Longqiang Xiao

Enzymatically cross-linked hyaluronic acid/graphene oxide nanocomposite hydrogel with pH-responsive release.

Hyaluronic acid (HA) is made up of repeating disaccharide units (β-1,4-d-glucuronic acid and β-1,3-N-acetyl-d-glucosamine) and is a major constituent of the extracellular matrix. HA and its derivatives which possess excellent biocompatibility and physiochemical properties have been studied in drug delivery and tissue engineering applications. Tyramine-based HA hydrogel with good compatibility to cell and tissue has been reported recently. However, inferior mechanical property may limit the biomedical application of the HA hydrogel. In this study, HA/graphene oxide (GO) nanocomposite (NC) hydrogel was prepared through a horseradish peroxidase catalyzed in situ cross-linking process. As compared with pure HA hydrogels, incorporation of GO to the HA matrix could significantly enhance the mechanical properties (storage moduli 1800 Pa) of the hydrogel and prolong the release of rhodamine B (RB) as the model drug from the hydrogel (33 h) as well. In addition, due to the multiple interactions between GO and RB, the NC hydrogels showed excellent pH-responsive release behavior. The release of RB from the NC hydrogel was prolonged at low pH (pH 4.0) in the presence of GO, which could be attributed to the enhanced interactions between GO and HA as well as with RB. In situ three-dimensional encapsulation of mouse embryonic fibroblasts (BALB 3T3 cells) in the NC hydrogels and cytotoxicity results indicated the cytocompatibility of both the enzymatic cross-linking process and HA/GO NC hydrogels (cell viability 90.6 ± 4.25%). The enzymatically catalyzed fabrication of NC hydrogels proved to be an easy and mild approach, and had great potential in the construction of both tissue engineering scaffolds and stimuli-responsive drug release matrices.

Biopolymer-based supramolecular micelles from β-cyclodextrin and methylcellulose

Supramolecular polymer micelles (SMPMs) were constructed from natural and natural-derived polymers: β-cyclodextrin (β-CD)/maleic anhydride modified β-cyclodextrin (MAh-β-CD) and methylcellulose (MC) in aqueous solution by one-pot self-assembly procedure, in which, β-CD and MAh-β-CD inclusion complexes were used as the hydrophilic shell and the free MC as the core. The shapes of the SMPMs were regular spheres with diameters of 25±5 nm. The critical micelle concentrations, calculated from steady-state fluorescence emission spectra, were around 15.13 and 20.89 mg/L for MC/β-CD and MC/MAh-β-CD SMPMs, respectively. The in vitro drug release behaviors of the micelles were studied using prednisone acetate as a model drug, and the results showed that the MC/MAh-β-CD micelle had a drug-enrichment core and excellent drug released behaviors with a sustaining release time of 700 h.

Synthesis and characterization of fluorescent oligo(3,4,5-triethoxycarbonyl-2-pyrazoline)

Pseudopeptide oligomers as newly developing fluorescent macromolecules are of significant importance and fairly attractive in bioimaging of living cells. We report that a type of efficient fluorescent pseudopeptide oligo(3,4,5-triethoxycarbonyl-2-pyrazoline) is prepared by the novel cyclo-polycondensation of 3,4,5-triethoxycarbonyl-2-pyrazoline that is a weakly-fluorescent chromophore. The pseudopeptide oligomer exhibits a strong red-shift and remarkable fluorescence enhancement compared with the monomer 2-pyrazoline and images living cells in good quality, even though it only consists of fewer than 70 glycine residues whereas for the famous green fluorescent protein (GFP) the amount of the various natural amino acid residues is 238. Oligo(3,4,5-triethoxycarbonyl-2-pyrazoline) is a GFP-mimetic but structurally-simplified fluorescent pseudopeptide with simple chemistry, generated from the only natural resource of glycine.

Denitrogen alkene polymerization of bisdiazo compounds by copper(II) catalysts

Bisdiazo compounds were synthesized and underwent denitrogen alkene polymerization (DNAP) via the formation of an sp2 carbon bond in the presence of copper(II) catalysts, affording unsaturated polymers with molecular weights in the range of 2900 to 35 400 Da. The copper-catalyzed denitrogen alkene polymerization of bisdiazo compounds allows the efficient synthesis of unsaturated polyesters.

Kinetic study of carbene polymerization of ethyl diazoacetate by palladium and rhodium catalysts

Kinetic studies of the carbene polymerization of ethyl diazoacetate (EDA) by palladium (Pd) or rhodium (Rh) catalysts were investigated by real-time Fourier transform infrared (FTIR) spectroscopy. Both (L-prolinate)RhI(1,5-cyclooctadiene) and (L-prolinate)RhI(2,5-norbornadiene) mediated EDA polymerization were proved to be first order reactions, suggesting that the formation of “Rh-carbenoid” is the rate determining step. The activation energy (11.24 kJ mol−1) of the polymerization of “carbenes” generated from EDA with (L-prolinate)RhI(1,5-cyclooctadiene) as the catalyst was calculated from kinetic data via the Arrhenius equation. On the other hand, the polymerizations of EDA catalyzed by three kinds of Pd-catalysts were revealed as zero order reactions, suggesting that the rate determining step involves the formation of an EDA–Pd transition state complex through a coordinated step. Refilling more EDA to the (bis(acetonitrile)dichloropalladium)-mediated carbene polymerization system did not change the reaction order. The rate constant increases gradually with the increase of the dosage of the catalyst and decreases with the cycle-index, which proves the formation of “EDA–Pd transition state complex” and the propagating species with Pd–C bonds at the end of the polymer chain.

