Synthesis,Characterization and Biospecific Degradation Behavior of Sulfated Chitin

Chitin is a polysaccharide found in the outer skeleton of insects, crabs, shrimps, and lobsters and in the internal structures of other invertebrates. Sulfated chitin was prepared by reacting carboxymethyl chitin (CM-chitin) with 2-aminoethane sulfonic acid by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) catalyst. The prepared sulfated chitin was characterized by FTIR, elemental analysis, thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The degree of substitution was found to be 0.98 by elemental analysis. The TGA studies showed that sulfated chitin was less thermal stability than carboxymethyl chitin. This is due to the grafting reaction. The sulfated chitin membranes were prepared from sulfated chitin and then crosslink with glutaradehyde. The biodegradation process was performed in PBS (pH 7.4) containing lysozyme (10 µg/ml) at 37 °C in an incubator. Experimental results from weight loss throughout the study showed that the biospecific degradation occur on the membrane by lysozyme.     

Pyranoside‐into‐Furanoside Rearrangement: New Reaction in Carbohydrate Chemistry and Its Application in Oligosaccharide Synthesis

Great interest in natural furanoside‐containing compounds has challenged the development of preparative methods for their synthesis. Herein a novel reaction in carbohydrate chemistry, namely a pyranoside‐into‐furanoside (PIF) rearrangement permitting the transformation of selectively O‐substituted pyranosides into the corresponding furanosides is reported. The discovered process includes acid‐promoted sulfation accompanied by rearrangement of the pyranoside ring into a furanoside ring followed by solvolytic O‐desulfation. This process, which has no analogy in organic chemistry, was shown to be a very useful tool for the synthesis of furanoside‐containing complex oligosaccharides, which was demonstrated by synthesizing disaccharide derivatives α‐D ‐Galp‐(1→3)‐β‐D ‐ Galf ‐OPr, 3‐O‐s ‐lactyl‐β‐D ‐ Galf ‐(1→3)‐β‐D ‐Glcp‐OPr, and α‐L ‐ Fucf ‐(1→4)‐β‐D ‐GlcpA‐OPr related to polysaccharides from the bacteria Klebsiella pneumoniae and Enterococcus faecalis and the brown seaweed Chordaria flagelliformis.     

Putting Electrospun Nanofibers to Work for Biomedical Research

Electrospinning has been exploited for almost one century to process polymers and related materials into nanofibers with controllable compositions, diameters, porosities, and porous structures for a variety of applications. Owing to its high porosity and large surface area, a non‐woven mat of electrospun nanofibers can serve as an ideal scaffold to mimic the extracellular matrix for cell attachment and nutrient transportation. The nanofiber itself can also be functionalized through encapsulation or attachment of bioactive species such as extracellular matrix proteins, enzymes, and growth factors. In addition, the nanofibers can be further assembled into a variety of arrays or architectures by manipulating their alignment, stacking, or folding. All these attributes make electrospinning a powerful tool for generating nanostructured materials for a range of biomedical applications that include controlled release, drug delivery, and tissue engineering.

     

Chemical Hemisynthesis of Sulfated Cyanidin-3-O-Glucoside and Cyanidin Metabolites

The metabolism of anthocyanins in humans is still not fully understood, which is partly due to the lack of reference compounds. It is known that sulfation is one way of the complex phase II biotransformation mechanism. Therefore, cyanidin-3-O-glucoside and the cyanidin aglycone were chemically converted to their sulfates by reaction with sulfur trioxide-N-triethylamine complex in dimethylformamide. The reaction products were characterized by UHPLC coupled to linear ion trap and IMS-QTOF mass spectrometry. Based on MS data, retention times, and UV-Vis spectra, the compounds could tentatively be assigned to A-, C-, or B-ring sulfates. Analysis of urine samples from two volunteers after ingestion of commercial blackberry nectar demonstrated the presence of two sulfated derivatives of the cyanidin aglycone and one sulfated derivative of the cyanidin-3-O-glucoside. It was found that both the A ring and the B ring are sulfated by human enzymes. This study marks an important step toward a better understanding of anthocyanin metabolism.     

Sulfated and Non‐Sulfated Glycopeptide Recognition Domains of P‐Selectin Glycoprotein Ligand 1 and their Binding to P‐ and E‐Selectin

Total synthesis through block glycosylation and selective chemical O‐sulfation of tyrosine residues yielded the glycopeptide recognition domain A (X=SO₃^?) of the P‐selectin glycoprotein ligand 1, in which the terminal sialic acid of the complex hexasaccharide side chain was replaced by (S)‐cyclohexyl lactic acid. In binding assays the O‐sulfated structure A showed high affinity towards P‐selectin, the non‐sulfated towards E‐selectin.

