A theoretical study on π-stacking and ferromagnetism of the perylene diimide radical anion dimer and tetramer.

Ferromagnetism is rare in pure organic materials. Recently, the perylene diimide radical anion (PDI-) salt prepared through solvothermal reduction by hydrazine hydrate has shown room-temperature ferromagnetism in our work [Jiang et al., Adv. Mater., 2022, 34, 2108103]. Based on this, herein we conduct a theoretical study based on density functional theory (DFT) to reveal the stacked geometries between two NH4PDI monomers for low-spin (LS) and high-spin (HS) states and their magnetic exchange interactions (JAB) using Yamaguchi's approximate spin projection. It is observed that the pancake-bonded dimer of NH4PDI is the most stable pimer compared to others on both LS and HS potential energy surfaces. A transition of magnetic properties from strong antiferromagnetic (-1333.9 cm-1) to moderate ferromagnetic (67.0 cm-1) appears after increasing the interplanar distance between monomers and their relative rotation angle to access the HS state. According to energy decomposition analysis, the enhanced hydrogen bond formation and decrease of Pauli repulsion is able to counteract the decrease of attraction induced by electron correlation after accessing the HS state. Stacking patterns of exchange-coupled chain consisting of the NH4PDI tetramer are obtained for the HS state after geometry optimization of the structure constructed by two most stable HS pimers. The exchange interactions (51.8 cm-1, 381.2 cm-1 and 53.2 cm-1) between adjacent NH4PDI monomers are ferromagnetic in the HS state, which is in accordance with the experimentally observed room-temperature ferromagnetism.

Electrocleavage Synthesis of Solution-Processed, Imine-Linked, and Crystalline Covalent Organic Framework Thin Films.

Developing a general, facile, and direct strategy for synthesizing thin films of covalent organic frameworks (COFs) is a major challenge in this field. Herein, we report an unprecedented electrocleavage synthesis strategy to produce imine-linked COF films directly on electrodes from electrolyte solutions at room temperature. This strategy enables the cathodic exfoliation of the COF powders to nanosheets by electrochemical reduction and protonation, followed by nanosheets migrating to the anode and reproducing the COF structures by anodic oxidation. Our method is adaptable with most imine-linked COFs by virtue of the low redox potential of the imine bonds, whereas the COF films possess high crystallinity and hierarchical porosity. We highlight these COF films as a superb platform for promoting mass transfer by demonstrating their extraordinarily rapid iodine adsorption with record-high rate constants.

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways.

Melanoma is the deadliest form of skin cancer, and its incidence has continuously increased over the past 20 years. Therefore, the discovery of a novel targeted therapeutic strategy for melanoma is urgently needed. In our study, MTT-based cell proliferation assay, cell cycle, and apoptosis assays through flow cytometry, protein immunoblotting, protein immunoprecipitation, designing of melanoma xenograft models, and immunohistochemical/immunofluorescent assays were carried out to determine the detailed molecular mechanisms of a novel HSP90-PI3K dual inhibitor. Our compound, named DHP1808, was found to suppress A375 cell proliferation through apoptosis induction by activating the Fas/FasL signaling pathway; it also induced cell-cycle arrest and inhibited the cell migration and invasion of A375 cells by interfering with Hsp90-EGFR interactions and downstream signaling pathways. Our results indicate that DHP1808 could be a promising lead compound for the Hsp90/PI3K dual inhibitor.

Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma.

MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno[2,3-d]pyrimidine derivatives as potential MNK1 inhibitors. These synthetic compounds are tested in biochemical and cell proliferation assays, and six of them display potent inhibitory capacity against MNK1 kinase and cancer cell lines. Compound 12dj with strongest inhibitory capacity is transferred to molecular mechanism studies, and the results indicated that 12dj remarkably suppresses the phosphorylation of EIF4E, a substrate of MNK1. And the expression levels of MNK1, ERK1/2 and pERK1/2 are not affected by compound 12dj incubation in SUNE-1 and 786-O cells. In summary, our works suggested that these novel 4-aniline-thieno[2,3-d]pyrimidine based MNK1 inhibitors might be attractive lead compounds for targeted therapy of renal cell carcinoma and nasopharyngeal carcinoma.

Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma.

Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library. Our inhibitory compound named 8m inhibited Hsp90 and PI3Kα with an IC50 value of 38.6 nM and 48.4 nM, respectively; it displayed improved cellular activity which could effectively induce cell cycle arrest and apoptosis in melanoma cells and lead to the inhibition of cell proliferation, colony formation, migration and invasion. Our results demonstrated 8m to be a promising lead compound for further therapeutic potential assessment of Hsp90/PI3Kα dual inhibitors in melanoma targeted therapy.

Base-Promoted Synthesis of ß-Substituted-Tryptophans via a Simple and Convenient Three-Component Condensation of Nickel(II) Glycinate.

A three-component reaction of nickel(II) glycinate was conducted for the convenient synthesis of ß-substituted-tryptophans. The reaction worked smoothly under mild conditions and the procedure was simple and easy to handle.

Synthesis and in vitro evaluation of 4-substituted furano[3,2-c] tetrahydroquinolines as potential anti-cancer agents.

A convenient and mild method for the synthesis of substituted furano [3,2-c]tetrahydroquinoline derivatives was developed, using the multi-component Povarov reaction. Of the synthesized tetrahydroquinoline derivatives, compound 10a displayed the greatest cellular proliferation inhibitory activities with IC50 values of 2.5-16.7 µmol/l. In addition, 10a induced murine C6 glioma cell apoptosis in a dose-dependent manner by up-regulating the expression of Bax, caspase-3, and caspase-9, and by down-regulating Bcl-2. Our findings suggest that these novel compounds have potential as therapeutic agents via inducing mitochondrial apoptosis.

Three novel electrochemical electrodes for the fabrication of conducting polymer/SWCNTs layered nanostructures and their thermoelectric performance.

Single-walled carbon nanotubes (SWCNTs), PEDOT: PSS/SWCNTs, and SWCNTs/ PEDOT: PSS nanofilms were used as working electrodes to electrodeposit polyaniline (PANI) in a mixed alcohol solution of isopropyl alcohol (IPA), boron trifluoride ethyl ether (BFEE), and polyethylene glycol (PEG). The thermoelectric (TE) performances of the resulting nanofilms were systematically investigated. SWCNTs/ PEDOT: PSS/PANI nanofilms showed a relatively high electrical conductivity value of 232.0 S cm(-1). The Seebeck coefficient was enhanced and exhibited the values of 33.8, 25.6, and 23.0 µV K(-1) for the SWCNTs/PANI, PEDOT:PSS/SWCNTs/PANI, and SWCNTs/ PEDOT: PSS/PANI films, respectively. The maximum power factor achieved was 12.3 µW m(-1) K(-2). This technique offers a facile and versatile approach to a class of layered nanostructures, and it may provide a general strategy for fabricating a new generation of conducting polymer/SWCNTs materials for further practical applications.

Design, synthesis, and biological evaluation of novel discoidin domain receptor inhibitors for the treatment of lung adenocarcinoma and pulmonary fibrosis.

Discoidin domain receptors (DDR) play crucial roles in cell proliferation and differentiation. When DDRs are overexpressed, it has been associated with various diseases such as cancers, fibrotic disorders, and inflammation. This study aimed to expand on previous research by using a structure-based drug design approach to develop a series of new indole-urea derivatives as potent inhibitors of DDR1. Through biochemical analyses, it was found that these compounds effectively inhibited DDR1/2, with compound 7s demonstrating the highest activity against A549 cells (IC50 value of 1.84 µM) while maintaining selectivity for other kinases. In vivo studies showed that compound 7s exhibited stronger antitumor activity compared to dasatinib, without causing significant weight loss at a dose of 30 mg/kg. Further investigation revealed that compound 7s hindered the migration of A549 cells by targeting the ERK, Akt1, and EMT pathways. Additionally, cellular experiments demonstrated that compound 7s suppressed the activation of fibroblasts induced by TGF-ß1. In vivo experiments confirmed that compound 7s, at a dose of 30 mg/kg, effectively inhibited DDR1 activation, resulting in a reduction of lung injury and fibrosis induced by bleomycin. Overall, these findings highlight the potential of these novel DDR1 inhibitors as promising therapeutic candidates for the treatment of DDR-related diseases.