Host-guest chemistry of cyclodextrin carbamates and cellulose derivatives in aqueous solution.

Supramolecular polymer micelles were prepared on basis of the inclusion complexation between cyclodextrin carbamates and cellulose derivatives in aqueous media. Cyclodextrin carbamates were synthesized by microwave-assisted method from cyclodextrin and urea. The urea modified cyclodextrin shows the higher yield than the physical mixture of urea/cyclodextrin in the micellization with cellulose derivatives. The supramolecular structure of the core-shell micelles was demonstrated by (1)H NMR spectra, TEM images, and fluorescence spectra. The drug release behavior of the supramolecular polymer micelles was evaluated using prednisone acetate as a model drug. The drug loaded micelles showed steady and long time drug release behavior. With these properties, the supramolecular polymer micelles are attractive as drug carriers for pharmaceutical applications.

One-step synthesis of polypyrazoles and self-assembled polypyrazole–copper catalysts for click chemistry

Polypyrazoles with molecular weights in the range of 6500–9300 g mol−1 and yields in the range of 71.4–82.5% were synthesized successfully by catalyst-free 1,3-dipolar cycloaddition of bisdiazo compounds to bisalkynes under thermal conditions and lost merely 5% of their weights at temperatures higher than 298 °C. The porous polypyrazole–copper complex with pore diameters in the range of 1–2 μm was prepared by the coordination of polypyrazole and copper sulfate (CuSO4), which is a reusable catalyst for the Huisgen 1,3-diploar cycloaddition of alkynes and organic azides to give the corresponding triazoles with yields over 90%.

Metal-Diazo Radicals of α-Carbonyl Diazomethanes.

Metal-diazo radicals of α-carbonyl diazomethanes are new members of the radical family and are precursors to metal-carbene radicals. Herein, using electron paramagnetic resonance spectroscopy with spin-trapping, we detect diazo radicals of α-carbonyl diazomethanes, induced by [RhICl(cod)]2, [CoII(por)] and PdCl2, at room temperature. The unique quintet signal of the Rh-diazo radical was observed in measurements of α-carbonyl diazomethane adducts of [RhICl(cod)]2 in the presence of 5,5-dimethyl-pyrroline-1-N-oxide (DMPO). DFT calculations indicated that 97.2% of spin density is localized on the diazo moiety. Co- and Pd-diazo radicals are EPR silent but were captured by DMPO to form spin adducts of DMPO-N∙ (triplet-of-sextets signal). The spin-trapping also provides a powerful tool for detection of metal-carbene radicals, as evidenced by the DMPO-trapped carbene radicals (DMPO-C∙, sextet signal) and 2-methyl-2-nitrosopropane-carbene adducts (MNP-C∙, doublet-of-triplets signal). The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals.

Polymeric palladium-mediated carbene polymerization

A metalloenzyme-inspired polymeric palladium catalyst, which was prepared by self-assembly of a polymeric imidazole ligand with PdCl2, promoted carbene polymerization with high catalytic activity and reusability. Besides the atactic polycarbethoxycarbene (PCEC), a small amount of stereoregular PCEC was also obtained with poly(imidazole-Pd)-mediated polymerization of ethyl diazoacetate (EDA). This is the first example that a stereoregular polycarbene in an isolated form is obtained with a palladium-initiating system, suggesting that the steric polymeric imidazole ligand could affect the carbene insertion process. Detailed end group analyses on the obtained atactic and stereoregular PCEC revealed the chain initiation and chain termination mechanisms. XPS analyses on the oxidation state changes of the palladium center exhibited that PdII was reduced to PdI, which suggests that an intramolecular electron transfer process occurred during the interaction of palladium and EDA. Kinetic studies showed a zero order kinetic dependent on the concentration of EDA, which indicates a strong binding of EDA on the catalyst preceding carbene formation. With the addition of a radical inhibitor, the reaction rate was found to be greatly decreased. In the presence of a spin trap, a striking electron paramagnetic resonance (EPR) spectrum could be detected, which suggests the involvement of radical intermediates. DFT calculations on the proposed Pd-carbene radical species supported the EPR analyses, which assigned a significant amount of spin density on the carbene-carbon atom. Based on these results, we proposed an unprecedented metal-carbene radical polymerization mechanism, which occurs through a stepwise carbene radical migration and insertion process to afford polycarbenes.

Synthesis of 6-O-poly(ϵ-caprolactone)-L-ascorbic acid and its controlled release from supramolecular polymer micelles.

Lipophilic 6-O-poly (ϵ-caprolactone)-L-ascorbic acid (AA-6-PCL) is synthesized through ROP of ϵ-caprolactone (CL). The number of repeating CL units in the polymer chain varies from 6 to 19. AA-6-PCL loaded supramolecular polymer micelles (SMPMs) are constructed with β-cyclodextrin (β-CD) and PCL as blocks. Transmission electron microscopy images show a nanospheric morphology of the micelles with a size range of 43.3 ± 5.0 nm. The drug loading contents are 22.53-39.23% for AA-6-PCL. AA-6-PCL exhibits high radical scavenging capacity (93.96-96.73%) and efficient scavenging potency, and a cytotoxicity study proves the excellent cytocompatibility of AA-6-PCL loaded β-CD/PCL SMPMs, which altogether herald their potential application in the study of the induced pluripotent stem cells.