Cellulose Sulfates Research Articles

Sodium cellulose sulfate and its antimicrobial activity

Sodium cellulose sulfates were prepared in various degrees of substitution (DS) and degree of polymerization (DP) by directly sulfating cotton and microcrystalline cellulose. Molecular parameters of the prepared samples were characterized using elemental analysis, IR spectroscopy, and 13C NMR spectroscopy techniques. The antibacterial activities of the sodium cellulose sulfates were assayed against both gram-negative and gram-positive bacteria. The study examined the dependence of antimicrobial properties on molecular weight (Mw) and DS. The samples showed DS- and DP-dependent antibacterial activity against both gram-negative and gram-positive pathogenic microorganisms. Samples with DS ≥2.0 exhibited the highest antibacterial activity, indicating the presence of sulfate groups in C-2 and/or C-3 carbon atoms in cellulose anhydroglucose unit (AGU) induces the antibacterial activity. Additionally, SCS samples with DP around 340 showed the highest antibacterial activity against all species of bacteria. The mechanism of antimicrobial effect of SCS derivatives is most likely directed at the destruction of bacterial membranes.

Sulfation of Birch Wood Microcrystalline Cellulose with Sulfamic Acid Using Ion-Exchange Resins as Catalysts

Cellulose sulfates are important biologically active substances with a wide range of useful properties. The development of new methods for the production of cellulose sulfates is an urgent task. In this work, we investigated ion-exchange resins as catalysts for the sulfation of cellulose with sulfamic acid. It has been shown that water-insoluble sulfated reaction products are formed in high yield in the presence of anion exchangers, while water-soluble products are formed in the presence of cation exchangers. The most effective catalyst is Amberlite IR 120. According to gel permeation chromatography, it was shown that the samples sulfated in the presence of the catalysts KU-2-8, Purolit s390 plus, and AN-31 SO42- underwent the greatest degradation. The molecular weight destribution profiles of these samples are noticeably shifted to the left towards low-molecular-weight compounds with an increase in fractions in the regions Mw ~2.100 g/mol and ~3.500 g/mol, indicating the growth of microcrystalline cellulose depolymerization products. The introduction of a sulfate group into the cellulose molecule is confirmed using FTIR spectroscopy by the appearance of absorption bands at 1245-1252 cm-1 and 800-809 cm-1, which correspond to the vibrations of the sulfate group. According to X-ray diffraction data, amorphization of the crystalline structure of cellulose is observed during sulfation. Thermal analysis has shown that with an increase in the content of sulfate groups in cellulose derivatives, thermal stability decreases.

Facile sulfation of cellulose via recyclable ternary deep eutectic solvents for low-cost cellulose nanofibril preparation.

Here we present a new method to treat cellulose with a sulfamic acid-urea-choline chloride (ternary deep eutectic solvent) system, which can realize both swelling and sulfation of cellulose. This can greatly reduce the energy consumption in the process of cellulose nanoization, and use it to successfully prepare food packaging films for eliminating odors. We hope that due its simplicity and resource-efficiency, this method will have a widespread influence on currently used (nano) cellulose modification protocols.

Synthesis of Thermoresponsive PNIPAM-Grafted Cellulose Sulfates for Bioactive Multilayers via Layer-by-Layer Technique.

The robust thermoresponsive and bioactive surfaces for tissue engineering by combining poly-N-isopropylacrylamide (PNIPAM) and cellulose sulfate (CS) remain highly in demand but not yet realized. Herein, PNIPAM-grafted cellulose sulfates (PCSs) with diverse degrees of substitution ascribed to sulfate groups (DSS) are synthesized for the first time. Higher sulfated PCS2 generally forms larger aggregates than lower sulfated PCS1 at their cloud point temperatures (TCP) of around 33 °C, whereas PCS1 leads to larger aggregates at body temperature (37 °C). Via the layer-by-layer (LbL) technique, biocompatible polyelectrolyte multilayers (PEMs) composed of PCSs as polyanions in combination with poly-l-lysine (PLL) or quaternized chitosan (QCHI) as polycations were fabricated. The resulting surfaces contained a more intermingled structure of polyanions with both polycations, while higher sulfated cellulose derivatives (CS2 and PCS2) displayed greater stability. Studies on toxicity and biocompatibility of PEM using 3T3 mouse fibroblasts showed a lower cytotoxicity of PEM with PCS2 and CS2 than PCS1 and CS1. Furthermore, the PEM using PCS2 particularly in combination with QCHI demonstrated excellent biocompatibility that is promising for new bioactive, thermoresponsive coatings on biomaterials and substrata for culturing adhesion-dependent cells.