Band-like transport in solution-processed perylene diimide dianion films with high Hall mobility.

It is crucial to prepare high-mobility organic polycrystalline film through solution processing. However, the delocalized carrier transport of polycrystalline films in organic semiconductors has rarely been investigated through Hall-effect measurement. This study presents a strategy for building strong intermolecular interactions to fabricate solution-crystallized p-type perylene diimide (PDI) dianion films with a closer intermolecular π-π stacking distance of 3.25 Å. The highly delocalized carriers enable a competitive Hall mobility of 3 cm2 V-1 s-1, comparable to that of the reported high-mobility organic single crystals. The PDI dianion films exhibit a high electrical conductivity of 17 S cm-1 and typical band-like transport, as evidenced by the negative temperature linear coefficient of mobility proportional to T-3/2. This work demonstrates that, as the intermolecular π-π interactions become strong enough, they will display high mobility and conductivity, providing a new approach to developing high-mobility organic semiconductor materials.

Novel hybrid virtual screening protocol based on molecular docking and structure-based pharmacophore for discovery of methionyl-tRNA synthetase inhibitors as antibacterial agents.

Methione tRNA synthetase (MetRS) is an essential enzyme involved in protein biosynthesis in all living organisms and is a potential antibacterial target. In the current study, the structure-based pharmacophore (SBP)-guided method has been suggested to generate a comprehensive pharmacophore of MetRS based on fourteen crystal structures of MetRS-inhibitor complexes. In this investigation, a hybrid protocol of a virtual screening method, comprised of pharmacophore model-based virtual screening (PBVS), rigid and flexible docking-based virtual screenings (DBVS), is used for retrieving new MetRS inhibitors from commercially available chemical databases. This hybrid virtual screening approach was then applied to screen the Specs (202,408 compounds) database, a structurally diverse chemical database. Fifteen hit compounds were selected from the final hits and shifted to experimental studies. These results may provide important information for further research of novel MetRS inhibitors as antibacterial agents.

Recent Progress of Organic Semiconductor Materials in Spintronics.

Spintronics, a new discipline focusing on the spin-dependent transport process of electrons, has been developing rapidly. Spin valves are the most significant carriers of spintronics utilizing the spin freedom of electrons. It is expected to pierce "Moore's Law" and become the core component in processors of the next generation. Organic semiconductors advance in their adjustable band gap, weak spin-orbit coupling and hyperfine interaction, excellent film-forming property, having enormous promise for spin valves. Here, the principle of spin valves is introduced, and the history and progress in organic spin injection and transport materials are summarized. Then we analyze the influence of spinterface on device performance and introduce reliable methods of constructing organic spin valves. Finally, the challenges for spin valves are discussed, and the future is proposed. We aim to draw the attention of researchers to organic spin valves and promote further research in spintronics through this paper.

Chemical doping of unsubstituted perylene diimide to create radical anions with enhanced stability and tunable photothermal conversion efficiency.

N-doping of perylene diimides (PDIs) to create stable radical anions is significant for harvesting photothermal energy due to their intensive absorption in the near-infrared (NIR) region and non-fluorescence. In this work, a facile and straightforward method has been developed to control the doping of perylene diimide to create radical anions using organic polymer polyethyleneimine (PEI) as a dopant. It was demonstrated that PEI is an effective polymer-reducing agent for the n-doping of PDI toward the controllable generation of radical anions. In addition to the doping process, PEI could suppress the self-assembly aggregation and improve the stability of PDI radical anions. Tunable NIR photothermal conversion efficiency (maximum 47.9%) was also obtained from the radical-anion-rich PDI-PEI composites. This research provides a new strategy to tune the doping level of unsubstituted semiconductor molecules for varying yields of radical anions, suppressing aggregation, improving stability, and obtaining the highest radical anion-based performance.

Room-Temperature Ferromagnetism in Perylene Diimide Organic Semiconductor.

