Showing papers in "Accounts of Chemical Research in 2022"

Metalloporphyrins as Catalytic Models for Studying Hydrogen and Oxygen Evolution and Oxygen Reduction Reactions.

Abstract: ConspectusThe hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) are involved in biological and artificial energy conversions. H-H and O-O bond formation/cleavage are essential steps in these reactions. In nature, intermediates involved in the H-H and O-O bond formation/cleavage are highly reactive and short-lived, making their identification and investigation difficult. In artificial catalysis, the realization of these reactions at considerable rates and close to their thermodynamic reaction equilibria remains a challenge. Therefore, the elucidation of the reaction mechanisms and structure-function relationships is of fundamental significance to understand these reactions and to develop catalysts.This Account describes our recent investigations on catalytic HER, OER, and ORR with metalloporphyrins and derivatives. Metalloporphyrins are used in nature for light harvesting, energy conversion, electron transfer, O2 activation, and peroxide degradation. Synthetic metal porphyrin complexes are shown to be active for these reactions. We focused on exploring metalloporphyrins to study reaction mechanisms and structure-function relationships because they have stable and tunable structures and characteristic spectroscopic properties.For HER, we identified three H-H bond formation mechanisms and established the correlation between these processes and metal hydride electronic structures. Importantly, we provided direct experimental evidence for the bimetallic homolytic H-H bond formation mechanism by using sterically bulky porphyrins. Homolytic HER has been long proposed but rarely verified because the coupling of active hydride intermediates occurs spontaneously and quickly, making their detection challenging. By blocking the bimolecular mechanism through steric effects, we stabilized and characterized the NiIII-H intermediate and verified homolytic HER by comparing the reaction behaviors of Ni porphyrins with and without steric effects. We therefore provided an unprecedented example to control homolytic versus heterolytic HER mechanisms through tuning steric effects of molecular catalysts.For the OER, the water nucleophilic attack (WNA) on high-valent terminal Mn-oxo has been proposed for the O-O bond formation in natural and artificial water oxidation. By using Mn tris(pentafluorophenyl)corrole, we identified MnV(O) and MnIV-peroxo intermediates in chemical and electrochemical OER and provided direct experimental evidence for the Mn-based WNA mechanism. Moreover, we demonstrated several catalyst design strategies to enhance the WNA rate, including the pioneering use of protective axial ligands. By studying Cu porphyrins, we proposed a bimolecular coupling mechanism between two metal-hydroxide radicals to form O-O bonds. Note that late-transition metals do not likely form terminal metal-oxo/oxyl.For the ORR, we presented several strategies to improve activity and selectivity, including providing rapid electron transfer, using electron-donating axial ligands, introducing hydrogen-bonding interactions, constructing dinuclear cooperation, and employing porphyrin-support domino catalysis. Importantly, we used Co porphyrin atropisomers to realize both two-electron and four-electron ORR, representing an unparalleled example to control ORR selectivity by tuning only steric effects without modifying molecular and/or electronic structures.Lastly, we developed several strategies to graft metalloporphyrins on various electrode materials through different covalent bonds. The molecular-engineered materials exhibit boosted electrocatalytic performance, highlighting promising applications of molecular electrocatalysis. Taken together, this Account demonstrates the benefits of exploring metalloporphyrins for the HER, OER, and ORR. The knowledge learned herein is valuable for the development of porphyrin-based catalysts and also other molecular and material catalysts for small molecule activation reactions.

Reticular Chemistry for Highly Porous Metal-Organic Frameworks: The Chemistry and Applications.

Abstract: ConspectusCurrent global crises related to clean energy and the environment entail the development of materials that are capable of addressing these challenges. Metal-organic frameworks (MOFs), a class of functional materials assembled from metal-containing nodes and organic ligands via coordination bonds, have been successfully developed for various applications, including catalysis, toxic chemical removal, and gas storage and separation, as a result of their highly tailorable nature and precisely engineered pore structures. In particular, the exceptionally high surface areas and porosities of MOFs are two of their most attractive characteristics and place them among the best porous materials for the storage of clean energy gases, such as hydrogen and methane. Reticular chemistry stands out as a prominent approach to the design of MOFs as this strategy allows for the rational top-down design of frameworks guided by topological nets to afford extended framework structures with precise architectural arrangements at the molecular level. Bridging the gap between reticular chemistry design strategies and highly porous MOFs can facilitate the development of next-generation high-performance materials through state-of-the-art chemical design.In this Account, we summarize our group's efforts over the past few years toward the synthesis and applications of highly porous MOFs inspired by reticular chemistry. First, we describe how we leveraged reticular chemistry to synthesize NU-1500, which is based on the 6-connected edge-transitive acs net, from the assembly of triptycene-based ligands and high-valent metal trimers. This delicate design is amenable to isoreticular expansion, and including an additional phenyl group in the rigid triptycene-based ligand of NU-1500 yields NU-1501. Importantly, NU-1501-Al exhibits both a high gravimetric Brunauer-Emmett-Teller (BET) area of 7310 m2 g-1, which is the current record after satisfying the four BET consistency criteria, and a volumetric BET area of 2060 m2 cm-3. The high porosity and surface area place NU-1501 among the most promising adsorbents for the storage of methane and hydrogen. Second, we illustrate the rational synthesis of highly porous and stable Zr-MOFs based on edge-transitive nets: (1) the successful isoreticular expansions of NU-1000 (a 4,8-connected csq net) form hierarchical mesoporous MOFs with pore sizes of up to 6.7 nm; (2) the assembly of Zr6 clusters and tetracarboxylates yields the NU-1100 series (4,12-connected ftw net) with BET areas of 4300-6500 m2 g-1; and (3) the use of hexacarboxylates in combination with Zr6 clusters results in the formation of the NU-1600 series (a 6,12-connected alb net) with BET areas of 2000-4500 m2 g-1. Third, we leveraged a reticular exploration strategy to access mesoporous uranium-based MOFs, NU-1300 (a 3,4-connected tbo net, 2100 m2 g-1) and NU-1301 (a 3-connected nun net, 4750 m2 g-1). In particular, we investigated the structurally complex NU-1301, which formed serendipitously from the combination of uranyl clusters and triangular carboxylates to afford a structure with the largest unit cell among all reported MOFs.Finally, we provide an overview of potential applications of these highly porous MOFs, including water capture, catalysis, methane storage, hydrogen storage, and the separation of organic dyes and biological macromolecules. We hope that this Account may serve as a blueprint and stimulate researchers to develop the next generation of highly porous materials for energy- and environment-related applications and beyond.

Long-Lived Organic Room-Temperature Phosphorescence from Amorphous Polymer Systems.

Abstract: ConspectusLong-lived organic room-temperature phosphorescence (RTP) materials have recently drawn extensive attention because of their promising applications in information security, biological imaging, optoelectronic devices, and intelligent sensors. In contrast to conventional fluorescence, the RTP phenomenon originates from the slow radiative transition of triplet excitons. Thus, enhancing the intersystem crossing (ISC) rate from the lowest excited singlet state (S1) to the excited triplet state and suppressing the nonradiative relaxation channels of the lowest excited triplet state (T1) are reasonable methods for realizing highly efficient RTP in purely organic materials. Over the past few decades, many strategies have been designed on the basis of the above two crucial factors. The introduction of heavy atoms, aromatic carbonyl groups, and other heteroatoms with abundant lone-pair electrons has been demonstrated to strengthen the spin-orbit coupling, thereby successfully facilitating the ISC process. Furthermore, the rigid environment is commonly constructed through crystal engineering to restrict intramolecular motions and intermolecular collisions to decrease excited-state energy dissipation. However, most crystal-based organic RTP materials suffer from poor processability, flexibility, and reproducibility, becoming a thorny obstacle to their practical application.Amorphous organic polymers with long-lived RTP characteristics are more competitive in materials science. The intertwined structures and long chains of polymers not only ensure the rigid environment with multiple interactions but also protect triplet excitons from the surroundings, which are conducive to realizing ultralong and bright RTP emission. Exploring the fabrication strategies, intrinsic mechanisms, and practical applications of organic long-lived RTP polymers is highly desirable but remains a formidable challenge. In particular, intelligent organic RTP polymer systems that are capable of dynamically responding to external stimuli (e.g., light, temperature, oxygen, and humidity) have been rarely reported. To develop multifunctional RTP materials and expand their potential applications, a great amount of effort has been expended.This Account gives a summary of the significant advances in amorphous organic RTP polymer systems, especially smart stimulus-responsive ones, focusing on the construction of a rigid environment to suppress nonradiative deactivation by abundant inter/intramolecular interactions. The typical interactions in RTP polymer systems mainly include hydrogen bonding, ionic bonding, and covalent bonding, which can change the molecular electronic structures and affect the energy dissipation channels of the excited states. An in-depth understanding of intrinsic mechanisms and an extensive exploration of potential applications for excitation-dependent color-tunable, ultraviolet (UV) irradiation-activated, temperature-dependent, water-responsive, and circularly polarized RTP polymer systems are distinctly illustrated in this Account. Furthermore, we propose some detailed perspectives in terms of materials design, mechanism exploration, and promising application potential with the hope to provide helpful guidance for the future development of amorphous organic RTP polymers.

Selectivity in Electrochemical CO2 Reduction.

