Molar Degree Of Substitution Research Articles

Remarkable rheological properties of short alkyl chain derivatives of hyaluronic acid

Event Abstract Back to Event Remarkable rheological properties of short alkyl chain derivatives of hyaluronic acid Dalila Petta1, 2, David Eglin1, Dirk W. Grijpma2 and Matteo D'Este1 1 AO Research Institute Davos, Switzerland 2 University of Twente, Department of Biomaterials Science and Technology, Netherlands Introduction: Chemical modification of hyaluronic acid (HA) is a key aspect for the production of advanced naturally derived biomaterials. The grafting of hydrophobic moieties to HA is of particular interest to generate amphiphilic species that can self-assemble in supramolecular structures[1]. In this study, we prepared and characterized a series of short alkyl derivatives of HA with a broad range of substitution degree (DS). A novel derivatization method based on amidation promoted by 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) was used[2]. Remarkable rheological properties were observed. Materials and Methods: HA-butylamine (HA-B) and HA-propylamine (HA-P) were synthesized by reacting HA (molecular weight = 280 kDa) with the amines in presence of DMTMM in MES buffer, pH = 5.5, at different temperatures, molar ratios between reagents and multiple feeding. The molar degree of substitution (DS) was determined via 1H NMR (Bruker Avance AV-500 18 MHz spectrometer). Flow and oscillatory rheological measurements were performed for 5% v/w solutions of HA-B and HA-P with an Anton Paar MCR-302 rheometer. As some derivatives were non-soluble, a thermal treatment (92°C for 1h 30', sufficient to make them soluble) was applied to all specimens before characterization. Absence of free amine groups in the final product was assessed via Ninhydrin assay. Results: Synthesis. At higher temperature, DMTMM was deactivated faster. Also the coupling proceeded faster, with overall yield increase (fig 1). DS of up to 51% was achieved with multiple amine additions. Rheological properties. Storage modulus G' increased with the increase of DS up to a maximum at DS = 3.7% (HA-B) and 3% (HA-P), and decreased for higher DS (fig 2). Similar behavior was observed for the viscosity curve (not shown), with maximum zero-shear viscosity and shear-thinning gradient for the DS above indicated. Fig. 1: Kinetics of HA-P formation at 56°C and at room temperature (RT), also upon multiple amine additions (empty squares). Fig. 2: G' at RT versus DS (ratio HA:DMTMM: amine 1:1:0.5). Discussion: A broad range of HA modifications with grafted short alkyl groups was achieved. Upon changing the DS values, remarkable changes in the rheological properties were observed. The complex dependence of G' on DS suggests a structural rearrangement with associative behaviour maximized at DS= 3.7% (HA-B) and 3% (HA-P). The non-solubility of most as-prepared derivatives before thermal treatment supports this hypothesis. At the moment, deeper structural analyses are ongoing. Conclusion: The DMTMM grafting strategy introduced here is a viable method for fine-tuning the rheological properties of HA with minimal modification of the polymer. Synthesis conditions were optimized, resulting in superior efficiency at high temperature despite faster DMTMM deactivation. Owing to their singular rheological profile, HA-B and HA-P are valuable biomaterial candidates for preparing bio-inks or hydrogels for drug delivery and regenerative medicine. Ms. Doris Sutter from ETH-Zurich, for performing NMR measurements

疏水改性玉米淀粉合成研究

本文以玉米淀粉为原料，烷基缩水甘油醚(AGE)为疏水化试剂，氢氧化钠作催化剂，水为溶剂，在较温和反应条件下合成了2-羟基-3-烷氧基丙基淀粉(AHPS)。考察了反应时间、反应温度对取代度和反应效率的影响，确定了最佳反应温度为75℃，最佳反应时间为5 h。用IR、1HNMR对产物结构进行了表征。 2-Hydroxy-3-alkoxypropyl starches (AHPS) were synthesized by an environmentally-friendly process using alkyl glycidyl ether (AGE) as hydrophobic reagent, water as solvent and sodium hy-droxide as catalyst. Effects of reaction time and reaction temperature on molar substitution degree and react efficiency were studied. The optimized reaction time is 5 h and the optimized reaction temperature is 75˚C. IR and 1HNMR were used to analyze the structure of modified products.

