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However, in vitro experiments indicated that Schwann cells adhere to the four fibers, independent of these two attributes. Raman spectroscopy in native state and aqueous environment demonstrated similar secondary protein structures for dragline, cocoon, and connecting silk. In contrast, the attaching silk showed a significant lower conformation of β-sheets, crucial for the stiffness of the silk. This was in line with the in vitro experiments, where the flexible attaching silk fibers adhered to each other when placed in liquid. This resulted in their inability to guide Schwann cells, leading to the generation of cell agglomerations. This direct comparison demonstrated the crucial role of β-sheets conformation for the guidance properties of natural spider silk, providing essential insights into the necessary material properties for the integration of fibrous luminal fillings in nerve guidance conduits.In this study, a polyhedral oligomeric silsesquioxane-polycaprolactone (POSS-PCL)-cored octa-arm star-shaped glyco block copolymer (BCP), poly(ε-caprolactone)-b-poly(glucopyranose) (Star-POSS-PCL-b-PGlc) was successfully synthesized via the combination of ring opening polymerization (ROP) and MADIX (macromolecular design by interchange of xanthate) polymerization technique. Herein, initially octa(3-hydroxy-3-methylbutyl dimethylsiloxy) POSS (Star-POSS) was utilized to initiate the ROP of the ε-caprolactone to get octa-arm star-shaped Star-POSS-PCL. A successive bromination followed by xanthation of the synthesized Star-POSS-PCL polymer allowed us to further polymerize 3-O-acryloyl-1,25,6-di-O-isopropylidene-α-D-glucofuranose (AIpGlc) via MADIX polymerization. selleck chemicals Formation of the star-shaped block copolymer (BCP) was characterized using 1H NMR, FT-IR and DSC analyses. The morphology and the aqueous solution behavior of the Star-POSS-PCL-b-PGlc were analyzed using FESEM, HRTEM and DLS analyses, respectively. The lectin-binding efficiency of the star-shaped BCP having different glycopolymer block length was studied using turbidimetry assay and fluorescence quenching titration (FQT) using photoluminescence spectroscopy (PL). Here, FITC labeled concanavalin A (FITC-Con A) was used as a model lectin. The cytotoxicity study of the star-shaped BCPs over the human fibroblast cells revealed the non-toxic nature of the BCPs which open up its great potential towards drug delivery vector.The surface characteristics of bioceramics are critical in modulating the cellular events in osteogenesis. However, understanding on the effect of surface properties-derived inflammation on osteogenesis is unclear. In this study, dense biphase calcium phosphate (BCP) ceramics with various surface micropatterns were fabricated to investigate the effect of surface morphologies on the behaviors and functions of macrophages, and the subsequent cascade regulation on the osteogenic differentiation of preosteoblast. We found that the change of surface roughness and wettability of single convex in micropatterns with different sizes could make dramatic differences on the adherence, distribution and morphology of macrophages. Specifically, the patterned surface with smaller single convex area was more likely to drive macrophages towards M1-like phenotype, as was determined by the upregulated gene expression and molecular secretion of M1-specific markers compared with flat surface. Moreover, the macrophages/scaffolds-derived medium showed an obvious promotion on osteogenic differentiation of MC3T3-E1 cells that suggested the surface characteristics of BCP ceramics are important in terms of scaffolds-induced inflammation, which might contribute to its osteogenesis potential.Herein, we report the bioactivity of monodispersed nanosized reduced graphene oxide (RGO) enfolded gold nanoparticles (AuNPs) engineered polycaprolactone (PCL) based electrospun composite scaffolds. The 2D patterns of PCL based nanofibers prepared by the homogenous distribution of RGO-AuNPs exhibited unique topological and biological features such as mechanical properties, porous structure, large surface area, high electrical conductivity, biodegradability, and resemble the natural extracellular matrix (ECM) that supports the adhesion, growth, proliferation, and differentiation of stem cells. The prepared composite nanofibers based scaffolds containing RGO-AuNPs accelerated neuronal cell functions and confirmed that the optimized concentration showed cytocompatibility to PC12 and S42 cells. The 0.0005 wt% loading of RGO-AuNPs on PCL has a huge impact on neurite growth which leads to an almost one-fold increase in neurite length growth. The present study provides a new strategic design of highly efficient scaffolds that have a significant direct impact on cell activity and could be a potential bioimplant for peripheral nerve repair.The rubellins are a family of stereochemically complex anthraquinoid heterodimers containing an unprecedented chemical scaffold. Although the rubellins have been known for over three decades, no total synthesis has been achieved since their discovery. Their topology is characterized by a 6-5-6 fused ring system, five neighboring stereocenters including a quaternary center all in a convoluted core, and an anthraquinone nucleus. The rubellin architecture has been shown to inhibit and reverse the aggregation of tau protein, a therapeutically relevant target for Alzheimer's disease. Herein, we describe the first stereoselective synthesis of a member of the family, (+)-rubellin C, in 16 steps. Strategic disconnections allow expedient construction of stereochemical and