     

New Methods for the Synthesis of Imidazoline-N-Oxides

Δ³-lmidazoline-3-oxides were prepared by the reaction of corresponding aromatic Schiff bases with syn-2-bromoacetophenone oxime. 5,6-Dihydro-4H-1,2,5-oxadiazines were isolated as byproduct in some instances.     

Iridium-Catalyzed C5-Regioselective Esterification of Dienyl Alcohols with Carboxylic Acids

One-step process for the preparation of a 1,3-dienyl-5-ester motif from readily available substrate remains a challenging work in organic synthesis. We herein report the first example of C5-regioselective esterification of unactivated dienyl alcohols, using free carboxylic acids as nucleophiles under mild conditions, providing a series of 1,3-dienyl-5-ester compounds in excellent regioselectivity and E-selectivity.     

Hyaluronan/Collagen Hydrogels with Sulfated Hyaluronan for Improved Repair of Vascularized Tissue Tune the Binding of Proteins and Promote Endothelial Cell Growth

Innovative biomaterial‐based concepts are required to improve wound healing of damaged vascularized tissues especially in elderly multimorbid patients. To develop functional hydrogels as 3D cellular microenvironments and as carrier or scavenging systems, e.g., for mediator proteins or proinflammatory factors, collagen fibrils are embedded into a network of photo‐crosslinked acrylated hyaluronan (HA), chondroitin sulfate (CS), or sulfated HA (sHA). After lyophilization, the gels show a porous structure and an improved stability against degradation via hyaluronidase. Gels with CS and sHA bind significantly more lysozyme than HA/collagen gels and retard its release. The proliferation and metabolic activity of endothelial cells are significantly increased on sHA gels compared to CS‐ or only HA‐containing hydrogels. These findings highlight the potential of HA/collagen hydrogels with sulfated glycosaminoglycans to tune the protein binding and release behavior and to directly modulate cellular response. This can be easily translated into biomimetic biomaterials with defined properties to stimulate wound healing.     

Regioselectively Modified Cellulose and Chitosan Derivatives for Mono- and Multilayer Surface Coatings of Hemocompatible Biomaterials

In this study different synthetic strategies were developed and applied to introduce solely or in combination heparin/heparansulfate-like functional groups such as N-sulfo, O-sulfo, N-acetyl, and N-carboxymethyl groups into chitosan and cellulose with highest possible regioselectivity and completeness and defined distribution along the polymer chain. Completely substituted 6-amino-6-deoxycellulose and related derivatives were prepared from tosylcellulose (DS 2.02; C₆ 1.0) by nucleophilic substitution with azido groups only in the 6-position at 50 °C with subsequent reduction to amino groups and completely removing tosyl groups in the 2,3-position. 2,6-Di-O-sulfocellulose was prepared using the reactivity difference between C-2, C-6 and C-3 of cellulose. The reactivity difference between amino groups and hydroxyl groups was used to prepare various N-substituted derivatives. Partially 2,6-di-O-sulfated cellulose was obtained from trimethylsilylcellulose by the insertion of sulfurtrioxide into the Si–O ether linkage. Partially 3-O-sulfocellulose was synthesized by protecting C-2 and C-6 with trifluoroacetyl groups. A copper–chitosan complex was used to synthesize 6-O-sulfochitosan with a DS of 1.0 at C-6 and various partially 6-O-desulfonated products are possible. Using the phthalimido group to increase the solubility of chitosan in DMF, the regioselectivity of 3-O-sulfo groups was improved by regioselective 6-O-desulfonation of nearly complete 3,6-O-disulfochitosan. The platelet adhesion properties of immobilized regioselectively modified water-soluble derivatives on membranes have been tested in vitro. Some regioselectively modified chitosan and cellulose derivatives are potential candidates for the surface coatings of biomaterials if the regioselective reactions are somewhat further optimized.     

Self‐Assembled Gels for Biomedical Applications

Natural and synthetic gel‐like materials have featured heavily in the development of biomaterials for wound healing and other tissue‐engineering purposes. More recently, molecular gels have been designed and tailored for the same purpose. When mixed with, or conjugated to therapeutic drugs or bioactive molecules, these materials hold great promise for treating/curing life‐threatening and degenerative diseases, such as cancer, osteoarthritis, and neural injuries. This focus review explores the latest advances in this field and concentrates on self‐assembled gels formed under aqueous conditions (i.e., self‐assembled hydrogels), and critically compares their performance within different biomedical applications, including three‐dimensional cell‐culture studies, drug delivery, and tissue engineering. Although stability and toxicity issues still need to be addressed in more detail, it is clear from the work reviewed here that self‐assembled gels have a bright future as novel biomaterials.     