Abstract: ConspectusThe electrocatalytic CO2 reduction reaction (CO2RR) to generate fixed forms of carbons that have commercial value is a lucrative avenue to ameliorate the growing concerns about the detrimental effect of CO2 emissions as well as to generate carbon-based feed chemicals, which are generally obtained from the petrochemical industry. The area of electrochemical CO2RR has seen substantial activity in the past decade, and several good catalysts have been reported. While the focus was initially on the rate and overpotential of electrocatalysis, it is gradually shifting toward the more chemically challenging issue of selectivity. CO2 can be partially reduced to produce several C1 products like CO, HCOOH, CH3OH, etc. before its complete 8e-/8H+ reduction to CH4. In addition to that, the low-valent electron-rich metal centers deployed to activate CO2, a Lewis acid, are prone to reduce protons, which are a substrate for CO2RR, leading to competing hydrogen evolution reaction (HER). Similarly, the low-valent metal is prone to oxidation by atmospheric O2 (i.e., it can catalyze the oxygen reduction reaction, ORR), necessitating strictly anaerobic conditions for CO2RR. Not only is the requirement of O2-free reaction conditions impractical, but it also leads to the release of partially reduced O2 species such as O2-, H2O2, etc., which are reactive and result in oxidative degradation of the catalyst.In this Account, mechanistic investigations of CO2RR by detecting and, often, chemically trapping and characterizing reaction intermediates are used to understand the factors that determine the selectivity in CO2RR. The spectroscopic data obtained from different intermediates have been identified in different CO2RR catalysts to develop an electronic structure selectivity relationship that is deemed to be important for deciding the selectivity of 2e-/2H+ CO2RR. The roles played by the spin state, hydrogen bonding, and heterogenization in determining the rate and selectivity of CO2RR (producing only CO, only HCOOH, or only CH4) are discussed using examples of both iron porphyrin and non-heme bioinspired artificial mimics. In addition, strategies are demonstrated where the competition between CO2RR and HER as well as CO2RR and ORR could be skewed overwhelmingly in favor of CO2RR in both cases.

Asymmetric Catalytic Rearrangements with α-Diazocarbonyl Compounds.

Abstract: Conspectusα-Diazocarbonyl compounds serve as nucleophiles, dipoles, carbene precursors, and rare electrophiles, enabling a vast array of organic transformations under the influence of metal catalysts. Among them, rearrangement processes are attractive and provide straightforward and efficient accesses to one-carbon extension adducts or heteroatom-containing molecules. The reactions occur upon the release of dinitrogen after nucleophilic addition or before ylide formation. Although significant progress has been made for these two types of rearrangement reactions, the issue of enantiocontrol is challenging because the final optically enriched products are generated via multistep transformations and the inherent spacial arrangement of the intermediates has more or less influence on the regio- and enantioselectivity.In this Account, we collected several rearrangements of α-diazocarbonyl compounds, showcasing the efficient catalysts and tailored strategies for tackling enantioselective varieties of these two types of rearrangement reactions. Our research group initiated the catalytic asymmetric reactions of α-diazocarbonyl compounds during the development of chiral Feng N,N'-dioxide-metal complex catalysts and others. As a kind of useful chiral Lewis acid catalyst chiral N,N'-dioxide-metal complexes are favorable for the activation of various carbonyl compounds, accelerating the diastereo- and enantioselective nucleophilic addition of α-diazoesters and the sequential rearrangements in either an intermolecular or intramolecular manner. Aldehydes, acyclic and cyclic ketone derivatives, and α,β-unsaturated ketones could participate in efficient asymmetric homologation reactions, and an obvious ligand-acceleration effect is observed in these processes. For example, the Roskamp-Feng reaction of aldehydes gives optically active β-ketoesters through a H-shift, overwhelming the aryl group shift or oxygen attack. The shift preference and enantiocontrol in the homologation of acyclic and cyclic ketone derivatives could be under excellent control of the chiral catalysts. An unusual electrophilic α-amination of aryl/alkyl ketones and even a complicated homologation/dyotropic rearrangement/interconversion/[3 + 2] cycloaddition cascade used to construct dimeric polycyclic compounds were discovered as a result of the selection of chiral ligands and additives. On the basis of the understanding of the interaction of the functional group with N,N'-dioxide-metal complexes in catalysis and the key enantio-determining issues in ylide-based rearrangements, we designed new α-diazocarbonyl compounds by introducing a pyrazole-1-carboxyl group as the acceptor unit, which could benefit the formation of both carbenoid species and the chiral catalyst-bound ylides to deliver stereoselectivity. Taking advantage of Ni(II) or Co(II) complexes of Feng N,N'-dioxide ligands, we realized several kinds of enantioselective [2,3]-sigmatropic rearrangements, such as the Doyle-Kirmse reaction with allylic sulfides or selenides, [2,3]-Stevens rearrangements of vinyl-substituted α-diazo pyrazoleamides with thioacetates, Sommelet-Hauser rearrangements of aryl-substituted α-diazo pyrazoleamides with thioamides, and thio-Claisen rearrangements of 2-thio-indoles as well. Moreover, this strategy was shown to be applicable to highly γ-selective and enantioselective insertion into N-H bonds of secondary amines with vinyl-substituted α-diazo pyrazoleamides.

Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications.

Abstract: ConspectusCatalytic atroposelective syntheses of axially chiral compounds have stimulated extensive interest in multiple communities, such as synthetic chemistry, biochemistry, and materials science, because of the intriguing characteristics of atropisomerism. In particular, atropisomeric indole derivatives, which contain a kind of five-membered heterocyclic framework, are widely distributed in a number of natural alkaloids, biologically relevant compounds, chiral ligands, and chiral organocatalysts. Hence, the catalytic atroposelective synthesis of indole derivatives bearing axial chirality is of considerable importance and has become an emerging focus of research. However, there are substantial challenges associated with the atroposelective synthesis of indole derivatives, including remote ortho-substituents around the chiral axis, a lower barrier for rotation, and a weaker configurational stability than that of atropisomeric six-membered biaryls. Therefore, the development of effective strategies toward the catalytic atroposelective synthesis of indole derivatives has become an urgent task.In order to tackle these challenges and to accomplish the task, our group devised a unique strategy of designing indole-derived platform molecules and developing organocatalytic enantioselective transformations of such platform molecules to synthesize atropisomeric indole derivatives; asymmetric organocatalysis has tremendous advantages and was the research area recognized by the Nobel Prize in Chemistry in 2021. This Account summarizes our endeavors in the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality. In brief, we devised and developed a series of indole-derived platform molecules, such as indolylmethanols, (hetero)aryl indoles, oxindole-based styrenes, N-aminoindoles, and indole-based homophthalic anhydrides, by introducing different functional groups onto the indole ring to achieve new reactivity and modulate the reactive site of the indole ring. As a result, these indole-derived platform molecules possess versatile and unique reactivity and are capable of undergoing a variety of organocatalytic enantioselective transformations for preparing structurally diversified indole derivatives with axial chirality.We used these strategies to accomplish the atroposelective synthesis of plenty of indole derivatives with axial chirality, including (hetero)aryl indoles, alkene-indoles, oxindole-based styrenes, N-pyrrolylindoles, and isochromenone-indoles. In addition, we gave a thorough and detailed understanding of the designed reaction by investigating the reaction pathway and activation mode. More importantly, we studied the biological activity of some products and performed catalyst design on the basis of atropisomeric indole moieties, which are helpful for disclosing more applications of indole derivatives bearing axial chirality.In the future, the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality will indubitably remain a frontier topic in the research area of asymmetric catalysis and chiral indole chemistry despite challenging issues, for instance, the atroposelective synthesis of novel indole derivatives bearing an unconventional chiral axis, the development of atropisomeric indole derivatives into powerful catalysts or ligands, and the discovery of atroposelective indole derivatives as potent drug candidates. We hope our efforts summarized in this Account will encourage chemists worldwide to devise innovative strategies toward solving the challenging issues that remain in this field, thus promoting its development to a higher level.

UV/Chlorine Process: An Efficient Advanced Oxidation Process with Multiple Radicals and Functions in Water Treatment

Abstract: Because of the deterioration of global water quality, the occurrence of chemical and microbial contaminants in water raises serious concerns for the health of the population. Identifying and developing effective and environmentally friendly water treatment technologies are critical to obtain clean water. Among the various technologies for the purification of water, ultraviolet photolysis of chlorine (UV/chlorine), an emerging advanced oxidation process (AOP), has multiple functions for the control of contaminants via the production of hydroxyl radicals (HO·) and reactive chlorine species (RCS), such as Cl·, ClO·, and Cl2·-.This Account centers around the radical chemistry of RCS and HO· in different water matrices and their roles and mechanisms in the abatement of contaminants. The concentrations of Cl·, ClO·, and Cl2·- are comparable to or higher than those of HO· (10-14 to 10-13 M). The reactivities of RCS are more selective than HO· with a broader range of second-order rate constants (k). The k values of Cl· toward most aromatics are higher or similar as compared to those of HO·, while those of Cl2·- and ClO· are less reactive but more selective toward aromatics containing electron-donating functional groups. Their major reaction mechanisms with Cl· are electron transfer and addition, while those with ClO· and Cl2·- primarily involve electron transfer. As for aliphatics, their reactivities with both HO· and RCS are much lower than those of aromatics. The reaction mechanisms for most of them with Cl· and Cl2·- are hydrogen abstraction, except for olefins, which are addition. In addition, RCS greatly contribute to the inactivation of microbial contaminants.Toward future application, the UV/chlorine process has both pros and cons. Compared with the traditional HO·-based AOP of UV/H2O2, UV/chlorine is more efficient and energy-saving for oxidation and disinfection, and its efficiency is less affected by water matrix components. However, the formation of toxic byproducts in UV/chlorine limits its application scenarios. In dissolved organic matter (DOM)-rich water, the formation of halogenated byproducts is enhanced in UV/chlorine. In the presence of ammonia, reactive nitrogen species (RNS) (e.g., ·NO and ·NO2) are involved, and highly toxic nitro(so) products such as nitro(so)-phenolics and N-nitrosodimethylamine are generated. For a niche application, the UV/chlorine process is recommended to be utilized in water with low levels of DOM and ammonia.Strategies should be developed to make full use of highly reactive species (RCS and HO·) for the abatement of target contaminants and to reduce the formation of toxic byproducts. For example, the UV/chlorine process can be used in tandem with other treatments to create multiple barriers for the production of safe water. In addition, halogen radicals are very important in ecosystems as well as other areas such as medical therapy and organic synthesis. UV/chlorine is the most efficient homogeneous system to generate halogen radicals, and thus it provides a perfect system to investigate the fates of halogen radicals for interdisciplinary research.