The development of pure organic magnets with high Curie temperatures remains a challenging task in material science. Introducing high-density free radicals to strongly interacting organic molecules may be an effective method to this end. In this study, a solvothermal approach with excess hydrazine hydrate is used to concurrently reduce and dissolve rigid-backbone perylene diimide (PDI) crystallites into the soluble dianion species with a remarkably high reduction potential. The as-prepared PDI powders comprising radical anion aggregates are fabricated by a subsequent self-assembly and spontaneous oxidation process. The results of magnetic measurements show that the PDI powders exhibit room-temperature ferromagnetism and a Curie temperature higher than 400 K, with a vast saturation magnetization that reaches ≈1.2 emu g-1 . Elemental analysis along with the diamagnetic signal of the ablated residue are used to rule out the possibility that the magnetism is due to metal contamination. The findings suggest that the long-range ferromagnetic ordering can survive at room-temperature in organic semiconductors, and offers a new optional way to create room-temperature magnetic semiconductors.

Wearable Thermoelectric Materials and Devices for Self-Powered Electronic Systems.

The emergence of artificial intelligence and the Internet of Things has led to a growing demand for wearable and maintenance-free power sources. The continual push toward lower operating voltages and power consumption in modern integrated circuits has made the development of devices powered by body heat finally feasible. In this context, thermoelectric (TE) materials have emerged as promising candidates for the effective conversion of body heat into electricity to power wearable devices without being limited by environmental conditions. Driven by rapid advances in processing technology and the performance of TE materials over the past two decades, wearable thermoelectric generators (WTEGs) have gradually become more flexible and stretchable so that they can be used on complex and dynamic surfaces. In this review, the functional materials, processing techniques, and strategies for the device design of different types of WTEGs are comprehensively covered. Wearable self-powered systems based on WTEGs are summarized, including multi-function TE modules, hybrid energy harvesting, and all-in-one energy devices. Challenges in organic TE materials, interfacial engineering, and assessments of device performance are discussed, and suggestions for future developments in the area are provided. This review will promote the rapid implementation of wearable TE materials and devices in self-powered electronic systems.

Regulating monomer assembly to enhance PEDOT capacitance performance via different oxidants.

The development of poly(3,4-ethylenedioxythiophene) (PEDOT) with high specific capacitance is the key to pursuing high-performance supercapacitors, and the electrochemical properties of PEDOT are closely related to the oxidation degree and conjugated chain length of its molecular chain. In this work, the influences of various oxidants (FeCl3, Fe(Tos)3 and MoCl5) on the molecular chain structure and capacitive properties of PEDOT via vapor phase polymerization were systematically investigated. Fe(Tos)3 can significantly improve the degree of oxidation and the length of the conjugated chain of PEDOT compared to FeCl3 and MoCl5, enhancing the conductivity and providing more active sites for Faraday reaction. Therefore, the PEDOT/P(Fe(Tos)3) electrode displays a considerable conductivity of 73 S cm-1, high areal capacitance (419 mF cm-2) and excellent electrochemical stability under the different bent state. Moreover, the conjugated structure strengthens the interaction between PEDOT chains, achieving good cycle stability. Therefore, Fe(Tos)3 is an ideal oxidant for obtaining high-performance PEDOT electrode materials.

Design, Synthesis, and Biological Evaluation of Pyrano[2,3-c]-pyrazole-Based RalA Inhibitors Against Hepatocellular Carcinoma.

The activation of Ras small GTPases, including RalA and RalB, plays an important role in carcinogenesis, tumor progress, and metastasis. In the current study, we report the discovery of a series of 6-sulfonylamide-pyrano [2,3-c]-pyrazole derivatives as novel RalA inhibitors. ELISA-based biochemical assay results indicated that compounds 4k-4r suppressed RalA/B binding capacities to their substrates. Cellular proliferation assays indicated that these RalA inhibitors potently inhibited the proliferation of HCC cell lines, including HepG2, SMMC-7721, Hep3B, and Huh-7 cells. Among the evaluated compounds, 4p displayed good inhibitory capacities on RalA (IC50 = 0.22 µM) and HepG2 cells (IC50 = 2.28 µM). Overall, our results suggested that a novel small-molecule RalA inhibitor with a 6-sulfonylamide-pyrano [2, 3-c]-pyrazole scaffold suppressed autophagy and cell proliferation in hepatocellular carcinoma, and that it has potential for HCC-targeted therapy.