Clinical use of hydroxyethyl starch and serious adverse effects: Need for awareness amongst the medical fraternity

Clinical use of hydroxyethyl starch and serious adverse effects: Need for awareness amongst the medical fraternity

Effects of acid-hydrolysis and hydroxypropylation on functional properties of sago starch

In this study, sago starch was hydrolyzed by 0.14M HCl for 6, 12, 18, and 24h, and then modified by propylene oxide at a concentration of 0–30% (v/w). The effects of hydrolysis and etherification on molecular weight distribution, physicochemical, rheological, and thermal properties of dually modified starch were estimated. Acid hydrolysis of starch decreased the molecular weight of starch especially amylopectin, but hydroxypropylation had no effect on the molecular weight distribution. The degree of Molar substitution (DS) of hydroxypropylated starch after acid hydrolysis ranged from 0.007 to 0.15. Dually modified starch with a DS higher than 0.1 was completely soluble in cold water at up to 25% concentration of the starch. This study shows that hydroxypropylation and hydrolysis have synergistic effects unlike individual modifications. Dually modified sago starch can be applied to dip-molding for food and pharmaceutical processing because of its high solubility and low tendency for retrogradation.

Effects of Structural Modifications on Physicochemical and Bile Acid-Binding Properties of Psyllium

The effects of sulfation, hydroxypropylation, and succinylation on gelling, water uptake, swelling, and bile acid-binding capacities of psyllium were examined and compared at the same molar substitution degree. Sulfated, hydroxypropylated, and succinylated psyllium were prepared with substitution levels of 1.02, 0.88, and 0.79, respectively, and their structures were characterized using FT-IR, SEM, and ζ-potential determination. All three derivatization methods reduced the gelling and swelling capacities of psyllium and increased the water uptake and bile acid-binding capacities compared to the original psyllium. Interestingly, it was observed for the first time that introduction of a stronger negatively charged group into the molecule might more effectively enhance the bile acid-binding capacity of psyllium. On the other hand, the steric effect of the substitution groups seemed to be more critical in altering the gelling and swelling properties of psyllium.

Homogeneous synthesis of hydroxypropyl guar gum in an ionic liquid 1-butyl-3-methylimidazolium chloride

With potassium hydroxide (KOH) as catalyst, hydroxypropyl guar gum (HPG) was successfully prepared under homogenous conditions in an ionic liquid 1-butyl-3-methylimidazolium chloride (BmimCl). The value of degree of molar substitution (MS) of HPG, which was determined by means of 1H NMR, was easily controlled by varying the mass ratio of propylene oxide (PO) to guar gum (GG). The distribution of hydroxypropyl moieties among the seven hydroxy groups in HPGs was investigated by NMR and the results indicated that the homogeneous reaction preferentially substituted at the C3OH of the mannosyl residues in guar gum which was quite different from the heterogeneous reaction where substitution mostly occurred at C6OH. The average number of hydroxypropyl units per OH substitution of HPGs with MS value of 0.20, 0.37 and 0.60 was 1.82, 1.42 and 1.76, respectively.

One-step synthesis of glucose-branched galactomannan

The synthesis of branched polysaccharides using naturally occurring materials has been reported since 1975, but applications of branched polysaccharides are relatively limited because of the long and complex modification processes. In this work, a practical and efficient procedure is presented that in one step levoglucosan can be grafted to galactomannan (at 115°C for 15h) with monochloroacetic acid as catalyst. The structural characteristics of the resulting substances were investigated by NMR spectroscopy. The MS (molar degree of substitution) of glucose was shown to gradually increase with the increase of the ratio of levoglucosan to galactomannan, and the maximal MS is 0.6. Levoglucosan units are mostly grafted to the C6–OH of the galactosyl residues in galactomannan, and the maximal percentage of the substituted C6–OH of galactosyl residues is 42.2%. The resulting levoglucosan tended to graft to the branching glucosyl residues of copolymers with an increase in MS, and the average length of the branching glucose is 3.6 when MS is 0.6.

