenges in this area.

Biologically active compounds and pharmaceutically relevant intermediates often feature sterically congested stereogenic centers, in particular, carbon stereocenters that are either tertiary tetrasubstituted ones or quaternary in nature. Synthons that comprise such bulky and often structurally complex core units are of high synthetic value and represent important incentives for communities connected to drug discovery and development. Streamlined approaches that give access to a diverse set of compounds incorporating acyclic bulky stereocenters are relatively limited, though vital. They enable further exploration of three-dimensional entities that can be designed and implemented in discovery programs, thereby extending the pool of molecular properties that is inaccessible for flat molecules. However, the lack of modular substrates in particular areas of chemical space inspired us to consider functionalized heterocycles known as cyclic carbonates and carbamates as a productive way to create sterically crowded alkenes and stereocenters.

In this Account, we describe the major approximations we followed over the course of 8 years using transition metal (TM) catalysis as an instrument to control the stereochemical course of various allylic and propargylic substitution processes and related transformations. Allylic substitution reactions empowered by Pd-catalysis utilizing a variety of nucleophiles are discussed, with amination being the seed of all of this combined work. These procedures build on vinyl-substituted cyclic carbonates (VCCs) that are simple and easy-to-access precursors and highly modular in nature compared to synthetically limited vinyl oxiranes. Overall these decarboxylative conversions take place with either “linear” or “branched” regioselectivities that are ligand controlled and offer access to a wide scope of functional allylic scaffolds. Alternative approaches, including dual TM/photocatalyzed transformations, allowed us to expand the repertoire of challenging stereoselective conversions. This was achieved through key single-electron pathways and via formal umpolung of intermediates, resulting in new types of carbon–carbon bond formation reactions significantly expanding the scope of allylic substitution reactions.

Heterocyclic substrate variants that have triple bond functional groups were also designed by us to enable difficult-to-promote stereoselective propargylic substitution reactions through TM catalysis. In these processes, inspired by the Nishibayashi laboratory and their seminal findings in the area, we discovered various new reactivity patterns. This provided access to a range of different stereodefined building blocks such as 1,2-diborylated 1,3-dienes and tetrasubstituted α-allenols under Cu- or Ni-catalysis. In this realm, the use of lactone-derived substrates gives access to elusive chiral γ-amino acids and lactams with high stereofidelity and good structural diversity.

Apart from the syntheti

Polycyclic (hetero)aromatic hydrocarbons (PAHs) have emerged as a focal point in current interdisciplinary research, spanning the realms of chemistry, physics, and materials science. Possessing distinctive optical, electronic, and magnetic properties, these π-functional materials exhibit significant potential across diverse applications, including molecular electronic devices, organic spintronics, and biomedical functions, among others. Despite the extensive documentation of various PAHs over the decades, the efficient and precise synthesis of π-extended PAHs remains a formidable challenge, hindering their broader application. This challenge is primarily attributed to the intricate and often elusive nature of their synthesis, compounded by issues related to low solubility and unfavored stability.

The development of π-building blocks that can be facilely and modularly transformed into diverse π-frameworks constitutes a potent strategy for the creation of novel PAH materials. For instance, based on the classic perylene diimide (PDI) unit, researchers such as Würthner, Wang, and Nuckolls have successfully synthesized a plethora of structurally diverse PAHs, as well as numerous other π-functional materials. However, until now the availability of such versatile building blocks is still severely limited, especially for those simultaneously having a facile preparation process, adequate solubilizing groups, favored material stability, and critically, rich possibilities for structural extension spaces.

In this Account, we present an overview of our invention of a highly versatile bay-/ortho-octa-substituted perylene building block, designated as Per-4Br, for the construction of a series of novel PAH scaffolds with tailor-made structures and rich optoelectronic and magnetic properties. First, starting with a brief discussion of current challenges associated with the bottom-up synthesis of π-extended PAHs, we rationalize the key features of Per-4Br that enable facile access to new PAH molecules including its ease of large-scale preparation, favored material stability and solubility, and multiple flexible reaction sites, with a comparison to the PDI motif. Then, we showcase our rational design and sophisticated synthesis of a body of neutral or charged, closed- or open-shell, curved, or planar PAHs via controlled annulative π-extensions in different directions such as peripheral, diagonal, or multiple dimensions of the Per-4Br skeleton. In this part, the fundamental structure–property relationships between molecular conformations, electronic structures, and self-assembly behaviors of these PAHs and their unique physiochemical properties such as unusual open-shell ground states, global aromaticity, state-associated/stimuli-responsive magnetic activity, and charge transport characteristics will be emphatically elaborated. Finally, we offer our perspective on the continued advancement of π-functional material

The development of catalytic activation modes provides a reliable and effective platform for designing new enantioselective reactions and preparing chiral molecules with diverse structures. Chiral aldehyde catalysis is an attractive concept in asymmetric catalysis, which utilizes a chiral aldehyde catalyst to promote the asymmetric hydroamination of allylic amines, the asymmetric α-functionalization of primary amines, or the asymmetric transamination of α-keto esters. Typically, the chiral aldehyde-catalyzed asymmetric α-functionalization of primary amines provides an efficient and straightforward method for the synthesis of α-functionalized chiral amines, which does not require any additional protection or deprotection manipulations of the amine group. However, achieving catalytic stereoselective transformations with high efficiency and enantioselectivity by this strategy has remained an intractable challenge.

