Porous organic polymers (POPs) with high porosity and tunable functionalities have been widely studied for use in gas separation, catalysis, energy conversion and energy storage. However, the high cost of organic monomers, and the use of toxic solvents and high temperatures during synthesis pose obstacles for large-scale production. Herein, we report the synthesis of imine and aminal-linked POPs using inexpensive diamine and dialdehyde monomers in green solvents. Theoretical calculations and control experiments show that using meta-diamines is crucial for forming aminal linkages and branching porous networks from [2+2] polycondensation reactions. The method demonstrates good generality in that 6 POPs were successfully synthesized from different monomers. Additionally, we scaled up the synthesis in ethanol at room temperature, resulting in the production of POPs in sub-kilogram quantities at a relatively low cost. Proof-of-concept studies demonstrate that the POPs can be used as high-performance sorbents for CO2 separation and as porous substrates for efficient heterogeneous catalysis. This method provides an environmentally friendly and cost-effective approach for large-scale synthesis of various POPs.
Asymmetric ring-opening reactions of donor-acceptor cyclopropanes with 1,3-cyclodiones have been established for the synthesis of enantioenriched γ-hydroxybutyric acid derivatives in the presence of Cu(ii)/trisoxazoline catalyst. These reactions offered the desired products in 70% to 93% yields with 79% to 99% enantiomeric excesses.
This study presents a molecular surface modification approach to synthesizing a family of silver chalcogenolate clusters (SCCs) containing the same [Ag12S6] core and different surface-bonded organic ligands (DMAc or pyridines; DMAc = dimethylacetamide), with the aim of tuning the luminescence properties and increasing the structural stability of the SCCs. The SCCs displayed strong and tuneable luminescence emissions at 77 K (from green to orange to red) as influenced by the peripheral pyridine ligands. In addition, SCC 5 protected by pyridine molecules was stable in ambient air, humid air and even liquid water for a long time (up to 1 week), and it was more structurally stable than SCC 1 bonded with DMAc molecules under the same conditions. The high structural stability of SCC 5 can be explained by the ability of pyridine molecules to form strong coordination bonds with silver atoms. This study offers a new way of designing structurally stable metal nanoclusters with tuneable physicochemical properties.
[3 + 2] annulations of oxindole based spirocyclic donor-acceptor cyclopropanes and ynamides catalyzed by copper triflate have been developed for the synthesis of biologically important spirocyclopenteneoxindoles. These reactions tolerated a wide scope of substrates and provided the desired products in good to high yields (up to 90%) with up to >40 : 1 diastereoselectivities under mild conditions.
Porous organic frameworks (POFs) with predesigned structures and tunable porosities have been widely studied in adsorption and heterogeneous catalysis. Introducing ionic structure into the framework endows POFs with new functionalities that may extend their applications. Here, we report new applications for a guanidinium-based ionic POF (IPOF-Cl) in palladium scavenging and heterogeneous catalysis. Due to the ionic framework and the porous structure, the IPOF-Cl displays fast adsorption kinetics and high adsorption capacities (up to 754 mg g-1) of Na2PdCl4 in aqueous solutions via a chemisorption (ion exchange) process. Significantly, it shows excellent scavenging activity towards trace amount of [PdCl4]2- in aqueous solution. More importantly, the loaded [PdCl4]2- species on the IPOF substrate are further reduced into ultrafine Pd nanoparticles with size of â¼2-5 nm. The obtained IPOF-Pd(0) nanocomposite containing uniformly distributed Pd nanoparticles and hierarchical porous structure demonstrates high activity in catalyzing a range of Suzuki coupling reactions. This study provides new routes for the development of ionic porous organic materials for applications in metal scavenging and catalysis.
1,6-Dicarbonyl compounds, representing the formal addition products of the α-position of acetophenone derivatives to donor-acceptor cyclopropanes, were synthesized in two steps via first ring opening of donor-acceptor cyclopropanes with acyclic 1,3-diketones followed by DBU catalyzed retro-Claisen-type C-C bond cleavage reactions. In the first step, acyclic 1,3-diketones selectively worked as C-nucleophiles to add to donor-acceptor cyclopropanes. In the second step, the alkyl ketone part of the ring-opening products resulting from unsymmetrical 1,3-diketones was selectively cleaved in the presence of DBU in methanol.