丙烯酸十八酯的合成新方法

以十八醇和丙烯酸为原料,在不加带水剂的条件下合成了丙烯酸十八酯。用正交实验确定了最佳合成工艺：十八醇108g(0．4mol),n(十八醇)：n(丙烯酸)=1．0：1．2,对甲苯磺酸1．0％(催化剂,以醇酸总质量计),对苯二酚0．7％(阻聚剂,以醇酸总质量计),反应温度135℃,反应时间6h,酯化率在92％以上。产物结构经元素分析,IR和^1H NMR表征。     

Synthesis of New Estrone Derivatives Using Excess Oxalyl Chloride

The synthesis and structure elucidation of three new estrone derivatives chloro-oxo-acetic acid (estra-1,3,5(10)-trien-17-on-3-yl methyl) ester (2), oxalic acid mono (estra-1,3,5(10)-trien-17-on-3-yl methyl) ester (3), and ethyl (3-methoxyestra-1,3,5(10)-trien)-17-yl oxalate (5) have been described.     

The basic research on physiological property of functionalized hyaluronan—I. Effect of hyaluronan and sulfated hyaluronan on cell proliferation of human epidermal keratinocytes

Hyaluronan (HA) is one of the polysaccharides that is found widely in connective tissue of mammals, and it has no sulfate group and high molecular weight in comparison with other glycosaminoglycans. Glycosaminoglycans are deeply concerned with the manifestation of biofunctions not only by their physical properties but also by physiological ones. In this study, sulfated HA (S‐HA) with various degrees of sulfate substitution and high molecular weight will be synthesized in order to give HA new biological functions. Moreover, the effect of HA and S‐HA on cell proliferation of human epidermal keratinocytes in vitro will be discussed. HA did not affect lag phase, but growth rate (metabolic turnover) of the cell in a logarithmic growth phase which was controlled by the molecular weight of HA. S‐HA stimulated the cell proliferation in the low concentration region under 1 μg/ml. While it inhibited the cell proliferation in the high concentration region over 10 μg/ml. It strongly suppressed the cell proliferation in the logarithmic growth metaphase. These facts were considered to be caused by the change of the cell‐matrix and/or cell–cell interactions. Copyright © 2004 John Wiley & Sons, Ltd.     

Modified Hyaluronan Hydrogels Support the Maintenance of Mouse Embryonic Stem Cells and Human Induced Pluripotent Stem Cells

These studies provide evidence for the ability of a commercially available, defined, hyaluronan‐gelatin hydrogel, HyStem‐C?, to maintain both mouse embryonic stem cells (mESCs) and human induced pluripotent stem cells (hiPSCs) in culture while retaining their growth and pluripotent characteristics. Growth curve and doubling time analysis show that mESCs and hiPSCs grow at similar rates on HyStem‐C? hydrogels and mouse embryonic fibroblasts and Matrigel?, respectively. Immunocytochemistry, flow cytometry, gene expression and karyotyping reveal that both human and murine pluripotent cells retain a high level of pluripotency on the hydrogels after multiple passages. The addition of fibronectin to HyStem‐C? enabled the attachment of hiPSCs in a xeno‐free, fully defined medium.

     

Microwave‐Assisted Hydrogel Synthesis: A New Method for Crosslinking Polymers in Aqueous Solutions

It has been found that hydrogels may be formed by microwave irradiation of aqueous solutions containing appropriate combinations of polymers. This new method of hydrogel synthesis yields sterile hydrogels without the use of monomers, eliminating the need for the removal of unreacted species from the final product. Results for two particularly successful combinations, poly(vinyl alcohol) with either poly(acrylic acid) or poly(methylvinylether‐alt‐maleic anhydride), are presented. Irradiation using temperatures of 100–150 °C was found to yield hydrogels with large equilibrium swelling degrees of 500–1000 g g⁻¹. Material leached from both types of hydrogel shows little cytotoxicity towards HT29 cells.     

Xylan‐Based Nanoparticles: Prodrugs for Ibuprofen Release

Esterification of xylan with ibuprofen via activiation of the carboxylic acid with N,N′‐carbonyldiimidazole (CDI) yields products of high drug loadings. Subsequent sulfation of xylan ibuprofen esters using the gentle agent SO₃/DMF was successfully carried out in order to modify hydrophobicity of the xylan esters. The structure of the novel xylan esters was evaluated by means of NMR spectroscopy. The resulting xylan derivatives self assemble into spherical nanoparticles with mean diameters ranging from 162 to 472 nm. Preliminary stability measurements indicate that hydrolytic stability decreases with increase in degree of substitution of sulfate groups. Thus, a new concept toward improved drug delivery from polysaccharide‐based nanoparticles can be established here.