Single-crystal polymers (SCPs): from 1D to 3D architectures.

Single-crystal polymers (SCPs) with unambiguous chemical structures at atomic-level resolutions have attracted great attention. Obtaining precise structural information of these materials is critical as it enables a deeper understanding of the potential driving forces for specific packing and long-range order, secondary interactions, and kinetic and thermodynamic factors. Such information can ultimately lead to success in controlling the synthesis or engineering of their crystal structures for targeted applications, which could have far-reaching impact. Successful synthesis of SCPs with atomic level control of the structures, especially for those with 2D and 3D architectures, is rare. In this review, we summarize the recent progress in the synthesis of SCPs, including 1D, 2D, and 3D architectures. Solution synthesis, topochemical synthesis, and extreme condition synthesis are summarized and compared. Around 70 examples of SCPs with unambiguous structure information are presented, and their synthesis methods and structural analysis are discussed. This review offers critical insights into the structure-property relationships, providing guidance for the future rational design and bottom-up synthesis of a variety of highly ordered polymers with unprecedented functions and properties.

Spiroborate-Linked Ionic Covalent Adaptable Networks with Rapid Reprocessability and Closed-Loop Recyclability.

Covalent adaptable networks (CANs) represent a novel class of polymeric materials crosslinked by dynamic covalent bonds. Since their first discovery, CANs have attracted great attention due to their high mechanical strength and stability like conventional thermosets under service conditions and easy reprocessability like thermoplastics under certain external stimuli. Here, we report the first example of ionic covalent adaptable networks (ICANs), a type of crosslinked ionomers, consisting of negatively charged backbone structures. More specifically, two ICANs with different backbone compositions were prepared through spiroborate chemistry. Given the dynamic nature of the spiroborate linkages, the resulting ionomer thermosets display rapid reprocessability and closed-loop recyclability under mild conditions. The materials mechanically broken into smaller pieces can be reprocessed into coherent solids at 120 °C within only 1 min with nearly 100% recovery of the mechanical properties. Upon treating the ICANs with dilute hydrochloric acid at room temperature, the valuable monomers can be easily chemically recycled in almost quantitative yield. This work demonstrates the great potential of spiroborate bonds as a novel dynamic ionic linkage for development of new reprocessable and recyclable ionomer thermosets.

3D Covalent Organic Framework as a Metastable Intermediate in the Formation of a Double-Stranded Helical Covalent Polymer.

The design and development of intricate artificial architectures have been pursued for decades. Helical covalent polymer (HCP) was recently reported as an unexpected topology that consists of chiral 1D polymers assembled through weak hydrogen bonds from achiral building blocks. However, many questions remained about the formation, driving force, and the single-handedness observed in each crystal. In this work, we reveal a metastable, racemic, fully covalently cross-linked, 3D covalent organic framework (COF) as an intermediate in the early stage of polymerization, which slowly converts into single-handed HCP double helices through partial fragmentation and self-sorting with the aid of a series of hydrogen bonding. Our work provides an intriguing example where weak noncovalent bonds serve as the determining factor of the overall product structure and facilitate the formation of a sophisticated polymeric architecture.

Flocking Behaviors under Hierarchical Leadership of Thermodynamic Cucker-Smale Particles with Multiplicative White Noise and Perturbation.

The thermodynamic Cucker-Smale model (TCS model) describes dynamic consistency caused by different temperatures between multi-agent particles. This paper studies the flocking behaviors of the TCS model with multiplicative white noise under hierarchical leadership. First, we introduce the corresponding model of two particles. Then, by using mathematical induction and considering the properties of differential functions, it is proved that, under certain conditions, the group can achieve flocking. Finally, we verify the conclusion through numerical simulation results. Similarly, this paper studies the above model with perturbation functions.

Carbazolylene-Ethynylene Macrocycle based Conductive Covalent Organic Frameworks.