Sulfated Cellulose Nanofibrils from Chlorosulfonic Acid Treatment and Their Wet Spinning into High-Strength Fibers.

This paper presents the proof of concept for a facile sulfation-disintegration approach toward generating sulfated cellulose nanofibrils (SCNF) via direct sulfation of rice straw cellulose with chlorosulfonic acid (HSO3Cl) followed by blending. The direct sulfation of cellulose with chlorosulfonic acid (HSO3Cl) was optimized at acid ratios of 1-1.5 HSO3Cl per anhydroglucose unit (AGU) and short reaction times (30-60 min) at ambient temperature to produce SCNF with tunable charges of 1.0-2.2 mmol/g, all in impressively high yields of 94-97%. SCNF were characterized via AFM, TEM, FTIR, and XRD. SCNF lengths (L: 0.75-1.24 μm) and widths (W: 3.9-5.9 nm) decreased with harsher sulfation, while heights (H: 1.23-1.32 nm) remained relatively static. The SCNF had uniquely anisotropic cross sections (W/H: 3.0-4.7) and high aspect ratios (L/H: 568-984) while also exhibiting amphiphilicity, thixotropy, and shear thinning behaviors that closely followed a power law model. Aqueous SCNF dispersions could be wet spun into organic and mixed organic/ionic coagulants, producing continuous fibers possessing an impressively high tensile strength and Young's modulus of up to 675 ± 120 MPa and 26 ± 5 GPa, respectively.

Hydrogels Based on Oxidized Cellulose Sulfates and Carboxymethyl Chitosan: Studies on Intrinsic Gel Properties, Stability, and Biocompatibility

Cellulose and chitosan are excellent components for the fabrication of bioactive scaffolds, as they are biocompatible and abundantly available. Their derivatives Ocarboxymethyl chitosan (CMChi) and oxidized cellulose sulfate (oxCS) can form in situ gelling, bioactive hydrogels, due to the formation of imine bonds for crosslinking. Here the influence of the degrees of sulfation (DS), oxidation (DO), and the molecular weight of oxCS on intrinsic and rheological properties of such hydrogels and their ability to support the survival and growth of human-adipose-derived stem cells (hADSC) is investigated. It is found that the pH of the hydrogels is generally slightly acidic, while their network density and E-modulus are found to be dependent on the DS and DO, which makes the properties of hydrogels tunable. Extensive studies show that hydrogels can be stable for up to 14 days and that their stability is largely dependent on the DO, molecular weight, and the components mixing ratio. Cytotoxicity studies of the hydrogel with hADSCs show biocompatible gels in dependence on the molecular weight and degree of oxidation with viable cells up to 14 days. These findings can help to develop specifically tailored hydrogels for tissue engineering applications to replace different types of connective tissue.

Cellulose sulfate/EMIMAc solution: rheological properties and shaping into polyelectrolyte complexes for protein adsorption

Cellulose sulfates (CS) with low degree of substitution (DS) and high degree of polymerization (DP) were prepared via a controlled sulfation modification. The obtained CS with DS 0.42 and DP 293 showed an enhanced solubility of 14.7 g/100 g in the ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIMAc) compared to unmodified cellulose. The rheological study revealed that the CS/EMIMAc solution behaved as polymers in a θ solvent with the unique three-region flow curves under shear stress. It also showed a property of typical polyelectrolyte solution with the overlap concentration (c*) of 0.2 wt% and the entanglement concentration (ce) of 3.0 wt%, respectively. The CS/EMIMAc solution with a concentration of 5 wt% was selected to develop polyelectrolyte complex (PEC) with chitosan using extrusion-spherization and emulsification-solvent evaporation. The produced PEC beads and magnetic microspheres had an average size of 1.0 mm and 22.1 µm, respectively. The PEC microspheres showed greater absorption capability for bovine serum albumin than the beads with the maximum adsorption value of 780 mg/g.