Electrochemical Approaches for CO2 Conversion to Chemicals: A Journey toward Practical Applications.

Abstract: ConspectusCarbon capture, utilization, and sequestration play an essential role to address CO2 emissions. Among all carbon utilization technologies, CO2 electroreduction has gained immense interest due to its potential for directly converting CO2 to a variety of valuable commodity chemicals using clean, renewable electricity as the sole energy source. The research community has witnessed rapid advances in CO2 electrolysis technology in recent years, including highly selective catalysts, larger-scale reactors, specific process modeling, as well as a mechanistic understanding of the CO2 reduction reaction. The rapid advances in the field brings promise to the commercial application of the technology and the rapid rollout of the CO2 electroreduction for chemical manufacturing.This Account focuses on our contributions in both fundamental and applied research in the field of electrocatalytic CO2 and CO reduction reactions. We first discuss (1) the development of novel electrocatalysts for CO2/CO electroreduction to enhance the product selectivity and lower the energy consumption. Specifically, we synthesized nanoporous Ag and homogeneously mixed Cu-based bimetallic catalysts for the enhanced production of CO from CO2 and multicarbon products from CO, respectively. Then, we review our efforts in (2) the field of reactor engineering, including a dissolved CO2 H-type cell, vapor-fed CO2 three-compartment flow cell, and vapor-fed CO2 membrane electrode assembly, for enhancing reaction rates and scalability. Next, we describe (3) the investigation of reaction mechanisms using in situ and operando techniques, such as surface-enhanced vibrational spectroscopies and electrochemical mass spectroscopy. We revealed the participation of bicarbonate in CO2 electroreduction on Au using attenuated total-reflectance surface-enhanced infrared absorption spectroscopy, the presence of an "oxygenated" surface of Cu under CO electroreduction conditions using surface-enhanced Raman spectroscopy, and the origin of oxygen in acetaldehyde and other CO electroreduction products on Cu using flow electrolyzer mass spectrometry. Lastly, we examine (4) the commercial potential of the CO2 electrolysis technology, such as understanding pollutant effects in CO2 electroreduction and developing techno-economic analysis. Specifically, we discuss the effects of SO2 and NOx in CO2 electroreduction using Cu, Ag, and Sn catalysts. We also identify technical barriers that need to be overcome and offer our perspective on accelerating the commercial deployment of the CO2 electrolysis technology.

2D Conjugated Covalent Organic Frameworks: Defined Synthesis and Tailor-Made Functions.

Abstract: ConspectusCovalent organic frameworks (COFs) are an emerging class of crystalline porous polymers and have received tremendous attention and research interest. COFs can be classified into two-dimensional (2D) and three-dimensional (3D) analogues. Resembling the architectures of porous graphene, 2D conjugated COFs have exhibited promising prospects in many fields, such as gas storage and separation, heterogeneous catalysis, sensing, photocatalysis, environmental remediation, drug delivery, energy storage and conversion, and so forth. However, efficient structural design for high-throughput production of crystalline 2D COFs remains challenging.In this Account, we summarize our recent contributions to the design, synthesis, and application exploration of 2D conjugated COFs. First, we raised an efficient "two-in-one" strategy for the facile synthesis of 2D imine COFs with good reproducibility and solvent adaptability. Thanks to this elaborate molecular design strategy, we could easily modulate the topology of COFs and fabricate COF films. In addition, we developed two approaches to stabilize the 2D conjugated COFs by using planar building blocks and donor-acceptor structures. We also proposed a skeleton engineering strategy to design COFs as electrode materials, through which redox-active orthoquinone moieties were stepwise-incorporated in the skeletons of isostructural 2D imine-linked COFs. This strategy enabled systematic investigations on a series of 2D conjugated COFs with analogous structures but different numbers of active sites for energy storage, which provides a good platform to unveil the underlying structure-property relationships. In addition, we recently developed a new kind of arylamine-linked 2D conjugated COFs. The electroactive diphenylamine linkages endowed these 2D conjugated COFs with extended conjugation and improved stability, which also conferred these COFs with excellent pseudocapacitive energy storage performance. Moreover, tailor-made sulfur-rich COFs were introduced that were synthesized by selective introduction of polysulfide or sulfonyl groups on the COF skeletons and were used for Li storage and proton conduction. At the end, the key challenges of 2D conjugated COFs toward practical applications and their future prospects are suggested. We hope that this Account will evoke new inspirations and innovative work in the field of 2D conjugated COFs in the near future, especially in some burgeoning and interdisciplinary research areas.

Programmable Morphing Hydrogels for Soft Actuators and Robots: From Structure Designs to Active Functions.

Abstract: ConspectusNature provides abundant inspiration and elegant paradigms for the development of smart materials that can actuate, morph, and move on demand. One remarkable capacity of living organisms is to adapt their shapes or positions in response to stimuli. Programmed deformations or movements in plant organs are mainly driven by water absorption/dehydration of cells, while versatile motions of mollusks are based on contraction/extension of muscles. Understanding the general principles of these morphing and motion behaviors can give rise to disruptive technologies for soft robotics, flexible electronics, biomedical devices, etc. As one kind of intelligent material, hydrogels with high similarity to soft biotissues and diverse responses to external stimuli are an ideal candidate to construct soft actuators and robots.The objective of this Account is to give an overview of the fundamental principles for controllable deformations and motions of hydrogels, with a focus on the structure designs and responsive functions of the corresponding soft actuators and robots. This field has been rapidly developed in recent years with a growing understanding of working principles in natural organisms and a substantial revolution of manufacturing technologies to devise bioinspired hydrogel systems with desired structures. Diverse morphing hydrogels and soft actuators/robots have been developed on the basis of several pioneering works, ranging from bending and folding deformations of bilayer hydrogels to self-shaping of non-Euclidean hydrogel surfaces, and from thermoactuated bilayer gel "hands" to electrodriven polyelectrolyte gel "worms". These morphing hydrogels have demonstrated active functions and versatile applications in biomedical and engineering fields.In this Account, we discuss recent progress in morphing hydrogels and highlight the design principles and relevant applications. First, we introduce the fundamentals of basic deformation modes, together with generic structure features, actuation strategies, and morphing mechanisms. The advantages of in-plane gradient structures are highlighted for programmable deformations by harnessing the out-of-plane buckling with bistability nature to obtain sophisticated three-dimensional configurations. Next, we give an overview of soft actuators and robots based on morphing hydrogels and focus on the working principles of the active systems with different structure designs. We discuss the advancements of hydrogel-based soft robots capable of swift locomotion with different gaits and emphasize the significances of structure control and dynamic actuation. Then we summarize versatile applications of hydrogel-based actuators and robots in biomedicines, cargo delivery, soft electronics, information encryption, and so forth. Some hydrogel robots with a built-in feedback loop and self-sensing system exhibit collaborative functions and advanced intelligence that are informative for the design of next-generation hydrogel machines. Finally, concluding remarks are given to discuss future opportunities and remaining challenges in this field. For example, miniature hydrogel-based actuators/robots with therapeutic or diagnostic functions are highly desired for biomedical applications. The morphing mechanisms summarized in this Account should be applicable to other responsive materials. We hope that this Account will inspire more scientists to be involved in this emerging area and make contributions to reveal novel working principles, design multifunctional soft machines, and explore applications in diverse fields.

CO2 Reduction Using Water as an Electron Donor over Heterogeneous Photocatalysts Aiming at Artificial Photosynthesis

Abstract: Conspectus Photocatalytic and photoelectrochemical CO2 reduction of artificial photosynthesis is a promising chemical process to solve resource, energy, and environmental problems. An advantage of artificial photosynthesis is that solar energy is converted to chemical products using abundant water as electron and proton sources. It can be operated under ambient temperature and pressure. Especially, photocatalytic CO2 reduction employing a powdered material would be a low-cost and scalable system for practical use because of simplicity of the total system and simple mass-production of a photocatalyst material. In this Account, single particulate photocatalysts, Z-scheme photocatalysts, and photoelectrodes are introduced for artificial photosynthetic CO2 reduction. It is indispensable to use water as an electron donor (i.e., reasonable O2 evolution) but not to use a sacrificial reagent of a strong electron donor, for achievement of the artificial photosynthetic CO2 reduction accompanied by ΔG > 0. Confirmations of O2 evolution, a ratio of reacted e– to h+ estimated from obtained products, a turnover number, and a carbon source of a CO2 reduction product are discussed as the key points for evaluation of photocatalytic and photoelectrochemical CO2 reduction. Various metal oxide photocatalysts with wide band gaps have been developed for water splitting under UV light irradiation. However, these bare metal oxide photocatalysts without a cocatalyst do not show high photocatalytic CO2 reduction activity in an aqueous solution. The issue comes from lack of a reaction site for CO2 reduction and competitive reaction between water and CO2 reduction. This raises a key issue to find a cocatalyst and optimize reaction conditions defining this research field. Loading a Ag cocatalyst as a CO2 reduction site and NaHCO3 addition for a smooth supply of hydrated CO2 molecules as reactant are beneficial for efficient photocatalytic CO2 reduction. Ag/BaLa4Ti4O15 and Ag/NaTaO3:Ba reduce CO2 to CO as a main reduction reaction using water as an electron donor even in just water and an aqueous NaHCO3 solution. A Rh–Ru cocatalyst on NaTaO3:Sr gives CH4 with 10% selectivity (Faradaic efficiency) based on the number of reacted electrons in the photocatalytic CO2 reduction accompanied by O2 evolution by water oxidation. Visible-light-responsive photocatalyst systems are indispensable for efficient sunlight utilization. Z-scheme systems using CuGaS2, (CuGa)1–xZn2xS2, CuGa1–xInxS2, and SrTiO3:Rh as CO2-reducing photocatalyst, BiVO4 as O2-evolving photocatalyst, and reduced graphene oxide (RGO) and Co-complex as electron mediator or without an electron mediator are active for CO2 reduction using water as an electron donor under visible light irradiation. These metal sulfide photocatalysts have the potential to take part in Z-scheme systems for artificial photosynthetic CO2 reduction, even though their ability to extract electrons from water is insufficient. A photoelectrochemical system using a photocathode is also attractive for CO2 reduction under visible light irradiation. For example, p-type CuGaS2, (CuGa)1–xZn2xS2, Cu1–xAgxGaS2, and SrTiO3:Rh function as photocathodes for CO2 reduction under visible light irradiation. Moreover, introducing a conducting polymer as a hole transporter and surface modification with Ag and ZnS improve photoelectrochemical performance.