Two covalent organic frameworks consisting of carbazolylene-ethynylene shape-persistent macrocycles with azine (MC-COF-1) or imine (MC-COF-2) linkages were synthesized via imine condensation. The obtained 2D frameworks are fully conjugated which imparts semiconducting properties. In addition, the frameworks showed high porosity with aligned accessible porous channels along the z axis, serving as an ideal platform for post-synthetic incorporation of I2 into the channels to enable electrical conductivity. The resulting MC-COF-1 showed an electrical conductivity up to 7.8×10-4  S cm-1 at room temperature upon I2 doping with the activation energy as low as 0.09 eV. Furthermore, we demonstrated that the electrical properties of both MC-COFs are switchable between electron-conducting and insulating states by simply implementing doping-regenerating cycles. The knowledge gained in this study opens new possibilities for the future development of tunable conductive 2D organic materials.

Reprocessible Triketoenamine-Based Vitrimers with Closed-Loop Recyclability.

Development of thermosets that can be repeatedly recycled via both chemical route (closed-loop) and thermo-mechanical process is attractive and remains an imperative task. In this work, we reported a triketoenamine based dynamic covalent network derived from 2,4,6-triformylphloroglucinol and secondary amines. The resulting triketoenamine based network does not have intramolecular hydrogen bonds, thus reducing its π-electron delocalization, lowering the stability of the tautomer structure, and enabling its dynamic feature. By virtue of the highly reversible bond exchange, this novel dynamic covalent bond enables the easy construction of highly crosslinked and chemically reprocessable networks from commercially available monomers. The as-made polymer monoliths exhibit high mechanical properties (tensile strength of 79.4 MPa and Young's modulus of 571.4 MPa) and can undergo a monomer-network-monomer (yields up to 90 %) recycling mediated by an aqueous solution, with the new-generation polymer capable of restoring the material strength to its original state. In addition, owing to its dynamic nature, a catalyst-free and low-temperature reprogrammable covalent adaptable network (vitrimer) was achieved. The design concept reported herein can be applied to the development of other novel vitrimers with high repressibility and recyclability, and sheds light on future design of sustainable polymers with minimal environmental impact.

Dynamic Covalent Self-sorting in Molecular and Polymeric Architectures Enabled by Spiroborate Bond Exchange.

Self-sorting is commonly observed in complex reaction systems, which has been utilized to guide the formation of single major by-design molecules. However, most studies have been focused on non-covalent systems, and using self-sorting to achieve covalently bonded architectures is still relatively less explored. Herein, we first demonstrated the dynamic nature of spiroborate linkage and systematically studied the self-sorting behavior observed in the transformation between spiroborate-linked well-defined polymeric and molecular architectures, which is enabled by spiroborate bond exchange. The scrambling between a macrocycle and a 1D helical covalent polymer led to the formation of a molecular cage, whose structures are all unambiguously elucidated by single-crystal X-ray diffraction. The results indicate that the molecular cage is the thermodynamically favored product in this multi-component reaction system. This work represents the first example of a 1D polymeric architecture transforming into a shape-persistent molecular cage, driven by dynamic covalent self-sorting. This study will further guide the design of spiroborate-based materials and open the possibilities for the development of novel complex yet responsive dynamic covalent molecular or polymeric systems.

Cyanurate-Linked Covalent Organic Frameworks Enabled by Dynamic Nucleophilic Aromatic Substitution.

We report, for the first time, highly crystalline cyanurate-linked covalent organic frameworks synthesized via dynamic nucleophilic aromatic substitution. The high crystallinity is enabled by the bond exchange reaction (self-correction) between 2,4,6-triphenoxy-1,3,5-triazine and diphenols via reversible SNAr catalyzed by triazabicyclodecene. The CN-COFs contain flexible backbones that exhibit a unique AA'-stacking due to interlayer hydrogen bonding interactions. The isoreticular expansion study demonstrates the general applicability of this synthetic method. The resulting CN-COFs exhibited good stability, as well as high CO2/N2 selectivity.

Post-synthetic modification of porous organic cages.