Effective, low cytotoxic cell membranes protector based on amphiphilic conjugate of cellulose sulfate with isobornylphenol

Attaching alkylphenols to hydrophilic macromolecular matrices is an effective means to improve quality of the existing antioxidants and to create new antioxidants. In this work cellulose sulfates in the form of tetrabutylammonium salts was used as a basis for the synthesis of ether containing covalently bonded fragments of 2,6-diisobornyl-4-methylphenol in homogenous medium. Optimum conditions for the synthesis of amphiphilic macromolecules containing up to 6 mass% of hydrophobic terpenophenolic fragments were founded. Polymer structure was proved by the element analysis, UV, IR and NMR spectroscopy. Dynamic light scattering method was used to demonstrate the way the supramolecular assemblies are formed in the solutions of synthesized amphiphilic conjugate. Synthesized conjugates of cellulose sulfate with varying alkylphenols content are characterized by low cytotoxicity, as well as high antioxidant and membrane-protective activity in the biological model, increasing the survival rate of cells under acute oxidative stress. Amphiphilic conjugate in form of tetrabutylammonium salts of cellulose sulfate at low concentration turned out to be more effective than the conjugates of terpenophenols with sodium salts of cellulose sulfate.

Effect of Sulfation Route and Subsequent Oxidation on Derivatization Degree and Biocompatibility of Cellulose Sulfates.

Sulfated cellulose (CS) represents an interesting biopolymer due to bioactivity comparable to heparin. However, use of CS for making surface coatings or hydrogels requires the presence of reactive groups for covalent reactions. Here, an approach is presented to oxidize cellulose sulfates for subsequent cross-linking reactions with amino groups to form imine bonds. Cellulose is sulfated by direct sulfation or acetosulfation, followed by a Malaprade oxidation. The CS obtained is characterized by elemental analysis and 13 C-NMR spectroscopy. The resulting oxidized cellulose sulfates (oxCS) have different degrees of sulfation ranging from 0.79 to 1.13 and oxidation degrees from 0.18 to 0.34, but also different mass average molecular mass (MW ). Toxicity studies are carried out with mouse 3T3 fibroblasts exposed to aqueous solutions of oxCS. The results show that all oxCS are non-toxic at lower concentrations (0.5 mg mL-1 ), but with both increasing degree of oxidation and concentrations, toxic effects are observed particularly for acetosulfated and lesser for direct sulfated oxCS, which is related to a decrease in the MW of the products. It is concluded that oxCS obtained by direct sulfation with MW above 70 kDa may represent a biocompatible material for the applications suggested above.

Marine Pollution of Chemicals Detergents Contamination Induced Apoptosis and Necrosis in Fish Liver (Sardine aurita) by Flow Cytometry DNA Measurements

