Diastereoselective [4 + 1] Cycloaddition of Alkenyl Propargyl Acetates with CO Catalyzed by [RhCl(CO)₂]₂

A class of alkenyl propargyl acetates, RCH­(OAc)­CCC­(CH₃)CH₂ (<b>5</b>), are found to undergo [4 + 1] cycloaddition with CO (1 atm) in the presence of [RhCl­(CO)₂]₂ in refluxing 1,2-dichloroethane to give cyclopentenones (<b>6</b>) in good yields. It has been demonstrated that, when the R group of <b>5</b> is a phenyl group bearing <i>o</i>-electron-withdrawing substituents, up to 10:1 diastereoselectivity and 96% yield can be achieved for the [4 + 1] cycloaddition. This process provides a convenient method to construct highly functionalized cyclopentenones that are useful in organic synthesis

Spleen-Targeted mRNA Delivery by Amphiphilic Carbon Dots for Tumor Immunotherapy

In recent years, the application of mRNA vaccine-based tumor immunotherapy invigorated anti-tumor therapy. However, the low efficiency of mRNA delivery and the lack of targeting ability in vivo are the major obstacles to achieving highly efficient immunotherapy. In this work, we report a chemical library of amphiphilic carbon dots (ACDs) and the synthesized ACDs were applied to mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can smoothly bind with mRNA to form ACDs@mRNA nanocomplexes, and the fluorescent properties of the ACDs afforded the nanoparticles with bio-imaging ability. By screening of the ACDs, O12-Tta-CDs were found to have optimal mRNA transfection efficiency and the ability of spleen-targeted delivery. In addition, O12-Tta-CDs can well transfect the immune cells and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Furthermore, O12-Tta-CDs@OVA-mRNA was successfully applied to inhibit tumor growth, and more specific T-cell infiltration was observed in spleen and tumors of mice after treatment in the E.G7-OVA tumor model. Besides, O12-Tta-CDs@OVA-mRNA also achieved a good therapeutic effect in tumor recurrence inhibition and tumor prophylactic experiments. This study provided a new direction for the design of mRNA vectors, which is promising in tumor immunotherapy

Spleen-Targeted mRNA Delivery by Amphiphilic Carbon Dots for Tumor Immunotherapy

In recent years, the application of mRNA vaccine-based tumor immunotherapy invigorated anti-tumor therapy. However, the low efficiency of mRNA delivery and the lack of targeting ability in vivo are the major obstacles to achieving highly efficient immunotherapy. In this work, we report a chemical library of amphiphilic carbon dots (ACDs) and the synthesized ACDs were applied to mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can smoothly bind with mRNA to form ACDs@mRNA nanocomplexes, and the fluorescent properties of the ACDs afforded the nanoparticles with bio-imaging ability. By screening of the ACDs, O12-Tta-CDs were found to have optimal mRNA transfection efficiency and the ability of spleen-targeted delivery. In addition, O12-Tta-CDs can well transfect the immune cells and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Furthermore, O12-Tta-CDs@OVA-mRNA was successfully applied to inhibit tumor growth, and more specific T-cell infiltration was observed in spleen and tumors of mice after treatment in the E.G7-OVA tumor model. Besides, O12-Tta-CDs@OVA-mRNA also achieved a good therapeutic effect in tumor recurrence inhibition and tumor prophylactic experiments. This study provided a new direction for the design of mRNA vectors, which is promising in tumor immunotherapy

BINOL-Based Fluorescent Sensor for Recognition of Cu(II) and Sulfide Anion in Water

A multifunctional fluorescent sensor based on a cyclen-appended BINOL derivative (<b>R-1</b>) was synthesized and characterized. It can display on–off-type fluorescence change with high selectivity toward Cu­(II) among 19 metal ions in 100% aqueous solution. Furthermore, the in situ generated <b>R-1–Cu­(II)</b> ensemble could recover the quenched fluorescence upon the addition of sulfide anion resulting in a off–on-type sensing with a detection limit of micromolar range in the same medium. No interference was observed from other biothiols and anions, including GSH, l-Cys, DTT, and sulfates, making it a highly sensitive and selective sulfide probe

Spleen-Targeted mRNA Delivery by Amphiphilic Carbon Dots for Tumor Immunotherapy

In recent years, the application of mRNA vaccine-based tumor immunotherapy invigorated anti-tumor therapy. However, the low efficiency of mRNA delivery and the lack of targeting ability in vivo are the major obstacles to achieving highly efficient immunotherapy. In this work, we report a chemical library of amphiphilic carbon dots (ACDs) and the synthesized ACDs were applied to mRNA delivery, bio-imaging, and tumor immunotherapy. The ACDs can smoothly bind with mRNA to form ACDs@mRNA nanocomplexes, and the fluorescent properties of the ACDs afforded the nanoparticles with bio-imaging ability. By screening of the ACDs, O12-Tta-CDs were found to have optimal mRNA transfection efficiency and the ability of spleen-targeted delivery. In addition, O12-Tta-CDs can well transfect the immune cells and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Furthermore, O12-Tta-CDs@OVA-mRNA was successfully applied to inhibit tumor growth, and more specific T-cell infiltration was observed in spleen and tumors of mice after treatment in the E.G7-OVA tumor model. Besides, O12-Tta-CDs@OVA-mRNA also achieved a good therapeutic effect in tumor recurrence inhibition and tumor prophylactic experiments. This study provided a new direction for the design of mRNA vectors, which is promising in tumor immunotherapy