Porous organic cages (POCs) represent an emerging class of organic materials with intrinsic porosity. They have found various applications in supramolecular chemistry, materials science, and many other related disciplines, which stem from their molecular host-guest interactions, intrinsic and inter-cage porosity in solid state as well as the diversity of functionalities. Post-synthetic modification (PSM) has emerged as a highly viable strategy for broadening the functions and applications of POCs. Intricate structures, enhanced stability, tunable porosity and guest binding selectivity and sensitivity have been realized through PSM of POCs, which cannot be directly achieved via the predesign and bottom-up assembly from small molecule building blocks. For example, an unstable imine-linked POC can be transformed into a more stable amine-linked cage, whose cavity size can be further tuned by selective binding of some amine groups, offering unusual gas adsorption selectivity for noble gases (e.g., preferred uptake of Xe over Kr). Such improvement of the chemical stability and gas separation properties through the consolidation of linkage and adjustment of porosity is challenging to achieve otherwise. In this tutorial review, we highlight the importance and impact of PSM in engineering the properties of POC molecules, their frameworks, and composites going beyond the direct predesign synthetic strategy. The primary PSM strategies for exploring new compositions, functions and applications as well as their structure-property relationship have been summarized, including cage-to-cage transformation at the molecular level, covalent or noncovalent assembly of POCs into frameworks, and formation of composites with guest species or other additives encapsulated.

Controlled Synthesis of Palladium Nanoparticles with Size-Dependent Catalytic Activities Enabled by Organic Molecular Cages.

Particle size plays a key role in the performance of metal nanoparticles (MNPs). However, the size-controlled synthesis of MNPs still represents a challenging task. In this work, we revealed a strong solvent effect on the growth of palladium nanoparticles (PdNPs), which was directed by a porous [2 + 3] organic molecular cage (OMC, Phos-cage) containing triphenylphosphine moieties. PdNPs with different average diameters of 0.8, 1.2, and 3.3 nm supported by Phos-cage were obtained by simply varying the reaction media. The catalytic performance of such ultrafine PdNPs in the reduction of p-nitrophenol and a Suzuki-Miyaura coupling reaction has been studied, which clearly shows size-dependent catalytic activity and stability. The knowledge gained in this study, controlling the size of PdNPs supported by the OMC template in different solvents, will open new possibilities for size-controlled synthesis of ultrafine MNPs with high catalytic activity and stability.

Confined growth of ordered organic frameworks at an interface.

Given their modular synthesis, unique structural features and rich functionality, structurally ordered covalent organic frameworks (COFs) and covalent monolayers have shown great potential in a broad range of applications, such as catalysis, molecular separation, energy storage, light harvesting, etc. The synthesis of COF thin films and covalent monolayers mainly utilizes dynamic covalent chemistry (DCvC), which relies on the reversible formation and breaking of rather strong covalent bonds within molecules under certain external stimuli. Such reversible reaction conditions enable a self-correction mechanism, which can selectively resolve defect sites leading to the formation of highly ordered COF films under thermodynamic control. Novel techniques to obtain single-layer covalent nanosheets have spread throughout recent literature. Emerging interfacial polymerization techniques (e.g., air-water, liquid-liquid, liquid-solid, etc.) have been employed to successfully synthesize crystalline COF thin films from a variety of starting building blocks. Although the growth of ordered frameworks at the interface represents a rapidly developing field, the reversible reactions suitable for the synthesis of thin films or monolayers are still very limited. The identification and development of new dynamic reactions and interfacial polymerization conditions would be critical for the further development of COF thin films and covalent monolayer materials. This review covers the recent design and synthesis of COF thin films and covalent monolayers as well as their property study. The fundamental working mechanisms of different surface and interfacial polymerization and the current challenges and opportunities in this rapidly growing field are presented.

(20S) Ginsenoside Rh2 Inhibits STAT3/VEGF Signaling by Targeting Annexin A2.

Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals for tumor cell growth and surrounding angiogenesis. In this process, the tumor-associated protein Annexin A2 interacts with STAT3 and promotes Tyr705 phosphorylation and STAT3 transcriptional activation. In this study, we found that (20S) ginsenoside Rh2 (G-Rh2), a natural compound inhibitor of Annexin A2, inhibited STAT3 activity in HepG2 cells. (20S) G-Rh2 interfered with the interaction between Annexin A2 and STAT3, and inhibited Tyr705 phosphorylation and subsequent transcriptional activity. The inhibitory activity of STAT3 leaded to the negative regulation of the four VEGFs, which significantly reduced the enhanced growth and migration ability of HUVECs in co-culture system. In addition, (20S)G-Rh2 failed to inhibit STAT3 activity in cells overexpressing (20S)G-Rh2 binding-deficient Annexin A2-K301A mutant, further proving Annexin A2-mediated inhibition of STAT3 by (20S)G-Rh2. These results indicate that (20S)G-Rh2 is a potent inhibitor of STAT3, predicting the potential activity of (20S)G-Rh2 in targeted therapy applications.