Discovery of Thieno[2,3-d]pyrimidine-Based Hydroxamic Acid Derivatives as Bromodomain-Containing Protein 4/Histone Deacetylase Dual Inhibitors Induce Autophagic Cell Death in Colorectal Carcinoma Cells.

Bromodomain-containing protein 4 (BRD4) and histone deacetylases (HDAC) are both attractive epigenetic targets in cancer and other chronic diseases. Based on the integrated fragment-based drug design, synthesis, and in vitro and in vivo evaluations, a series of novel thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives are discovered as selective BRD4-HDAC dual inhibitors. Compound 17c is the most potent inhibitor for BRD4 and HDAC with IC50 values at nanomolar levels, as well as the expression level of c-Myc, and increases the acetylation of histone H3. Moreover, 17c presents inhibitory effects on the proliferation of colorectal carcinoma (CRC) cells via inducing autophagic cell death. It also has a good pharmacokinetic profile in rats and oral bioavailability of 40.5%. In the HCT-116 xenograft in vivo models, 17c displays potent inhibitory efficiency on tumor growth by inducing autophagic cell death and suppressing IL6-JAK-STAT signaling pathways. Our results suggest that the BRD4-HDAC dual inhibition might be an attractive therapeutic strategy for CRC.

Fishnet-Like, Nitrogen-Doped Carbon Films Directly Anchored on Carbon Cloths as Binder-Free Electrodes for High-Performance Supercapacitor.

The low specific capacitance and energy density of carbon electrode has extremely limited the wide application of supercapacitors. For developing a high-performance carbon electrode using a simple and effective method, a fishnet-like, N-doped porous carbon (FNPC) film is prepared by calcining the KOH-activated polyindole precoated on carbon cloths. The FNPC film is tightly anchored on carbon cloths without any binder. The FNPC film with 3.8 at% N content exhibits a fairly high specific capacitance of 416 F g-1 at 1.0 A g-1. Moreover, the assembled button-type cell with two FNPC film electrodes shows a high energy density of 16.4 Wh kg-1, a high power density of 67.4 kW kg-1, and long-term cyclic stability of 92% of the initial capacitance after 10 000 cycles at 10 A g-1. The high performances mainly came from the integration of pseudocapacitance and electrical double-layer capacitance behavior, wettability, fishnet-like nanostructure, as well as the low interfacial resistivity. This strategy provides a practical, uncomplicated, and low-cost design of binder-free flexible carbon materials electrode for high-performance supercapacitors.

Fused Heterocyclic Molecule-Functionalized N-Doped Reduced Graphene Oxide by Non-Covalent Bonds for High-Performance Supercapacitors.

Indole molecules with fused heteroaromatic structures can be adsorbed on the N-doped graphene surface through the π-π interaction. Therefore, the indole-functionalized N-doped graphene (InFGN) with mesopores is successfully fabricated by a simple hydrothermal method and subsequent vacuum freeze-drying process. The microstructure, thickness, element composition, pore structure, and electrochemical performance of InFGN are analyzed via SEM, TEM, AFM, BET, UV-vis, FT-IR, XPS, Raman, XRD, and electrochemical technologies. Since the five-membered aromatic heterocycles are electron-rich, the indole molecules fixed on the N-doped graphene surface can repair the structural defects generated by N doping. Electrochemical measurements show that the InFGN electrode highlights an excellent capacitance of 622.3 F g-1 at 2 A g-1 and a durable cycling life of 100.5% after 5000 charging/discharging cycle times. For further practical application, a symmetric device has been assembled by using InFGN electrodes, which realizes high-power and energy densities (18.8-20.6 Wh kg-1 at 800-8000 W kg-1). This study provides a shortcut for building green supercapacitors with enhanced energy storage performance.