Great progress has been made in the field of tumor immunotherapy in the past decade. However, the therapeutic effects of immune checkpoint blockade (ICB) against ovarian cancer are still limited. Recently, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6i) has been reported to enhance antitumor immunity in preclinical models. The combined use of CDK4/6i and ICB may be beneficial, but the effects of CDK4/6is on the tumor immune microenvironment and whether they can synergize with ICB in treating ovarian cancer remain unknown. Methods: In this study, we first assessed the antitumor efficacy of abemaciclib, an FDA-approved CDK4/6i, in a syngeneic murine ovarian cancer model. Then, immunohistochemistry, immunofluorescence and flow cytometry were performed to evaluate the number, proportion, and activity of tumor-infiltrating lymphocytes. Cytokine and chemokine production was detected both in vivo and in vitro by PCR array analysis and cytokine antibody arrays. The treatment efficacy of combined abemaciclib and anti-PD-1 therapy was evaluated in vivo, and CD8+ and CD4+ T cell activities were analyzed using flow cytometry. Lastly, the requirement for both CD8+ T cells and B cells in combination treatment was evaluated in vivo, and potential cellular mechanisms were further analyzed by flow cytometry. Results: We observed that abemaciclib monotherapy could enhance immune infiltration, especially CD8+ T cell and B cell infiltration, in the ID8 murine ovarian cancer model. Immunophenotyping analysis showed that abemaciclib induced a proinflammatory immune response in the tumor microenvironment. PCR array analysis suggested the presence of a Th1-polarized cytokine profile in abemaciclib-treated ID8 tumors. In vitro studies showed that abemaciclib-treated ID8 cells secreted more CXCL10 and CXCL13, thus recruiting more lymphocytes than control groups. Combination treatment achieved better tumor control than monotherapy, and the activities of CD8+ and CD4+ T cells were further enhanced when compared with monotherapy. The synergistic antitumor effects of combined abemaciclib and anti-PD-1 therapy depended on both CD8+ T cells and B cells. Conclusion: These findings suggest that combined treatment with CDK4/6i and anti-PD-1 antibody could improve the efficacy of anti-PD-1 therapy and hold great promise for the treatment of poorly immune-infiltrated ovarian cancer.
Aminopyridines/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , B-Lymphocytes/drug effects , Benzimidazoles/pharmacology , Immune Checkpoint Inhibitors/pharmacology , Ovarian Neoplasms/drug therapy , Aminopyridines/therapeutic use , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B-Lymphocytes/immunology , Benzimidazoles/therapeutic use , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor/transplantation , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Disease Models, Animal , Drug Synergism , Female , Humans , Immune Checkpoint Inhibitors/therapeutic use , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunology , Mice , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology
1,3-Cyclohexandione derived cyclic ketals and thiol ketals were used as O- and S-nucleophiles, respectively, for the ring opening of donor-acceptor cyclopropanes catalyzed by Cu(OTf)2 and a series of functionalized alkylene glycol diethers and dithiol diethers were obtained in good to high yields under mild conditions.
A new type of 1-unsymmetrical D-A cyclopropanes containing a cyclic enone motif was obtained by the desymmetrization of 1-symmetrical D-A cyclopropanes via first the Lewis acid-catalyzed O-nucleophilic ring-opening reaction with 1,3-cyclodiones followed by an organobase-promoted unexpected multistep intramolecular transformation.
Interlinking discrete supertetrahedral chalcogenolate clusters with conjugated bipyridine linkers form a one-dimensional coordination polymer, [Cd6Ag4(SPh)16(DMF)(H2O)(bpe)]n (1a), displaying a broader visible-light absorption and a narrower band gap than those of the discrete cluster. More importantly, the coordination polymer demonstrates enhanced activity and stability for the photocatalytic degradation of organic dye in water.
Direct asymmetric synthesis of δ-hydroxy-ß-ketoesters was accomplished via regio- and enantioselective aldol reactions of ß-ketoesters with isatins catalyzed by cinchona alkaloid thiourea derivatives. The C-C bond formation of the reactions occurred only at the γ-position of the ß-ketoesters. Reaction progress monitoring and product stability analyses under the conditions that included the catalyst indicated that the γ-position reaction products were formed kinetically. Various δ-hydroxy-ß-ketoesters bearing 3-alkyl-3-hydroxyoxindole cores relevant to the development of bioactive molecules were synthesized.
Gastric cancer (GC) is a leading cause of cancerassociated mortality worldwide. Previous studies demonstrated that long noncoding RNAs (lncRNAs) may be dysregulated in GC and may serve important roles in cancer progression. The present study aimed to investigate the role of the novel lncRNA stomach cancerassociated transcript 16 (STCAT16; Assembly Gene ID G038291) in the development and progression of GC. The present data suggested that the expression level of STCAT16 was decreased in GC tissues. The expression level of STCAT16 was identified to be associated with lymph node and tumour node metastasis stages. Furthermore, the expression level of STCAT16 was identified to be significantly associated with poor survival and prognosis. Knockdown of STCAT16 promoted proliferation, colony formation, migration and invasion of BGC823 cells. In contrast, these features were suppressed in AGS cells following overexpression of STCAT16. In vivo, tumour growth was significantly decreased following STCAT16 overexpression. Collectively, the present data suggested that the lncRNA STCAT16 may act as a tumour suppressor and may inhibit GC tumour cell growth and migration. Additionally, the decreased expression level of STCAT16 was identified to be associated with poor prognosis in patients with GC.