(20S) Ginsenoside Rh2 Exerts Its Anti-Tumor Effect by Disrupting the HSP90A-Cdc37 System in Human Liver Cancer Cells.

(20S) ginsenoside Rh2 (G-Rh2), a major bioactive metabolite of ginseng, effectively inhibits the survival and proliferation of human liver cancer cells. However, its molecular targets and working mechanism remain largely unknown. Excitingly, we screened out heat shock protein 90 alpha (HSP90A), a key regulatory protein associated with liver cancer, as a potential target of (20S) G-Rh2 by phage display analysis and mass spectrometry. The molecular docking and thermal shift analyses demonstrated that (20S) G-Rh2 directly bound to HSP90A, and this binding was confirmed to inhibit the interaction between HSP90A and its co-chaperone, cell division cycle control protein 37 (Cdc37). It is well-known that the HSP90A-Cdc37 system aids in the folding and maturation of cyclin-dependent kinases (CDKs). As expected, CDK4 and CDK6, the two G0-G1 phase promoting kinases as well as CDK2, a key G1-S phase transition promoting kinase, were significantly downregulated with (20S) G-Rh2 treatment, and these downregulations were mediated by the proteasome pathway. In the same condition, the cell cycle was arrested at the G0-G1 phase and cell growth was inhibited significantly by (20S) G-Rh2 treatment. Taken together, this study for the first time reveals that (20S) G-Rh2 exerts its anti-tumor effect by targeting HSP90A and consequently disturbing the HSP90A-Cdc37 chaperone system. HSP90A is frequently overexpressed in human hepatoma cells and the higher expression is closely correlated to the poor prognosis of liver cancer patients. Thus, (20S) G-Rh2 might become a promising alternative drug for liver cancer therapy.

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells.

Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.

Peroxiredoxin I deficiency increases keratinocyte apoptosis in a skin tumor model via the ROS-p38 MAPK pathway.

Keratinocyte hyperproliferation is an essential link in skin cancer pathogenesis. Peroxiredoxin I (Prx I) is known to regulate cancer cell proliferation, differentiation, and apoptosis, but its role in skin cancer remains unclear. This study aimed to elucidate the role and mechanism of Prx I in skin cancer pathogenesis. Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were used to create a skin tumor model of the initiation/promotion stage of cancer. The role of Prx I in H2O2-induced keratinocyte apoptosis was also investigated. After DMBA/TPA treatment, Prx I deficiency was significantly associated with less skin tumors, lower Bcl-2 expression, and higher p-p38 and cleaved caspase-3 expressions in Prx I knockout tumors than in wild-type controls. H2O2 stimulation caused more cellular apoptosis in Prx I knockdown HaCaT cells than in normal HaCaT cells. The signaling study revealed that Bcl-2, p-p38, and cleaved caspase-3 expressions were consistent with the results in the tumors. In conclusion, the deletion of Prx I triggered the DMBA/TPA-induced skin tumor formation in vivo and in vitro by regulating the reactive oxygen species (ROS)-p38 mitogen-activated protein kinase (MAPK) pathway. These findings provide a theoretical basis for treating skin cancer.

Phosphine-Based Covalent Organic Framework for the Controlled Synthesis of Broad-Scope Ultrafine Nanoparticles.

In this work, a phosphine-based covalent organic framework (Phos-COF-1) is successfully synthesized and employed as a template for the confined growth of broad-scope nanoparticles (NPs). Ascribed to the ordered distribution of phosphine coordination sites in the well-defined pores, various stable and well-dispersed ultrafine metal NPs including Pd, Pt, Au, and bimetallic PdAuNPs with narrow size distributions are successfully prepared as determined by transmission electron microscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, and powder X-ray diffraction analyses. It is also demonstrated that the as-prepared Phos-COF-1-supported ultrafine NPs exhibit excellent catalytic activities and recyclability toward the Suzuki-Miyaura coupling reaction, reduction of nitro-phenol and 1-bromo-4-nitrobenzene, and even tandem coupling and reduction of p-nitroiodobenzene. This work will open many new possibilities for preparing COF-supported ultrafine NPs with good dispersity and stability for a broad range of applications.