Background: Presently, there are wide uses of detergents, which discharged to marine environment (Mediterrean sea). Detergents are organic chemical compounds, consisting of fatty acids, and different components of Alkyl Benzene, Sulphonates, Polyphosphates, Cellulose, Sucrinic acid, and Sodium Lauryl Sulfates. Further, even if at low concentrations, the synthetic detergents are considered to be toxic to marine biodiversity. Since, these surfactants are not completely degraded by waste water treatment. It has ability to damage the DNA and accumulated on fish and other marine organisms. Methods: Flow cytometry technique was applied, because it’s accuracy for analysis of DNA contents. Hence, the present study evaluated the impact of sodium lauryl sulfate as synthetic detergent on the DNA of sardine fish as a marine biological indicator. Sardinella aurita was collected from clean and SLS-contaminated sites. The flow cytometry technique was employed to assess levels of active (apoptosis) and passive (necrosis) cell death in both exposed and unexposed fishes to SLS. Result: Chemical detergent contains 120 ml (i.e., 20mg/L) of sodium lauryl sulfates. The result shows more distinct and significant differences of the early and late apoptosis/ necrosis of Sardine fish liver, compared with unexposed fish samples from cleaned reference site. Conclusions: The present data indicate that SLS was able to cause toxicity to fish. Data recorded revealed that toxicity as a significant accumulation of hepatic tissue cellular DNA during the G0-G1 in a significant way (P<0.05), compared with that of unexposed liver tissue. In the same way, there was an insignificant accumulation of hepatic cell’s DNA in the S phase but not during the G2/M phase, finally there was a significant arrest / DNA accumulation during the PreG1- phase (P<0.05). In the meantime, accompanies of apoptotic profile of cells exposed to SLS showed a significant total apoptotic form significantly elevated compared with reference site.

Homogenous synthesis of sodium cellulose sulfates with regulable low and high degree of substitutions with SO3/Py in N,N-dimethylacetamide/LiCl

Synthesis possibility of cellulose sulfates with a low and high degree of substitution (DS) by direct homogenous sulfation of cotton cellulose in N,N-dimethylacetamide/lithium chloride (DMA/LiCl) using SO3/pyridine (Py) complex was studied comprehensively. The sulfation reactions were carried at different temperatures, time durations, amount of the sulfating reagent and celluloses with varying weight average degree of polymerization (DPw). It was found that the method is very appropriate to prepare sodium cellulose sulfate (SCS) with low and high DS from celluloses having wide range DPw. Completely water-soluble SCS samples with regulable DS values from 0.23 to 2.56 were obtained. Suitable conditions were proposed to gain high sulfate content and the samples with DS values of 2.16–2.32, and yield of 69.4–77.8% could be prepared in these conditions. Celluloses with low and high DPw values exhibited similar reactivity for sulfation. Precipitation of the product and drastic depolymerization in the polymer chain have not occurred during the reaction.

Development of hydrogels based on oxidized cellulose sulfates and carboxymethyl chitosan

Cellulose or chitosan represent highly abundant biopolymers possessing excellent biocompatibility that is required in tissue engineering. Both, cellulose and chitosan can be used to form hydrogels that can replace soft human tissues like cartilage. Hence, we developed here an approach to oxidize cellulose after sulfation, which was then crosslinked with carboxymethyl chitosan (CMCh). Sulfation was performed either by direct or acetosulfation reaching different sulfation degrees of DSSulf = 0.8–2.0. Subsequently oxidation of cellulose sulfate (CS) was performed with sodium periodate, which yielded aldehyde contents of DSAld = 0.1–0.3. Since oxidation requires the presence of vicinal hydroxyl groups in the anhydroglucose unit (AGU) of CS, higher sulfation degree as obtained by direct sulfation including hydroxyl groups at C2 and C3-position yielded lower aldehyde contents. On the contrary, regioselective sulfation at C6-position by acetosulfation was more suitable to achieve higher oxidation degrees of CS. Consequently, hydrogel formation obtained by chemical crosslinking of oxidized cellulose sulfate (oCS) with CMCh was fast within seconds when oxidation degree was high, but sulfation degree low. Moreover gel formation lasted almost 24 h when sulfation degree was high. It could also be shown that hydrogels based on oCS with a DSAld of 0.28 or higher were stable for 25 days when incubated in phosphate-buffered saline (PBS) or Dulbeccos modified Eagle medium (DMEM). Studies with pH dependent fluorescent tracer molecules could show that the intrinsic pH value in hydrogels was slightly acidic (sim pH 6.4) when they were incubated in PBS at pH 7.4. Mass transfer and homogeneity of the gel network was studied by NMR finding that diffusion of water molecules was not hindered inside the hydrogels.