Cell Proliferation , RNA, Long Noncoding/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Disease Progression , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics
Chalcogenolate clusters Cd6Ag4(EPh)16(DMF)3(CH3OH) (E = S, Se) with supertetrahedral structures are isolated. Further interlinking the clusters with organic linker 4,4'-trimethylenedipiperidine in the stepwise assembly approach forms two-dimensional coordination polymers. The clusters and the coordination polymers show tunable band gaps and efficient photocatalytic activities for the degradation of aqueous dye solution. This study demonstrates the great potential of using chalcogenolate clusters and their coordination polymers in photocatalysis applications.
Densely substituted amino-functionalized benzofurans were concisely accessed via the first one-pot domino oxidation/[3+2] cyclization of a hydroquinone ester and easily accessible ynamides under mild conditions in a short time. The complex benzofurans were able to be efficiently synthesized all from simple and inexpensive starting materials in two steps.
Transforming growth factor-ß (TGF-ß) has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) during cancer progression, mainly by activating a set of pleiotropic transcription factors including SNAI2/Slug. However, the involvement of long non-coding RNAs (lncRNAs) in TGF-ß-induced Slug activation and EMT remains largely unknown. Methods: In this study, we used microarray analysis to compare lncRNA expression profiles between TGF-ß treated and untreated breast cancer cells. Then, the clinical significance of lncRNAs in breast cancer was investigated by qPCR and Kaplan-Meier survival analysis. The molecular mechanisms and EMT-promoting effects in vitro were analyzed by confocal laser microscopy, Western blotting, chromosome conformation capture (3C), chromatin isolation by RNA purification (ChIRP), ChIP, luciferase reporter assay and transwell migration assay. Lastly, the pro-metastatic effects in vivo were evaluated by bioluminescent imaging and hematoxylin and eosin (H&E) staining. Results: We observed that TGF-ß induced genome-wide changes in lncRNA levels in breast cancer cells, among which AC026904.1 and UCA1 were highly expressed in metastatic breast cancer and closely associated with poor prognosis. Mechanistic study revealed that AC026904.1 and UCA1 were upregulated by non-canonical and canonical TGF-ß pathways, respectively. Further analysis showed that AC026904.1 functions as an enhancer RNA in the nucleus, whereas UCA1 exerts a competitive endogenous RNA (ceRNA) activity in the cytoplasm. In addition, the biological functions of these two lncRNAs converged on the activation and maintenance of Slug, constituting a one-two punch in promoting EMT and tumor metastasis. Conclusion: These findings uncover for the first time that AC026904.1 and UCA1 could cooperatively upregulate Slug expression at both transcriptional and post-transcriptional levels, exerting critical roles in TGF-ß-induced EMT. The present work provides new evidence that lncRNAs function as key regulators of EMT and hold great promise to be used as novel biomarkers and therapeutic targets for metastatic breast cancer.
Breast Neoplasms/genetics , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/genetics , Snail Family Transcription Factors/metabolism , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Humans , Mice , Mice, Nude , RNA, Long Noncoding/metabolism , Transforming Growth Factor beta/metabolism , Up-Regulation
Ultrathin graphitic carbon nitride nanosheets with huge specific surface areas and exceptional photocatalytic performance of hydrogen evolution are prepared via a facile secondary calcination approach.
Chalcogenolate clusters can be interlinked with organic linkers into semiconducting coordination polymers with photocatalytic properties. Here, discrete clusters of Cd8S(SPh)14(DMF)3 were interlinked with 4,4'-bipyridine into a one dimensional coordination polymer of [Cd8S(SPh)14(DMF)(bpy)]n with helical chains. A stepwise mechanism for the assembly of the coordination polymer in DMF was revealed by an ex situ dynamic light scattering study. The cluster was electrostatically neutral and showed a penta-supertetrahedral structure. During the assembly each cluster was interlinked with two 4,4'-bipyridine molecules, which replaced the two terminal DMF molecules of the clusters. In their solid-state forms, the cluster and the coordination polymer were semiconductors with wide band gaps of 3.08 and 2.80 ev. They photocatalytically degraded rhodamine B and methylene blue in aqueous solutions. The moderate conditions used for the synthesis could allow for further in situ studies of the reaction-assembly of related clusters and coordination polymers.
Ternary supertetrahedral chalcogenolate clusters were interlinked with bipyridines into a microporous semiconducting framework with properties qualitatively different from those of the original clusters. Both the framework and the clusters were effective photocatalysts, and rapidly degraded the dye rhodamine B.
In the title complex, [Mn(C20H14N2O2)Cl]·CH3OH, the central Mn(III) atom displays a distorted square-pyramidal coordination by two N and two O atoms from the tetradentate 2,2'-[1,2-phenyl-enebis(nitrilo-methanylyl-idyne)]diphenolate ligand and one chloride ligand. The Mn(III) atom is 0.525â (4)â Å out of the square basal N2O2 least-squares plane. The complex mol-ecule is hydrogen bonded to the methanol solvent mol-ecule.