Desymmetrized Vertex Design toward a Molecular Cage with Unusual Topology.

A novel low-symmetry organic molecular cage with distinctive geometry was successfully synthesized from 5,5'-(propane-2,2-diyl)bis(2-hydroxyisophthalaldehyde) and 1,2-cyclohexanediamine building blocks, through the desymmetrized vertex design strategy. Single-crystal X-ray crystallographic analysis shows that the cage contains asymmetrical and nonplanar windows, exhibiting an unprecedented C2 symmetry and an efficient packing. The molecular cage structure was also characterized by FTIR, NMR, and MALDI-TOF. Quantum chemistry studies show that the cage structure contains rare intramolecular hydrogen-hydrogen (C-H⋅⋅⋅H-C) bonding interactions. The cage crystals exhibit high iodine vapor uptake (3.78 g g-1 ), which is among the highest for porous molecular materials. The knowledge gained in this study would open new possibilities for the design and synthesis of molecular cages with novel topologies targeting a broad range of applications.

A Truxenone-based Covalent Organic Framework as an All-Solid-State Lithium-Ion Battery Cathode with High Capacity.

All-solid-state lithium ion batteries (LIBs) are ideal for energy storage given their safety and long-term stability. However, there is a limited availability of viable electrode active materials. Herein, we report a truxenone-based covalent organic framework (COF-TRO) as cathode materials for all-solid-state LIBs. The high-density carbonyl groups combined with the ordered crystalline COF structure greatly facilitate lithium ion storage via reversible redox reactions. As a result, a high specific capacity of 268 mAh g-1 , almost 97.5 % of the calculated theoretical capacity was achieved. To the best of our knowledge, this is the highest capacity among all COF-based cathode materials for all-solid-state LIBs reported so far. Moreover, the excellent cycling stability (99.9 % capacity retention after 100 cycles at 0.1 C rate) shown by COF-TRO suggests such truxenone-based COFs have great potential in energy storage applications.

Crystalline Lithium Imidazolate Covalent Organic Frameworks with High Li-Ion Conductivity.

Ionic covalent organic frameworks (ICOFs) have recently emerged as promising candidates for solid-state electrolytes. Herein, we report the first example of a series of crystalline imidazolate-containing ICOFs as single-ion conducting COF solid electrolyte materials, where lithium cations freely travel through the intrinsic channels with outstanding ion conductivity (up to 7.2 × 10-3 S cm-1) and impressively low activation energy (as low as 0.10 eV). These properties are attributed to the weak Li ion-imidazolate binding interactions and well-defined porous 2D framework structures of such ICOFs. We also investigated the structure-property relationship by varying the electronic properties of substituents (electron donating/withdrawing) that covalently attached to the imidazolate groups. We found electron-withdrawing substituents significantly improve the ion-conducting ability of imidazolate-ICOF by weakening ion-pair interactions. Our study provides a convenient bottom-up approach toward a novel class of highly efficient single-ion conducting ICOFs which could be used in all solid-state electrolytic devices.

Nuclear retention of the lncRNA SNHG1 by doxorubicin attenuates hnRNPC-p53 protein interactions.

The protein p53 plays a crucial role in the regulation of cellular responses to diverse stresses. Thus, a major priority in cell biology is to define the mechanisms that regulate p53 activity in response to stresses or maintain it at basal levels under normal conditions. Moreover, further investigation is required to establish whether RNA participates in regulating p53's interaction with other proteins. Here, by conducting systematic experiments, we discovered a p53 interactor-hnRNPC-that directly binds to p53, destabilizes it, and prevents its activation under normal conditions. Upon doxorubicin treatment, the lncRNA SNHG1 is retained in the nucleus through its binding with nucleolin and it competes with p53 for hnRNPC binding, which upregulates p53 levels and promotes p53-dependent apoptosis by impairing hnRNPC regulation of p53 activity. Our results indicate that a balance between lncRNA SNHG1 and hnRNPC regulates p53 activity and p53-dependent apoptosis upon doxorubicin treatment, and further indicate that a change in lncRNA subcellular localization under specific circumstances is biologically significant.