Direct sulfation of cellulose fibers using a reactive deep eutectic solvent to produce highly charged cellulose nanofibers

Wood cellulose pulp was sulfated using a reactive deep eutectic solvent (DES). DES was prepared by heating sulfamic acid and urea together at 80 °C at a molar ratio of 1:4, 1:3, or 1:2. Sulfation of cellulose was performed by mixing dry cellulose fibers with DES at 80 °C, followed by heating at 150 °C for half an hour. Anionic charge as high as 3 mmol/g (degree of substitution of 0.68) was obtained with this simple chemical modification of cellulose at an elevated temperature using DES both as reaction media and reagent without any external solvent. The decrease in the urea content of DES improved the sulfation efficiency. In addition, the presence of urea led to the carbamation of cellulose to some extent. Cellulose sulfate (charge of 2.40 mmol/g) became a gel-like material in water, and after passing once through a microfluidizator, a highly transparent nanocellulose gel (transmittance of 0.1% solution at a visible light range was over 95%) was obtained. Sulfated cellulose nanofibers (SCNFs) exhibited a width of around 4 nm with a minor presence of elemental fibril aggregates (containing five or less elemental fibrils). SCNFs with high aspect ratio can have a potential end-use as a rheology modifier because of their high viscosity even at low concentrations or act as reinforcing additives.Graphical abstract

Synthesis and Study of Copper-Containing Polymers of Microcrystalline Cellulose Sulfates from Larch Wood

For the first time, the synthesis of water-soluble copper-containing microcrystalline cellulose sulfates (Сu-MCS) has been performed by the ion exchange method. The composition of the products has been studied by chemical methods and X-ray spectral microanalysis. The copper content in the Сu-MCS samples was 12.6–14.1%. The absence of sodium in the resulting polymer indicates the complete substitution of the sodium cations by the copper cations in the sodium salt of MCC sulfate. The structure of the copper-containing sulfates of microcrystalline cellulose has been confirmed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and electron paramagnetic resonance (EPR). According to the XRD method, Сu-MCS and Na-MCS have an amorphous structure in contrast to the original MCC samples, which have a high degree of crystallinity. The EPR data have demonstrated the formation of a pseudocrystalline structure of the copper-containing salt system in the Сu-MCS samples. As shown by atomic-force microscopy, the surface of the Сu-MCS films consists of homogeneous crystallites, which have a spherical or slightly extended form with the size of about 70 nm. The film surface is quite homogeneous in its phase composition and contains no impurities.

Influence of Regioselectively Sulfated Cellulose on in Vitro Vascularization of Biomimetic Bone Matrices.

Vascularization is essential for the regeneration of bone tissue within composite material. We measured the effect of regioselectively modified cellulose/hemicellulose as an additive for porous scaffolds of collagen/hydroxyapatite nanocomposite on the tubule formation of human vascular endothelial cells. Using a coculture of endothelial cells and fibroblasts, endothelial cells formed a network of tubules within an incubation time of 14 to 24 days. A cellulose sulfate with irregular sulfation pattern along the polysaccharide backbone (13-TACS-01) led to an additional increase in vascular endothelial growth factor (VEGF)-induced tubule formation, as observed in an in vitro angiogenesis assays. In contrast with structurally different heparin, these cellulose sulfates have no apparent affinity to VEGF. Their impact on endothelial function may possibly be due to interactions with cell surface receptors/soluble factors not yet defined.

Integration of peroxide delignification and sulfamic acid sulfation methods for obtaining cellulose sulfates from aspen wood

A new method to obtain cellulose sulfates from available and inexpensive raw material—aspen wood was developed. This method integrates catalytic peroxide delignification and sulfamic acid sulfation stages. Solvents such as acetic acid and water were used for isolation of pure cellulose by wood peroxide delignification with TiO2 catalyst. Low-aggressive and less-toxic sulfating agent—sulfamic acid–urea mixture was used to obtain cellulose sulfates.