Large Cages of Zeolitic Imidazolate Frameworks.

Abstract: ConspectusThe design and synthesis of permanently porous materials with extended cage structures is a long-standing challenge in chemistry. In this Account, we highlight the unique role of zeolitic imidazolate frameworks (ZIFs), a class of framework materials built from tetrahedral nodes connected through imidazolate linkers, in meeting this challenge and illustrate specific features that set ZIFs apart from other porous materials. The structures of ZIFs are characteristic of a variety of large, zeolite-like cages that are covalently connected with neighboring cages and fused in three-dimensional space. In contrast to molecular cages, the fusion of cages results in extraordinary architectural and chemical stability for the passage of gases and molecules through cages and for carrying out chemical reactions within these cages while keeping the cages intact. The combination of the advantages from both cage chemistry and extended structures allows uniquely interconnected yet compartmentalized void spaces inside ZIF solids, rendering their wide range of applications in catalysis, gas storage, and gas separation.While the field of ZIFs has seen rapid development over the past decade, with hundreds of ZIF structures built from dozens of different cages of varying composition, size, and shapes reported, rational approaches to their design are largely unknown. In this Account, we summarize a vast number of cages formed in reported ZIFs and then review how the thermodynamic factors and traditional guest-templating strategies from zeolites influence the formation of cages. We highlight how the link-link interactions perform in the ZIF formation mechanism and serve as a means to target the formation of frameworks containing cages of specific sizes with structures exhibiting a level of complexity as yet unachieved in discrete coordination cages. For example, the giant ucb cage features a dimension of 46 Å and the complex moz cage is constructed from as many as 660 components.With the finding of these large and complex cages in ZIFs, we envision that the collection of cage structures will further be diversified by a mixed-linker approach utilizing a more complex combination of link-link interactions or by creating multivariant (MTV) systems that have been realized in other framework materials yet not widely employed in ZIFs. The more complicated cage structures can provide extra variations in chemical environments, and in addition to that, MTV systems can generate inhomogeneity inside each type of cage structure. The fused cages at such complexity that are difficult to be realized in solution environments will potentially enable more complex materials for smart applications.

Aromatic π-Components for Enantioselective Heck Reactions and Heck/Anion-Capture Domino Sequences.

Abstract: ConspectusOlefin functionalization represents one of the most important synthetic transformations in organic synthesis. Over the past decades, palladium-catalyzed enantioselective Heck reactions, and Heck/anion-capture domino sequences through olefin carbopalladation followed by termination of the resulting alkyl-Pd species have been extensively developed. Extension of the coupling partners from classical olefins to other π-components would enable further advances and open new space in this field. Aromatics are important and easily available bulk chemicals. Dearomative transformation of endocyclic aromatic π-bonds via the Heck reaction pathway provides an efficient and straightforward route to structurally diverse alicyclic compounds. Nevertheless, major challenges for this transformation include aromaticity breaking and reactivity and selectivity issues.Recently, we have engaged in developing catalytic enantioselective dearomative Heck reactions and related domino reactions. A range of heteroarenes and naphthalenes have been employed as novel π-coupling partners in these reactions. Through dearomative migratory insertion of endocyclic aromatic C-C π-bonds followed by interception of the transient alkyl-Pd species, enantioselective Heck reactions, reductive Heck reactions, Heck/anion-capture difunctionalization reactions, and heteroarenyne cycloisomerization reactions have been established. Relying on β-H elimination of the alkyl-Pd intermediate, we realized enantioselective dearomative Heck reactions with a range of aromatic partners, including heterocyclic indoles, pyrroles, furans, benzofurans, and more challenging carbocyclic naphthalenes. In order to avoid the utilization of organohalide electrophiles, heteroarenyne cycloisomerization reaction was developed by merging intermolecular alkyne hydropalladation with intramolecular dearomative Heck reaction. Cycloisomerization of alkyne-tethered indoles delivered chiral indolines in excellent enantioselectivities with 100% atom economy. On the other hand, Heck/anion-capture domino sequences were established through nucleophilic trapping of the alkyl-Pd intermediate. When HCO2Na was employed as a capturing reagent, the enantioselective dearomative reductive Heck reaction of indoles was realized. By employing other nucleophiles, including alkynes, N-sulfonylhydrazones, and organoboron reagents, we developed a series of dearomative difunctionalization reactions. Two vicinal stereocenters with excellent enantio- and diastereoselectivities were constructed in the corresponding Heck/Sonogashira, Heck/vinylation, and Heck/borylation reactions. Moreover, dearomative 1,4-diarylation of naphthalenes was developed through Heck/Suzuki domino reactions, in which competitive C-H arylation and the direct Suzuki reaction were almost fully inhibited in the presence of a spiro-phosphoramidite ligand.In this Account, we provide a panoramic view of our results since 2015 on enantioselective Heck reactions and related domino sequences by extending the coupling partners from classical olefins to aromatic systems. Investigations outlined in this Account established straightforward and efficient access to a variety of structurally diverse chiral heteropolycyclic molecules starting from simple and planar aromatic compounds.

Engineering Catalyst-Electrolyte Microenvironments to Optimize the Activity and Selectivity for the Electrochemical Reduction of CO2 on Cu and Ag.

Abstract: ConspectusThe electrochemical reduction of carbon dioxide (CO2R) driven by renewably generated electricity (e.g., solar and wind) offers a promising means for reusing the CO2 released during the production of cement, steel, and aluminum as well as the production of ammonia and methanol. If CO2 could be removed from the atmosphere at acceptable costs (i.e., <$100/t of CO2), then CO2R could be used to produce carbon-containing chemicals and fuels in a fully sustainable manner. Economic considerations dictate that CO2R current densities must be in the range of 0.1 to 1 A/cm2 and selectivity toward the targeted product must be high in order to minimize separation costs. Industrially relevant operating conditions can be achieved by using gas diffusion electrodes (GDEs) to maximize the transport of species to and from the cathode and combining such electrodes with a solid-electrolyte membrane by eliminating the ohmic losses associated with liquid electrolytes. Additionally, high product selectivity can be attained by careful tuning of the microenvironment near the catalyst surface (e.g., the pH, the concentrations of CO2 and H2O, and the identities of the cations in the double layer adjacent to the catalyst surface).We begin this Account with a discussion of our experimental and theoretical work aimed at optimizing catalyst microenvironments for CO2R. We first examine the effects of catalyst morphology on the production of multicarbon (C2+) products over Cu-based catalysts and then explore the role of mass transfer combined with the kinetics of buffer reactions in the local concentration of CO2 and pH at the catalyst surface. This is followed by a discussion of the dependence of the local CO2 concentration and pH on the dynamics of CO2R and the formation of specific products over both Cu and Ag catalysts. Next, we explore the impact of electrolyte cation identity on the rate of CO2R and the distribution of products. Subsequently, we look at utilizing pulsed electrolysis to tune the local pH and CO2 concentration at the catalyst surface. The last part of the discussion demonstrates that ionomer-coated catalysts in combination with pulsed electrolysis can enable the attainment of very high (>90%) selectivity to C2+ products over Cu in an aqueous electrolyte. This part of the Account is then extended to consider the difference in the catalyst-nanoparticle microenvironment, present in the catalyst layer of a membrane electrode assembly (MEA), with respect to that of a planar electrode immersed in an aqueous electrolyte.

Electrolyte Effects on CO2 Electrochemical Reduction to CO

Abstract: Conspectus The electrochemical reduction of CO2 (CO2RR) constitutes an alternative to fossil fuel-based technologies for the production of fuels and commodity chemicals. Yet the application of CO2RR electrolyzers is hampered by low energy and Faradaic efficiencies. Concomitant electrochemical reactions, like hydrogen evolution (HER), lower the selectivity, while the conversion of CO2 into (bi)carbonate through solution acid–base reactions induces an additional concentration overpotential. During CO2RR in aqueous media, the local pH becomes more alkaline than the bulk causing an additional consumption of CO2 by the homogeneous reactions. The latter effect, in combination with the low solubility of CO2 in aqueous electrolytes (33 mM), leads to a significant depletion in CO2 concentration at the electrode surface. The nature of the electrolyte, in terms of pH and cation identity, has recently emerged as an important factor to tune both the energy and Faradaic efficiency. In this Account, we summarize the recent advances in understanding electrolyte effects on CO2RR to CO in aqueous solutions, which is the first, and crucial, step to further reduced products. To compare literature findings in a meaningful way, we focus on results reported under well-defined mass transport conditions and using online analytical techniques. The discussion covers the molecular-level understanding of the effects of the proton donor, in terms of the suppression of the CO2 gradient vs enhancement of HER at a given mass transport rate and of the cation, which is crucial in enabling both CO2RR and HER. These mechanistic insights are then translated into possible implications for industrially relevant cell geometries and current densities.