topological intricacy in a short sequence of borylative and transition metal-catalyzed steps.Rocaglates, rocaglamides, and related flavagline natural products exert their remarkable anticancer activity through inhibition of eukaryotic initiation factor 4A (eIF4A) but generally display suboptimal drug-like properties. In our efforts to identify potent drug-like eIF4A inhibitors, we developed synthetic strategies for diastereoselectively functionalizing the C1 position of aza-rocaglamide scaffolds (cf. 14 and 18), which proceed via retention or inversion of configuration at C1 depending on the C2 substituent (cf. 15 and 21) and ultimately enabled the discovery of novel and potent eIF4A inhibitors such as 25.A general catalytic anti-hydroarylation of electron-deficient internal alkynes compatible with both electron-poor and electron-rich aryl reagents is reported. This selectivity is achieved through a sequential syn-carbopalladation of the alkyne by an Ar-Pd species, followed by a tandem, Ir-photocatalyzed, counter-thermodynamic E → Z isomerization. The use of ortho-substituted boronic acids enables direct access to pharmaceutically relevant heterocyclic cores via a cascade process. Mechanistic insight into the involvement of Ar-Pd versus Pd-H as an active species is provided.A new protocol has been developed for the borylation of conjugated alkenyl methyl ethers using B2Pin2 via C-O bond cleavage catalyzed by Ni(II). In this cross-coupling reaction, both E/Z isomers of alkenyl ethers are converted into (E)-alkenyl boronic esters with good reactivity. This transformation exhibits high chemoselectivity in the presence of competitive C-O bonds such as aryl ether, ester, amide, and thioether groups, thus providing a new method for the construction of various alkenyl boronates.The first example of the Pd(II)-catalyzed enantioselective amination of aryl C-H bonds is reported. The key to the successful realization of this asymmetric catalytic transformation was the identification of mono-N-protected α-amino-O-methylhydroxamic acid (MPAHA) ligands, which promote reactivity under mild conditions and control enantioselectivity. The counteranions in the solvent medium, hexafluoroacetylacetate and acetate, were also found to play key roles in stereocontrol and reactivity enhancement.Based on a copper-catalyzed radical relay strategy, the first copper-catalyzed asymmetric cyanation of alkyl-substituted alkenes has been developed. The reaction, featuring mild reaction conditions and excellent functional group compatibilities, provides an easy access to a wide array of structurally diverse enantioenriched alkyl nitriles in good yields. Notably, an unstable carbon-centered radical generated by trifluoromethyl radical addition across terminal alkenes can be enantioselectively trapped by chiral L*Cu(CN)2 with the assistance of a carbonyl group.Copper-catalyzed dearomatization and difunctionalization of pyridines have been disclosed, in which bromodifluoro-N-arylacetamide was sliced into five fragments and three or four of them were transferred to pyridine partners. Through this reaction, novel N-difluoromethyl-2-imine dihydropyridine derivatives can be conveniently accessed from commercially available 4-amino substituted pyridines. This strategy demonstrates a novel fluorination method featuring high atom economy, environmental friendliness, an easily available catalyst, and simple operation.We report the transition metal-free decarboxylative cross-coupling reactions of acyl fluorides with potassium perfluorobenzoates. Compared with traditional transition metal-catalyzed cross-couplings, this protocol presents an extremely environmentally benign pathway to afford unsymmetrical diaryl ketones. To install perfluorophenyl groups, this method highlights highly selective, inexpensive, and nontoxic conditions. The reaction system tolerates various functional groups in acyl fluorides. Remarkably, all of the starting materials can be prepared from abundant carboxylic acids and the reaction proceeds without any catalysts and additives.Indazolone cores are among the most common structural components in medicinal chemistry and can be found in many biologically active molecules. In this report, a mild and efficient approach to 2-substituted indazolones via B2(OH)4-mediated reductive N-N bond formation is developed. This strategy features mild conditions, no request for a metal catalyst, and a wide scope for both aliphatic and aromatic amines. Meanwhile, this method was further successfully applied on DNA to construct indazolone cores for a DNA-encoded library. This will enable the production of a very attractive indazolone-cored library from simple amines and scaffolds, which will provide considerable diversity.Quantification of halogen-bonding abilities is described for a series of benzimidazolium-, imidazolium- and bis(imidazolium) halogen-bond donors (XBDs) using 31P NMR spectroscopy. The measured Δδ(31P) values correlate with calculated activation free energy ΔG‡ and catalytic activity for a Friedel-Crafts indole addition. This rapid method also serves as a sensitive indicator for Brønsted acid impurities.There is an urgent need to discover new antibiotics and improve the efficacy of known antibiotics against Gram-negative bacteria. "Trojan horse" conjugates are novel and promising antibiotics. Herein we report the design and synthesis of vitamin-B12-ampicillin conjugates, which exhibited more than 500 times improved activity against Escherichia coli compared with ampicillin itself. Our studies demonstrate that the vitamin-B12 uptake pathway could be employed for effective antibiotic delivery and efficacy enhancement.