Preparation of sodium cellulose sulfate oligomers by free-radical depolymerization

Sodium cellulose sulfates with various degree of substitution (DS) and degree of polymerization (DP) were synthesized by homogeneous sulfation of cellulose with different DP by using SO3/pyridine (Py) complex in N,N-dimethylacetamide/lithium chloride (DMA/LiCl). Sodium cellulose sulfate (SCS) samples obtained were free-radically depolymerized with hydrogen peroxide and copper (II) acetate at a controlled pH value of 7.5–8.0 and without control of the pH value (pH 2.5–4.0). The depolymerization process was studied with respect to changes in molecular mass, total DS, and substituent distribution of SCS. Elemental analysis, 13C NMR- and IR spectroscopic methods indicated that primary structures of SCS were retained with insignificant decreases in total sulfate content in the depolymerization. The depolymerization of SCS was randomly and obeyed pseudo first order kinetics under the conditions applied. SCS oligomers with low DP and very narrow molecular weight distribution were prepared by the depolymerization at pH 2.5–4.0.

Polyelectrolyte Complex Based Interfacial Drug Delivery System with Controlled Loading and Improved Release Performance for Bone Therapeutics

An improved interfacial drug delivery system (DDS) based on polyelectrolyte complex (PEC) coatings with controlled drug loading and improved release performance was elaborated. The cationic homopolypeptide poly(l-lysine) (PLL) was complexed with a mixture of two cellulose sulfates (CS) of low and high degree of substitution, so that the CS and PLL solution have around equal molar charged units. As drugs the antibiotic rifampicin (RIF) and the bisphosphonate risedronate (RIS) were integrated. As an important advantage over previous PEC systems this one can be centrifuged, the supernatant discarded, the dense pellet phase (coacervate) separated, and again redispersed in fresh water phase. This behavior has three benefits: (i) Access to the loading capacity of the drug, since the concentration of the free drug can be measured by spectroscopy; (ii) lower initial burst and higher residual amount of drug due to removal of unbound drug and (iii) complete adhesive stability due to the removal of polyelectrolytes (PEL) excess component. It was found that the pH value and ionic strength strongly affected drug content and release of RIS and RIF. At the clinically relevant implant material (Ti40Nb) similar PEC adhesive and drug release properties compared to the model substrate were found. Unloaded PEC coatings at Ti40Nb showed a similar number and morphology of above cultivated human mesenchymal stem cells (hMSC) compared to uncoated Ti40Nb and resulted in considerable production of bone mineral. RIS loaded PEC coatings showed similar effects after 24 h but resulted in reduced number and unhealthy appearance of hMSC after 48 h due to cell toxicity of RIS.

Изучение сульфатов микрокристаллической целлюлозы, полученных с использованием хлорсульфоновой и сульфаминовой кислот

Composition and structure of microcrystalline cellulose (MCC) sulfates obtained by traditional and new advanced methods of MCC sulfation were compared. Data on the composition and structure of MCC sulfates synthesized in the medium of chlorosulfonic acid –1,4-dioxane and by sulfation of MCC with sulfamic acid in the presence of urea in N,N-dimethylformamide and diglyme were obtained with the use of elemental analysis, FTIR, Raman, 13C NMR, XRD, XPS, SEM and AFM methods. It was shown that MCC sulfates synthesized by new methods have more homogeneous composition and morphology as compared to sulfates obtained by known methods.

Study of cellulose sulfates by X-ray photoelectron spectroscopy

Samples of microcrystalline cellulose (MCC) have been studied by X-ray photoelectron spectroscopy before and after sulfation. It has been found that the reaction of MCC with chlorosulfonic acid in dioxane results in the incorporation of sulfate groups into the structure of cellulose. The content of sulfur in sulfated MCC varies from 4.0 to 9.7 at %, sulfur being in the form of sulfate. The sulfur content on the surface and in the bulk of MCC sulfate samples has been compared. The difference in the shape of 1s lines of carbon in the spectra of initial and sulfated MCC samples indicates that the electron state of a fraction of the carbon atoms undergoes changes during sulfation.