Photobiocatalysis for Abiological Transformations.

Abstract: ConspectusHarnessing biocatalysts for novel abiological transformations is a longstanding goal of synthetic chemistry. Combining the merits of biocatalysis and photocatalysis allows for selective transformations fueled by visible light and offers many advantages including new reactivity, high enantioselectivity, greener syntheses, and high yields. Photoinduced electron or energy transfer enables synthetic methodologies that complement conventional two electron processes or offer orthogonal pathways for developing new reactions. Enzymes are well suited and can be tuned by directed evolution to exert control over open-shell intermediates, thereby suppressing undesirable reactions and delivering high chemo- and stereoselectivities. Within the past decade, the combination of biocatalysis and photocatalysis was mainly focused on exploiting light-regenerated cofactors to function native enzymatic activity. However, recent developments have demonstrated that the combination can unlock new-to-nature chemistry. Particularly, the discovery and application of new strategies are well poised to expand the applications of photobiocatalysis.In the past five years, our lab has been studying the combinations of photocatalysis and biocatalysis that can be applied to create new synthetic methodologies and solve challenges in synthetic organic chemistry. Our efforts have expanded the strategies for combining external photocatalysts with enzymes through the construction of a synergistic cooperative stereoconvergent reduction system consisting of photosensitized energy transfer and ene-reductase-catalyzed alkene reduction. Additionally, our efforts have also extended the capability of cofactor-dependent photoenzymatic systems to include enantioselective bimolecular radical hydroalkylations of alkenes by irradiating electron donor-acceptor complexes comprised of enzymatic redox active cofactors and unnatural substrates.In this Account, we highlight strategies developed by our group and others for combining biocatalysis and photocatalysis with the aim of introducing non-natural reactivity to enzymes. Presently, strategies applied to achieve this goal include the repurposing of natural photoenzymes, the elucidation of new photoreactivity within cofactor-dependent enzymes, the combination of external photocatalysts with enzymes, and the construction of artificial photoenzymes. By demonstrating the successful applications of these strategies for achieving selective new-to-nature transformations, we hope to spur interest in expanding the scope of photobiocatalytic systems through the use and extension of these strategies and creation of new strategies. Additionally, we hope to elucidate the intuition in synergizing the unique capabilities of biocatalysis and photocatalysis so that photobiocatalysis can be recognized as a potential solution to difficult challenges in synthetic organic chemistry.

Carbon Shell on Active Nanocatalyst for Stable Electrocatalysis.

Abstract: ConspectusElectrocatalysis is a key process for renewable energy conversion and fuel production in future energy systems. Various nanostructures have been investigated to optimize the electrocatalytic activity and realize efficient energy use. However, the long-term stability of electrocatalysts is also crucial for the sustainable and reliable operation of energy devices. Nanocatalysts are degraded by various processes during electrocatalysis, which causes critical performance loss. Recent operando analyses have revealed the mechanisms of electrocatalyst failure, and specific structures have been identified as robust against degradation. Nevertheless, achieving both high activity and robust stability with the same nanostructure is challenging because the structure-property relationships that affect activity and stability are different. The optimization of electrocatalysis is often limited by a large trade-off between activity and stability in catalyst structures. Therefore, it is essential to introduce functional structural units into catalyst design to achieve electrochemical stability while preserving high activity.In this Account, we highlight the strategic use of carbon shells on catalyst surfaces to improve the stability during electrocatalysis. For this purpose, we cover three issues in the use of carbon-shell-encapsulated nanoparticles (CSENPs) as robust and active electrocatalysts: the origin of the improved stability, the identification of active sites, and synthetic routes. Carbon shells can shield catalyst surfaces from both (electro)chemical oxidation and physical agglomeration. By limiting the exposure of the catalyst surface to an oxidizing (electro)chemical environment, carbon shells can preserve the initial active site structure during electrocatalysis. In addition, by providing a physical barrier between nanoparticles, carbon shells can maintain the high surface area of CSENPs by reducing particle agglomeration during electrocatalysis. This barrier effect is also useful for constructing more active or durable structures by annealing without surface area loss. Compared to the clear stabilizing effect, however, the effect of the shell on active sites on the CSENP surface can be puzzling. Even when they are covered by a carbon shell that can block molecular adsorption on active sites, CSENP catalysts remain active and even exhibit unique catalytic behavior. Thus, we briefly cover recent efforts to identify major active sites on CSENPs using molecular probes. Furthermore, considering the membranelike role of the carbon shell, we suggest several remaining issues that should be resolved to obtain a fundamental understanding of CSENP design. Finally, we describe two synthetic approaches for the successful carbon shell encapsulation of nanoparticles: two-step and one-step syntheses. Both the postmortem coating of nanocatalysts (two-step) and the in situ formation via precursor ligands (one step) are shown to produce a durable carbon layer on nanocatalysts in a controlled manner. The strengths and limitations of each approach are also presented to promote the further investigation of advanced synthesis methods.The hybrid structure of CSENPs, that is, the active catalyst surface and the durable carbon shell, provides an interesting opportunity in electrocatalysis. However, our understanding of CSENPs is still highly limited, and further investigation is needed to answer fundamental questions regarding both active site identification and the mechanisms of stability improvement. Only when we start to comprehend the fundamental mechanisms underlying electrocatalysis on CSENPs will electrocatalysts be further improved for sustainable long-term device operation.

N-Triftosylhydrazones: A New Chapter for Diazo-Based Carbene Chemistry.

Abstract: ConspectusOver recent decades, N-sulfonylhydrazones have attracted significant attention in academic and industrial contexts owing to their ease of preparation, versatile reactivity, high stability, and practicality. In particular, the use of N-sulfonylhydrazones as precursors for diazo compounds has paved the way for innovative and original organic reactions that are otherwise difficult to achieve. Three key developments are noteworthy in the history of N-sulfonylhydrazone chemistry: (1) Bamford and Stevens initially disclosed the application of N-tosylhydrazones as a diazo source in 1952; (2) Aggarwal and co-workers investigated N-tosylhydrazone salts as diazo precursors for sulfur ylide-mediated asymmetric epoxidation and aziridination in 2001; and (3) Barluenga, Valdés and co-workers first reported Pd-catalyzed cross-coupling reactions with N-tosylhydrazones in 2007, thus introducing the direct use of N-tosylhydrazones in carbene transfer reactions. In the past 2 decades, the synthetic exploration of N-sulfonylhydrazones in carbene chemistry has increased remarkably. N-Tosylhydrazones are the most commonly used N-sulfonylhydrazones, but they are not easy to decompose and normally need relatively high temperatures (e.g., 90-110 °C). Temperature, as a key reaction parameter, has a significant influence on the selectivity and scope of organic reactions, especially the enantioselectivity. Aggarwal and co-workers have addressed this issue by using N-tosylhydrazone salts and achieved a limited number of asymmetric organic reactions, but the method is greatly limited because the salts must be freshly prepared or stored in the dark at -20 °C prior to use. Hence, easily decomposable N-sulfonylhydrazones, especially those capable of decomposing at low temperature, should open up new opportunities for the development of N-sulfonylhydrazone chemistry. Since 2014, our group has worked toward this goal and eventually identified N-2-(trifluoromethyl)benzenesulfonylhydrazone (i.e., N-triftosylhydrazone) as an efficient diazo surrogate that can decompose at temperatures as low as -40 °C. This allowed us to carry out a range of challenging synthetic transformations and to broaden the applications of some known reactions of great relevance.In this Account, we report our achievements in the application of N-triftosylhydrazones in carbene chemistry. On the basis of the reaction types, such applications can be categorized as (i) C(sp3)-H insertion reactions, (ii) defluorinative reactions of fluoroalkyl N-triftosylhydrazones, (iii) cycloaddition reactions with alkenes and alkynes, and (iv) asymmetric reactions. Additional applications in Doyle-Kirmse rearrangements and cross-coupling with isocyanides (ours) and benzyl chlorides (from the group of Xia) are also summarized in this Account concerning miscellaneous reactions. In terms of reaction efficiency, selectivity, and functional group tolerance, N-triftosylhydrazones are generally superior to traditional N-tosylhydrazones because of their easy decomposition. Mechanistic investigations by theoretical calculations provide insights into both the reaction mechanisms and the origin of selectivity. We hope that this Account will inspire broad interest and promote new progress in the synthetic exploration of easily decomposable N-sulfonylhydrazones.

Enantioselective Synthesis of Atropisomers via Vinylidene ortho-Quinone Methides (VQMs).