Sodium Alginate-Doping Cationic Nanoparticle As Dual Gene Delivery System for Genetically Bimodal Therapy

Photodynamic therapy occupies an important position in cancer therapy because of its minimal invasiveness and high spatiotemporal precision, and photodynamic/gene combined therapy is a promising strategy for additive therapeutic effects. However, the asynchronism and heterogeneity between traditional chemical photosensitizers and nucleic acid would restrict the feasibility of this strategy. KillerRed protein, as an endogenous photosensitizer, could be directly expressed and take effect in situ by transfecting KillerRed reporter genes into cells. Herein, a simple and easily prepared sodium alginate (SA)-doping cationic nanoparticle SA@GP/DNA was developed for dual gene delivery. The nanoparticles could be formed through electrostatic interaction among sodium alginate, polycation, and plasmid DNA. The title complex SA@GP/DNA showed good biocompatibility and gene transfection efficiency. Mechanism studies revealed that SA doping could facilitate the cellular uptake and DNA release. Furthermore, SA@GP/DNA was applied to the codelivery of p53 and KillerRed reporter genes for the synergistic effect combining p53-mediated apoptosis therapy and KillerRed-mediated photodynamic therapy. The ROS generation, tumor cell growth inhibition, and apoptosis assays proved that the dual-gene transfection could mediate the better effect compared with single therapy. This rationally designed dual gene codelivery nanoparticle provides an effective and promising platform for genetically bimodal therapy

Catalytic Asymmetric Enyne Addition to Aldehydes and Rh(I)-Catalyzed Stereoselective Domino Pauson–Khand/[4 + 2] Cycloaddition

The 1,1′-bi-2-naphthol–ZnEt₂–Ti­(OⁱPr)₄–Cy₂NH system is found to catalyze the 1,3-enyne addition to aliphatic aldehydes as well as other aldehydes at room temperature with 75–96% yield and 82–97% ee. This system is also broadly applicable for the highly enantioselective reaction of other alkyl-, aryl-, and silylalkynes with structurally diverse aldehydes. The propargylic alcohols prepared from the catalytic asymmetric enyne addition to aliphatic aldehydes are used to prepare a series of optically active trienynes. In the presence of a catalytic amount of [RhCl­(CO)₂]₂ and 1 atm of CO, the optically active trienynes undergo highly stereoselective domino Pauson–Khand/[4 + 2] cycloaddition to generate optically active multicyclic products. The Rh­(I) catalyst is also found to catalyze the coupling of a diyne with CO followed by [4 + 2] cycloaddition to generate an optically active multicyclic product. These transformations are potentially useful for the asymmetric synthesis of polyquinanes containing a quaternary chiral carbon center

Sulfonylation of Five-Membered Heterocycles via an S_NAr Reaction

An efficient, concise, and transition metal-free synthesis of functionalized sulfonylated five-membered heterocyclic compounds via an S_NAr reaction has been developed. Using commercially available sodium sulfinates as sulfonylation reagents, various five-membered heterocyclic sulfones were obtained in good yields

Small Combinatorial Library of Lipidoids as Nanovectors for Gene Delivery

A small library of 27 lipidoids was set up by a combinatorial approach. These lipidoids were prepared from three polyamines and nine reactants with alkyl tail via epoxide ring-opening reaction or Michael addition. The polyamines include tris­(2-aminoethyl)­amine (<b>TAEA</b>), 1,4,7-triazacyclononane (<b>TACN</b>), and 1,4,7,10-tetraazacyclododecane (<b>Cyclen</b>), while the structures of nine reactants vary in both reacting groups and chain lengths. The lipidoids were obtained without any solvent and used directly without further purification, and no helper lipid was needed for the interaction with DNA. Initial screening by the EGFP transfection assay selected six lipidoid nanoparticles with good transfection efficiency for further investigation. Gel electrophoresis, TEM, and relative studies reveal that these lipidoids have good DNA condensation capability and the formed DNA complexes have good stability toward serum or nuclease. Quantitative transfection study with luciferase reporter gene showed that <b>TACN-O14</b> could give 1.8 times higher efficiency than Lipofectamine 2000 in A549 cells, while <b>TAEA-A12</b> may give 4.2 times higher efficiency in 7402 cells. Moreover, serum would not inhibit their transfection, and even lightly increased efficiencies could be obtained with serum. Mechanism studies including flow cytometry and CLSM revealed that the higher transfection efficiency of the lipidoid might be attributed to the more rapid and efficient endosome/lysosome escape

Sulfonylation of Five-Membered Heterocycles via an S_NAr Reaction

An efficient, concise, and transition metal-free synthesis of functionalized sulfonylated five-membered heterocyclic compounds via an S_NAr reaction has been developed. Using commercially available sodium sulfinates as sulfonylation reagents, various five-membered heterocyclic sulfones were obtained in good yields