This Account summarizes our endeavors in the development and application of chiral aldehyde catalysis. Using a chiral aldehyde as a catalyst, we reported the catalytic asymmetric α-C alkylation of 2-aminomalonate with 3-indolylmethanol in 2014, which represents the first chiral aldehyde-catalyzed asymmetric α-functionalization of an activated primary amine. Subsequently, several axially chiral aldehyde catalysts were continuously prepared by using chiral BINOL as the starting material, and their applications in asymmetric synthesis were explored. On the one hand, they were used as organocatalysts to realize the various transformations of α-amino acid esters, such as asymmetric 1,4-addition toward conjugated enones/α,β-unsaturated diesters and cyclic 1-azadienes as well as asymmetric α-arylation/allylation and benzylation with corresponding halohydrocarbons. Notably, taking advantage of the difference in the distribution of catalytic sites between two chiral aldehyde catalysts, we disclosed chiral aldehyde-catalyzed diastereodivergent 1,6-conjugated addition and Mannich reactions. On the other hand, the potential for the cooperative catalysis of a chiral aldehyde with a transition metal has also been demonstrated. Enabled by the combination of a chiral aldehyde, a palladium complex, and a Lewis acid, the enantioselective α-allylation of amino acid esters with allyl alcohol esters was established. Moreover, the ternary catalytic system has been successfully used for the α-functionalization of amino acid esters with 1,3-dienes, allenes, allenylic alcohol esters, 1,3-disubstituted allyl alcohol esters, and arylmethanol esters as well as the asymmetric cascade Heck-alkylation reaction. The combination of a chiral aldehyde and nickel complex allows for the asymmetric α-propargylation of amino acid esters with propargylic alcohol esters and provides excellent enantioselectivities. These transformations provide a large library of optically active amines and amino acids. With those chiral amino acid esters as key building blocks, the syn

Molecular polyhedral cages, notable for their enclosed inner cavities, can possess varying degrees of symmetry, spanning from regular Platonic polyhedra to lower symmetry forms that may display chirality. Crafting chiral molecular cages typically involves using building blocks containing stereogenic elements or arranging achiral components in a manner that lacks mirror and inversion symmetries. Achieving precise control over their chirality poses both significance and challenges.

In this Account, we present an overview of our research endeavors in the realm of chiral molecular polyhedral cages, drawing inspiration from Buckminster Fuller’s “Face-Rotating Polyhedra (FRP)”. Mathematically, FRP introduce a unique form of chirality distinguished by a rotating pattern around the center of each face, setting it apart from regular polyhedra.

Molecular FRP can be constructed using two types of facial building blocks. The first includes rigid, planar molecules such as truxene and triazatruxene, which exhibit either clockwise or counterclockwise rotations in two dimensions. The second category involves propeller-like molecules, e.g., tetraphenylethylene, 1,2,3,4,5-penta(4-phenylaldehyde)pyrrole, and tridurylborane, displaying dynamic stereochemistry.

The synthesis of FRP may potentially yield a diverse array of stereoisomers. Achieving high stereoselectivity becomes feasible through the selection of building blocks with specific substitution patterns and rigidity. Prominent noncovalent repulsive forces within the resulting cages often play a pivotal role in the dynamic covalent assembly process, ultimately leading to the formation of thermodynamically stable FRP products.

The capacity to generate a multitude of stereoisomers, combined with the integration of chiral vertices, has facilitated investigations into phenomena such as chiral self-sorting and the “sergeant and soldiers” chiral amplification effect in FRP. Even the inclusion of one chiral vertex significantly impacts the stereochemical configuration of the entire cage. While many facial building blocks establish a stable rotational pattern in FRP, other units, such as tridurylborane, can dynamically transition between P and M configurations within the cage structures. The kinetic characteristics of such stereolabile FRP can be elucidated through physicochemical investigations.

Our research extends beyond the FRP concept to encompass mathematical analysis of these structures. Graph theory, particularly the coloring problem, sheds light on the intricate facial patterns exhibited by various FRP stereoisomers and serves as an efficient tool to facilitate the discovery of novel FRP structures. This approach offers a fresh paradigm for designing and analyzing chiral molecular polyhedral cages, showcasing in our work the synergy between mathematics and molecular design.