Abstract: ConspectusAtropisomers, arising from conformational restriction, are inherently chiral due to the intersecting dissymmetric planes. Since there are numerous applications of enantiopure atropisomers in catalyst design, drug discovery, and material science, the asymmetric preparation of these highly prized molecules has become a flourishing field in synthetic chemistry. A number of catalysts, synthetic procedures, and novel concepts have been developed for the manufacture of the atropisomeric molecules. However, due to the intrinsic properties of different types of atropisomers featuring biaryl, hetero-biaryl, or non-biaryl architectures, only very few methods pass the rigorous inspection and are considered generally applicable. The development of a broadly applicable synthetic strategy for various atropisomers is a challenge. In this Account, we summarize our recent studies on the enantioselective synthesis of atropisomers using the vinylidene ortho-quinone methides (VQMs) as pluripotent intermediates.The most appealing features of VQMs are the disturbed aromaticity and axial chirality of the allene fragment. At the outset, the applications of VQMs in organic synthesis have been neglected due to their principal liabilities: ephemeral nature, extraordinary reactivity, and multireaction sites. The domestication of this transient intermediate was demonstrated by in situ catalytic asymmetric generation of VQMs, and the reactivity and selectivity were fully explored by judiciously modifying precursors and tuning catalytic systems. A variety of axially chiral heterocycles were achieved through five-, six-, seven- and nine-membered ring formation of VQM intermediates with different kinds of branched nucleophilic functional groups. The axially chiral C-N axis could be constructed from VQM intermediates via N-annulation or desymmetrization of preformed C-N scaffolds. We take advantage of the high electrophilicity of VQMs toward a series of sulfur and carbon based nucleophiles leading to atropisomeric vinyl arenes. Furthermore, chiral helical compounds were realized by cycloaddition or consecutive annulation of VQM intermediates. These achievements demonstrated that the VQMs could work as a nuclear parent for the collective synthesis of distinct and complex optically active atropisomers. Recently, we have realized the isolation and structural characterization of the elusive VQMs, which were questioned as putative intermediates for decades. The successful isolation of VQMs provided direct evidence for their existence and an unprecedented opportunity to directly investigate their reactivity. The good thermal stability and reserved reactivity of the isolated VQMs demonstrated their great potential as synthetic reagents and expanded the border of VQM chemistry.

Charge Transport in Organic Semiconductors: The Perspective from Nonadiabatic Molecular Dynamics

Abstract: Conspectus Organic semiconductors (OSs) are an exciting class of materials that have enabled disruptive technologies in this century including large-area electronics, flexible displays, and inexpensive solar cells. All of these technologies rely on the motion of electrical charges within the material and the diffusivity of these charges critically determines their performance. In this respect, it is remarkable that the nature of the charge transport in these materials has puzzled the community for so many years, even for apparently simple systems such as molecular single crystals: some experiments would better fit an interpretation in terms of a localized particle picture, akin to molecular or biological electron transfer, while others are in better agreement with a wave-like interpretation, more akin to band transport in metals. Exciting recent progress in the theory and simulation of charge carrier transport in OSs has now led to a unified understanding of these disparate findings, and this Account will review one of these tools developed in our laboratory in some detail: direct charge carrier propagation by quantum-classical nonadiabatic molecular dynamics. One finds that even in defect-free crystals the charge carrier can either localize on a single molecule or substantially delocalize over a large number of molecules depending on the relative strength of electronic couplings between the molecules, reorganization, or charge trapping energy of the molecule and thermal fluctuations of electronic couplings and site energies, also known as electron–phonon couplings. Our simulations predict that in molecular OSs exhibiting some of the highest measured charge mobilities to date, the charge carrier forms “flickering” polarons, objects that are delocalized over 10–20 molecules on average and that constantly change their shape and extension under the influence of thermal disorder. The flickering polarons propagate through the OS by short (≈10 fs long) bursts of the wave function that lead to an expansion of the polaron to about twice its size, resulting in spatial displacement, carrier diffusion, charge mobility, and electrical conductivity. Arguably best termed “transient delocalization”, this mechanistic scenario is very similar to the one assumed in transient localization theory and supports its assertions. We also review recent applications of our methodology to charge transport in disordered and nanocrystalline samples, which allows us to understand the influence of defects and grain boundaries on the charge propagation. Unfortunately, the energetically favorable packing structures of typical OSs, whether molecular or polymeric, places fundamental constraints on charge mobilities/electronic conductivity compared to inorganic semiconductors, which limits their range of applications. In this Account, we review the design rules that could pave the way for new very high-mobility OS materials and we argue that 2D covalent organic frameworks are one of the most promising candidates to satisfy them. We conclude that our nonadiabatic dynamics method is a powerful approach for predicting charge carrier transport in crystalline and disordered materials. We close with a brief outlook on extensions of the method to exciton transport, dissociation, and recombination. This will bring us a step closer to an understanding of the birth, survival, and annihiliation of charges at interfaces of optoelectronic devices.

Organocatalytic Enantioselective Synthesis of Axially Chiral Molecules: Development of Strategies and Skeletons.

Abstract: ConspectusThe growing importance of axially chiral architectures in different scientific domains has unveiled shortcomings in terms of efficient synthetic access and skeletal variety. This account describes our strategies in answering these challenges within the organocatalytic context where the emergence of bifunctional catalysts such as chiral phosphoric acids (CPAs) has proven invaluable in controlling the sense of axial chirality. The wide occurrence of bi(hetero)aryl skeletons in privileged structures constitutes a strong motivation to devise more effective arylation methods. Our design revolves around modulating the intrinsic nucleophilicity of aromatic amines and alcohols. The first approach involves the design of an electron-withdrawing activating group which could associate with the catalyst for reactivity enhancement and selectivity control. The resonance of arenes offers the unique mechanistic possibility to select between activating sites. C2-Azo- and nitroso-substituted naphthalenes undergo atroposelective ortho C- or N-arylation with (hetero)aromatic nucleophiles. For monocyclic benzenes, programmable charge localization leads to regioselective activation by catalytic control alone or aided by substrate design. For instance, selective addition to nitroso nitrogen enables successive annulation initiated by the amine to yield axially chiral N-arylbenzimidazoles. In a biomimetic manner, a finely tuned catalyst could direct a para-selective nucleophilic approach in the atroposelective arylation of azobenzenes. The second strategy employs electrophilic arene precursors for arylation which occurs via rearomatization with central-to-axial chirality transfer. This enabled the arylation of (imino)quinones with indoles to access phenylindole atropisomers. By adapting this chemistry with an additional oxidation event to liberate the carbonyl functionalities, aryl-o-naphthoquinone and aryl-p-quinone atropisomers were attained. Along with the development of new arylation strategies, deriving new axially chiral structures has been another consistent theme of our research program. The atroposelective functionalization of alkynes provides broad entry to atropisomeric alkenes. The monofunctionalization of alkynes through the interception of an electrophilic vinylidene-quinone-methide (VQM) intermediate with 2-naphthols yielded the new EBINOL scaffolds. By designing an internal directing group, the atroposelective dihalogenation of alkynes was realized using abundant alkali halides despite their weak nucleophilicities and poor solubilities. The atroposelective N-alkylation of alkenes was pursued to prepare multifunctionalized alkene atropisomers that could be converted into 2-arylpyrroles with chirality transfer. The synthesis of B-aryl-1,2-azaborines containing a C-B chiral axis was accomplished where the CPA catalyst effects the desymmetrization and defines the configuration of the distal C-B bond. Inspired by the axially chiral scaffold of allenes, we leveraged the developed arene activation strategy to achieve para-addition and dearomatization of judiciously designed azobenzenes, which led to structurally novel cyclohexadienylidene-based hydrazones. To complement these structures, axially chiral cyclohexadienyl oxime ethers were also attained through CPA-catalyzed condensation between hydroxylamines and spiro[4.5]trienones.

Reductive Cross-Coupling of Unreactive Electrophiles.

Abstract: ConspectusTransition-metal-catalyzed reductive coupling of electrophiles has emerged as a powerful tool for the construction of molecules. While major achievements have been made in the field of cross-couplings between organic halides and pseudohalides, an increasing number of reports demonstrates reactions involving more readily available, low-cost, and stable, but unreactive electrophiles. This account summarizes the recent results in our laboratory focusing on this topic. These findings typically include deoxygenative C-C coupling of alcohols, reductive alkylation of alkenyl acetates, reductive C-Si coupling of chlorosilanes, and reductive C-Ge coupling of chlorogermanes.The reductive deoxygenative coupling of alcohols with electrophiles is synthetically appealing, but the potential of this chemistry remains to be disclosed. Our initial study focused on the reaction of allylic alcohols and aryl bromides by the combination of nickel and Lewis acid catalysis. This method offers a selectivity that is opposite to that of the classic Tsuji-Trost reactions. Further investigation on the reaction of benzylic alcohols led to the foundation of a dynamic kinetic cross-coupling strategy with applications in the nickel-catalyzed reductive arylation of benzylic alcohols and cobalt-catalyzed enantiospecific reductive alkenylation of allylic alcohols. The titanium catalysis was later established to produce carbon radicals directly from unactivated tertiary alcohols via C-OH cleavage. The development of their coupling reactions with carbon fragments delivers new methods for the construction of all-carbon quaternary centers. These reactions have shown high selectivity for the functionalization of tertiary alcohols, leaving primary and secondary alcohols intact. Alkenyl acetates are inexpensive, stable, and environmentally friendly and are considered the most attractive alkenyl reagents. The development of reductive alkylation of alkenyl acetates with benzyl ammoniums and alkyl bromides offers mild approaches for the conversion of ketones into aliphatic alkenes.Extensive studies in this field have enabled us to extend the cross-electrophile coupling from carbon to silicon and germanium chemistry. These reactions harness the ready availability of chlorosilanes and chlorogermanes but suffer from the challenge of their low reactivity toward transition metals. Under reductive nickel catalysis, a broad range of alkenyl and aryl electrophiles couple well with vinyl- and hydrochlorosilanes. The use of alkyl halides as coupling partners led to the formation of functionalized alkylsilanes. The C-Ge coupling seems less substrate-dependent, and various common chlorogermanes couple well with aryl, alkenyl, and alkyl electrophiles. In general, functionalities such as Grignard-sensitive groups (e.g., acid, amide, alcohol, ketone, and ester), acid-sensitive groups (e.g., ketal and THP protection), alkyl fluoride and chloride, aryl bromide, alkyl tosylate and mesylate, silyl ether, and amine are tolerated. These methods provide new access to organosilicon and organogermanium compounds, some of which are challenging to obtain otherwise.

Biphen[<i>n</i>]arenes: Modular Synthesis, Customizable Cavity Sizes, and Diverse Skeletons

Abstract: Macrocyclic compounds are fundamental tools in supramolecular chemistry and have been widely used in molecular recognition, biomedicine, and materials science. The construction of new macrocycles with distinctive structures and properties would unleash new opportunities for supramolecular chemistry. Traditionally popular macrocycles, e.g., cyclodextrins, calixarenes, cucurbiturils, and pillararenes, possess specific cavities that are usually less than 10 Å in diameter; they are normally suitable for accommodating small- or medium-sized guests but cannot engulf giant molecules or structures. Furthermore, the skeletons of traditional macrocycles are impoverished and incapable of being changed; functional substituents can be introduced only on their portals.Thus, it is very challenging to construct macrocycles with customizable cavity sizes and/or diverse backbones. We have developed a versatile and modular strategy for synthesizing macrocycles, namely, biphen[n]arenes (n = 3-8), based on the structure- or function-oriented replacement of reaction modules, functional modules, and linking modules. First, two reaction modules and one functional module are connected by Suzuki-Miyaura coupling to obtain a monomer having two reaction sites. Then Friedel-Crafts alkylation between the monomer and an aldehyde (linking module) serves to afford diversely functionalized macrocycles. Moreover, large macrocycles can be achieved by using long and rigid oligo(para-phenylene) monomers. Because of the modular synthesis and plentiful molecular supplies, the biphen[n]arenes showed interesting recognition properties for both small molecules and large polypeptides. Customizable functional backbones and binding sites endowed this new family of macrocycles with peculiar self-assembly properties and potential applications in gas chromatography, pollutant capture, and physisorptive separation. Biphen[n]arenes would be a promising family of workhorses in supramolecular chemistry.In this Account, we summarize our recent work on the chemistry of biphen[n]arenes. We introduce their design and modular synthesis, including systematic exploration for reaction modules, customizable cavity sizes, skeleton functionalization, pre- and postmodification, and molecular cages. Thereafter, we discuss their host-guest properties, involving the binding for small guests by cationic/anionic/neutral biphen[n]arenes, as well as the complexation of polypeptides by large quaterphen[n]arenes. In addition, we outline the self-assembly and potential applications of this new family of macrocycles. Finally, we forecast their further development. The chemistry of biphen[n]arenes is still in its infancy. Continued exploration will not only further expand the supramolecular toolbox but also open new avenues for the use of biphen[n]arenes in the fields of biology, pharmaceutical science, and materials science.

Mimicking Color-Changing Organisms to Enable the Multicolors and Multifunctions of Smart Fluorescent Polymeric Hydrogels.

Abstract: ConspectusFluorescent polymer hydrogels (FPHs) are of significant interest for diverse emerging applications such as visualized sensing, smart display, camouflaging skins, soft actuators/robots, because they can synergize the features of classic fluorescent polymers and hydrogels. With great efforts in the past decades, the major challenge in this field has been believed to be not whether a given FPH of interest can be prepared but how to fabricate robust FPHs with multicolor tunability and multifunctional synergy. Such materials will conceptually minimize the contribution of passive materials to the mass and size of the final system, holding great potential to facilitate multiple applications. To this end, one promising way is to learn from the Nature that has superb capability to forge delicate or sometimes beyond-imagination materials. Chameleons and cephalopods serve as typical examples, which are famous for not only diverse skin color adaptability under changing environmental demands, but also synergistic skin color and body gesture changes to communicate, warn, camouflage, etc. Biological studies revealed their structural color-changing capacity derives from different types of skin chromatophores and their rational multilayer arrangement in under-skin tissues. Besides, their superb ability to heterogeneously integrate soft tissues with disparate functions into topology-optimized architectures has led to various multifunctional performances. Such natural strategies, if replicated and implemented in artificial systems, would significantly benefit and advance the development of robust FPHs for various applications.In this Account, we summarizes the key advances of smart FPHs mainly achieved by our groups. We start by introducing the unique hierarchical multilayer structures of skin chromatophores in structural color-changing reptiles, followed by an in-depth discussion on how a rational integration of bioinspiration and man-made design makes it possible to largely expand the fluorescence color-changing range of smart FPHs to almost cover the whole visible spectrum. Then, to closely mimic the multifunctional behaviors of chameleons and cephalopods, we further develop efficient strategies to introduce supramolecular interactions or heterogeneously integrating smart FPHs with other soft materials with disparate functions, producing a number of multifunctional fluorescent polymeric hydrogel systems. These robust FPHs can find many frontier applications, including bioinspired synergistic color/shape switchable hydrogel actuators/robots, smart systems with on-demand fluorescent patterning capacities for displaying or information encryption, as well as robust chemosensors for important food or environmental analytes. We expect that the discussion presented in this Account would promote better understanding of the discoloration systems in nature, and advance the development of bioinspired color-changing materials.

Emerging Electrochemical Techniques for Probing Site Behavior in Single-Atom Electrocatalysts.

Abstract: ConspectusSingle-atom catalysts (SACs) have aroused tremendous interest over the past decade, particularly in the community of energy and environment-related electrocatalysis. A rapidly growing number of recent publications have recognized it as a promising candidate with maximum atomic utilization, distinct activity, and selectivity in comparison to bulk catalysts and nanocatalysts. However, the complexity of localized coordination environments and the dispersion of isolated sites lead to significant difficulties when it comes to gaining insight into the intrinsic behavior of electrocatalytic reactions. Furthermore, the low metal loadings of most SACs make conventional ensemble measurements less likely to be accurate on the subnanoscale. Thus, it remains challenging to probe the activity and properties of individual atomic sites by available commercial instruments and analytical methods. In spite of this, continuing efforts have lately focused on the development of advanced measurement methodologies, which are very useful to the fundamental understanding of SACs. There have recently been a number of in situ/operando techniques applied to SACs, such as electron microscopy, spectroscopy, and other analysis methods, which support relevant functions to identify the active sites and reaction intermediates and to investigate the dynamic behavior of localized structures of the catalytic sites.This Account aims to present recent electrochemical probing techniques which can be used to identify single-atomic catalytic sites within solid supports. First, we describe the basic principles of molecular probe methods for the study and analysis of electrocatalytic site behavior. In particular, the in situ probing technique enabled by surface interrogation scanning electrochemical microscopy (SI-SECM) can measure the active site density and kinetic rate with high resolution. An alternative electrochemical probing technique is further demonstrated on the basis of single-entity electrochemistry, which allows the unique electrochemical imaging of the size and catalytic rate of single atoms, molecules, and clusters. The merits and limitations of different electrochemical techniques are then discussed, along with perspectives for future prospects. Apart from this, we further showcase the powerful capability of emerging electrochemical probing techniques for determining significant effects and properties of SACs for various electrocatalytic reactions, including oxygen reduction and evolution, hydrogen evolution, and nitrate reduction. Overall, electrochemical techniques with atomic resolution have greatly increased opportunities for observing, measuring, and understanding the surface and interface chemistry during energy conversion. In the future, it is anticipated that the development of electrochemical probing techniques will be advanced with innovative perspectives on the behavior and features of SACs. We hope that this Account can contribute in several ways to promoting the fundamental knowledge and technical progress of emerging electrochemical measurements for studying SACs.

Thermo-, Electro-, and Photocatalytic CO2 Conversion to Value-Added Products over Porous Metal/Covalent Organic Frameworks.

Abstract: ConspectusThe continuing increase of the concentration of atmospheric CO2 has caused many environmental issues including climate change. Catalytic conversion of CO2 using thermochemical, electrochemical, and photochemical methods is a potential technique to decrease the CO2 concentration and simultaneously obtain value-added chemicals. Due to the high energy barrier of CO2 however, this method is still far from large-scale applications which requires high activity, selectivity, and stability. Therefore, development of efficient catalysts to convert CO2 to different products is urgent. With their well-engineered pores and chemical compositions, high surface area, elevated CO2 adsorption capability, and adjustable active sites, porous crystalline frameworks including metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) are potential materials for catalytic CO2 conversion. Here, we summarize our recent work on MOFs and COFs for thermocatalytic, electrocatalytic, and photocatalytic CO2 conversion and describe the structure-activity relationships that could guide the design of effective catalysts.The first section of this paper describes imidazolium-functionalized porous MOFs, including porous liquid and cationic MOFs with nucleophilic halogen ions, which can promote thermocatalytically CO2 cycloaddition reaction with epoxides toward cyclic carbonates at one bar pressure. A porous liquid MOF takes on the role of a CO2 reservoir to tackle the low local CO2 concentrations in gas-liquid-solid heterogeneous reactions. Imidazolium-functionalized MOFs with halogen ions for CO2 cycloaddition could avoid the use of cocatalysts, and this leads to milder and more facile experimental conditions and separation processes.In a section dealing with the electrocatalytic CO2 reduction reaction (CO2RR), we developed a series of conductive porous framework materials with fast electron transmission capabilities, which afford high current densities and outperform the traditional MOF and COF catalysts that have been reported. The intrinsically conductive two-dimensional 2D MOFs and COFs nanosheets based on the fully π-conjugated phthalocyanine motif with excellent electron transport capability were prepared, and strong electron transporters were also integrated into metalloporphyrin-based COFs for CO2RR. Cu2O quantum dots and Cu nanoparticles (NPs) can be uniformly dispersed on porous conductive MOFs/COFs to afford synergistic and/or tandem electrocatalysts, which can achieve highly selective production of CH4 or C2H4 in CO2RR.A third section describes our efforts to facilitate electron-hole separation in CO2 photocatalysis. Our focus is on regulation of coordination spheres in MOFs, fabrication of the architecture of MOF heterojunctions, and engineering MOF films to facilitate photocatalytic CO2 reduction.Finally, we discuss several problems associated with the studies of MOFs and COFs for CO2 conversion and consider some prospects of the fabrication of effective porous frameworks for CO2 adsorption and conversion.

Stimuli-Responsive Crystalline Smart Materials: From Rational Design and Fabrication to Applications.

Abstract: ConspectusStimuli-responsive smart materials that can undergo reversible chemical/physical changes under external stimuli such as mechanical stress, heat, light, gas, electricity, and pH, are currently attracting increasing attention in the fields of sensors, actuators, optoelectronic devices, information storage, medical applications, and so forth. The current smart materials mostly concentrate on polymers, carbon materials, crystalline liquids, and hydrogels, which have no or low structural order (i.e., the responsive groups/moieties are disorderly in the structures), inevitably introducing deficiencies such as a relatively low response speeds, energy transformation inefficiencies, and unclear structure-property relationships. Consequently, crystalline materials with well-defined and regular molecular arrays can offer a new opportunity to create novel smart materials with improved stimuli-responsive performance. Crystalline materials include framework materials (e.g., metal-organic frameworks, MOFs; covalent organic frameworks, COFs) and molecular crystals (e.g., organic molecules and molecular cages), which have obvious advantages as smart materials compared to amorphous materials. For example, responsive groups/moieties can be uniformly installed in the skeleton of the crystal materials to form ordered molecular arrays, making energy transfer between external-stimulus signals and responsive sites much faster and more efficiently. Besides that, the well-defined structures facilitate in situ characterization of their structural transformation at the molecular level by means of various techniques and high-tech equipment such as in situ spectra and single-crystal/powder X-ray diffraction, thus benefiting the investigation and understanding of the mechanism behind the stimuli-responsive behaviors and structure-property relationships. Nevertheless, some unsolved challenges remain for crystalline smart materials (CSMs), hampering the fabrication of smart material systems for practical applications. For instance, as the materials' crystallinity increases, their processability and mechanical properties usually decrease, unavoidably hindering their practical application. Moreover, crystalline smart materials mostly exist as micro/nanosized powders, which are difficult to make stimuli-responsive on the macroscale. Thus, developing strategies that can balance the materials' crystallinity and processability and establishing macroscale smart material systems are of great significance for practical applications.In this Account, we mainly summarize the recent research progress achieved by our groups, including (i) the rational design and fabrication of new stimuli-responsive crystalline smart materials, including molecular crystals and framework materials, and an in-depth investigation of their response mechanism and structure-property relationship and (ii) creating chemical/physical modification strategies to improve the processability and mechanical properties for crystalline materials and establishing macroscale smart systems for practical applications. Overall, this Account summarizes the state-of-the-art progress of stimuli-responsive crystalline smart materials and points out the existing challenges and future development directions in the field.

Electronic Structure-Based Descriptors for Oxide Properties and Functions.

Abstract: ConspectusThe transition from fossil fuels to renewable energy requires the development of efficient and cost-effective energy storage technologies. A promising way forward is to harness the energy of intermittent renewable sources, such as solar and wind, to perform (electro)catalytic reactions to generate fuels, thus storing energy in the form of chemical bonds. However, current catalysts rely on the use of expensive, rare, or geographically localized elements, such as platinum. Widespread adoption of new (electro)catalytic technologies hinges on the discovery and development of materials containing earth-abundant elements, which can efficiently catalyze an array of (electro)chemical reactions.In the context of catalysis, descriptors provide correlations between fundamental physical properties, such as the electronic structure, and the resulting catalytic activity. The use of easily accessible descriptors has proven to be a powerful method to advance and accelerate discovery and design of new catalyst materials. The position of the oxygen electronic 2p band center has been proposed to capture the basic physical properties of oxides, including oxygen vacancy formation energy, diffusion barrier of oxygen ions, and work function. Moreover, the adsorption strength of relevant reaction intermediates at the surface of oxides can be strongly correlated with the energy of the oxygen 2p states, which affects the catalytic activity of reactions, such as oxygen electrocatalysis, and oxidative dehydrogenation of organic molecules. Such descriptors for catalytic activity can be used to predict the activity of new catalysts and understand trends and behavior among different catalysts.In this Account, we discuss how the energy of the oxygen 2p states can be used as a descriptor for oxide bulk and surface chemical properties. We show how the oxide redox properties vary linearly with the position of the oxygen 2p band center with respect to the Fermi level, and we discuss how this descriptor can be expanded across different materials and structural families, including possible generalizations to compounds outside oxides. We highlight the power of the oxygen 2p band center to predict the catalytic activity of oxides. We conclude with an outlook examining under which conditions this descriptor can be applied to predict oxide properties and possible opportunities for further refining and accelerating property predictions of oxides by leveraging material databases and machine learning.

Molecular Insight into Efficient Charge Generation in Low-Driving-Force Nonfullerene Organic Solar Cells.

Abstract: ConspectusFor organic solar cells (OSCs), charge generation at the donor/acceptor interfaces is regarded as a two-step process: driven by the interfacial energy offsets, the excitons produced by light absorption are first dissociated into the charge-transfer (CT) states, and then the CT states are further separated into free charge carriers of holes and electrons by overcoming their Coulomb attraction. Meanwhile, the CT states can recombine through radiative and nonradiative decay. Owing to the emergence of narrow-band-gap A-D-A small-molecule acceptors, nonfullerene (NF) OSCs have developed rapidly in recent years and the power conversion efficiencies (PCEs) surpass 18% now. The great achievement can be attributed to the high-yield charge generation under low exciton dissociation (ED) driving forces, which ensures both high photocurrent and small voltage loss. However, it is traditionally believed that a considerable driving force (e.g., at least 0.3 eV in fullerene-based OSCs) is essential to provide excess energy for the CT states to achieve efficient charge separation (CS). Therefore, a fundamental question open to the community is how the excitons split into free charge carriers so efficiently under low driving forces in the state-of-the-art NF OSCs.In this Account, we summarize our recent theoretical advances on the charge generation mechanisms in the low-driving-force NF OSCs. First, the A-D-A acceptors are found to dock with the D-A copolymer or A-D-A small-molecule donors mainly via local π-π interaction between their electron-withdrawing units, and such interfacial geometries can provide sufficient electronic couplings, thus ensuring fast ED. Second, the polarization energies of holes and electrons are enhanced during CS, which is beneficial to reduce the CS energy barrier and even leads to barrierless CS in the OSCs based on fluorinated A-D-A acceptors. Moreover, the exciton binding energies (Eb) are substantially decreased by the strong polarization of charge carriers for the A-D-A acceptors; especially for the Y6 system with three-dimensional molecular packing structures, the remarkable small Eb can enable direct photogeneration of free charge carriers. Accordingly, the excess energy becomes unnecessary for CS in the state-of-the-art NF OSCs. Third, to simultaneously decrease the driving force and suppress charge recombination via the triplet channel, it is imperative to reduce the singlet-triplet energy difference (ΔEST) of the narrow-band-gap A-D-A acceptors. Importantly, the intermolecular end-group π-π stacking is demonstrated to effectively decrease the ΔEST while keeping strong light absorption. Finally, hybridization of the CT states with local excitation can be induced by small interfacial energy offset. Such hybridization will result in direct population of thermalized CT states upon light absorption and a significant increase of luminescence quantum efficiency, which is beneficial to concurrently promote CS and reduce nonradiative voltage loss. We hope this Account contributes to the molecular understanding of the mechanisms of efficient charge generation with low driving forces and would be helpful for further improving the performance of organic photovoltaics in the future.

Fluorination Promotes the Cytosolic Delivery of Genes, Proteins, and Peptides.

Abstract: ConspectusThe cytosolic delivery of biomolecules such as genes, proteins, and peptides is of great importance for biotherapy but usually limited by multiple barriers during the process. Cell membrane with high hydrophobic character is one of the representative biological barriers for cytosolic delivery. The introduction of hydrophobic ligands such as aliphatic lipids onto materials or biomolecules could improve their membrane permeability. However, these ligands are lipophilic and tend to interact with the phospholipids in the membrane as well as serum proteins, which may hinder efficient intracellular delivery. To solve this issue, our research group proposed the use of fluorous ligands with both hydrophobicity and lipophobicity as ideal alternatives to aliphatic lipids to promote cytosolic delivery.In our first attempt, fluorous ligands were conjugated onto cationic polymers to increase their gene delivery efficacy. The fluorination dramatically increased the gene delivery performance at low polymer doses. In addition, the strategy greatly improved the serum tolerance of cationic polymers, which is critical for efficient gene delivery in vivo. Besides serum tolerance, mechanism studies revealed that fluorination increases multiple steps such as cellular uptake and endosomal escape. Fluorination also allowed the assembly of low-molecular-weight polymers and achieved highly efficient gene delivery with minimal material toxicity. The method showed robust efficiency for polymers, including linear polymers, branched polymers, dendrimers, bola amphiphilies, and dendronized polymers.Besides gene delivery, fluorinated polymers were also used for intracellular protein delivery via a coassembly strategy. For this purpose, two lead fluoropolymers were screened from a library of amphiphilic materials. The fluoropolymers are greatly superior to their nonfluorinated analogues conjugated with aliphatic lipids. The fluorous lipids are beneficial for polymer assembly and protein encapsulation, reduced protein denaturation, facilitated endocytosis, and decreased polymer toxicity compared to nonfluorinated lipids. The materials exhibited potent efficacy in therapeutic protein and peptide delivery to achieve cancer therapy and were able to fabricate a personalized nanovaccine for cancer immunotherapy. Finally, the fluorous lipids were directly conjugated to peptides via a disulfide bond for cytosolic peptide delivery. Fluorous lipids drive the assembly of cargo peptides into uniform nanoparticles with much improved proteolytic stability and promote their delivery into various types of cells. The delivery efficacy of this strategy is greatly superior to traditional techniques such as cell-penetrating peptides both in vitro and in vivo. Overall, the fluorination techniques provide efficient and promising strategies for the cytosolic delivery of biomolecules.