Properties of spruce sulfite pulp and birch kraft pulp after sorption of cationic birch xylan

In this study, correlations between the charge density of adsorbed cationic xylans and the mechanical properties of selected pulps are discussed. Hand-sheet experiments were carried out using birch sulfate pulp and spruce sulfite pulp after the adsorption of 2-hydroxypropyl-trimethylammonium-4-O-methylglucuronoxylans (HPMAGXs) with different molar degrees of substitution (MS) in the range of 0.06–0.19. The charge density of the HPMAGX in water was determined by polyelectrolyte titration. Properties such as the tensile and burst index increased after HPMAGX addition and showed an optimum depending on the MS, which was 0.1 for both pulps. Other properties like the tear-index or the specific volume changed depending on the pulp. Beating experiments were also performed and showed an increasing tensile index of birch kraft pulp in the range of 53.7 to 85.7 N m g−1 for a beating time of 10 min. The adsorption of HPMAGXs with different MS onto thiol-based self-assembled monolayers (SAMs) on gold and regenerated cellulose surfaces were studied using surface plasmon resonance (SPR). Electrostatic interactions were found to be the most important factors affecting HPMAGX adsorption, and a strong correlation between HPMAGX adsorption onto carboxyl-terminated SAMs (SAM-COOH) and paper strength when HPMAGX was used as a papermaking additive was observed.

Solubilization of ibuprofen with β-cyclodextrin derivatives: Energetic and structural studies

The aim of this work was to investigate the complexation of ibuprofen as model drug with various β-cyclodextrins (native β-cyclodextrin, hydroxypropyl-β-cyclodextrin with two different molar degrees of substitution, and methyl-β-cyclodextrin). Solutions of the commercially available β-cyclodextrins were prepared in phosphate buffer (73 mM). The pH value was adjusted to 7.4 and the solutions were isotonized with NaCl. A solution of ibuprofen was prepared in the same way. A thermal activity monitor was used for isothermal titration calorimetry (ITC). 1H NMR analysis was employed to investigate the structures of the complexes. ITC analysis showed that each type of β-cyclodextrin had its characteristic values of both enthalpy and mass equilibrium constant for the complexation processes with the drug molecules. 1H NMR spectroscopy of the complexes showed through significant differences in chemical shifts that the physical interaction between the cyclodextrins and ibuprofen molecules were also different, probably due to different three-dimensional arrangements of ibuprofen in the cyclodextrin cavity, induced by the different substituents bonded to the glucose rings. These differences were connected to the thermodynamic parameters of the complexes.

Interactions of ionic liquids with polysaccharides 9. Hydroxyalkylation of cellulose without additional inorganic bases

Water-soluble hydroxyalkyl cellulose with a molar degree of substitution of up to 2.79 was prepared under completely homogeneous reaction conditions in various ionic liquids without addition of inorganic bases. In acetate containing solvents the IL acts as a catalyst. The substitution patterns of the cellulose ethers were analyzed by 13C NMR spectroscopy, 1H NMR spectroscopy after peracetylation and GLC/MS after permethylation and depolymerization. A diminished tendency towards the formation of side chains compared to heterogeneously prepared hydroxyalkyl celluloses in the presence of inorganic bases was found.

Interfacially Assembled Carbohydrate Nanocapsules: A Hydrophilic Macromolecule Delivery Platform

A prospective approach was used to synthesize carbohydrate nanocapsules with a macromolecule payload and suitable interfacial properties for in vivo systemic circulation. Spatially directed carbohydrate assembly and polymerization resulted in structured hydrophilic vesicles with diameters of 200-300 nm. Mononucleated dispersions with monodisperse distributions were demonstrated in aqueous vehicles. The effects of pH, buffer capacity and reaction time on the molar degree of substitution of terephthaloyl chloride, trimesoyl chloride, and diethylmalonyl chloride were evaluated. The delivery of a test protein, lysozyme showed continuous release for 7 days. Immobilization of lysozyme caused by co-polymerization was 20% based on asymptotic recovery of released lysozyme. A theoretical shell thickness of 9.5 nm was estimated from a relative core volume of 80% and the average vesicle size.

TEMPO-mediated selective oxidation of substituted polysaccharides—an efficient approach for the determination of the degree of substitution at C-6

2,2,6,6-Tetramethyl-1-piperidinyloxy radical (TEMPO)-mediated oxidations of substituted polysaccharides were studied at pH 10.2 and at a temperature of 0 °C with NaOCl as the oxidant. The reaction is highly selective, and it was shown that the oxidation can proceed to a yield of nearly 100%. The oxidation process was investigated for several substituted polysaccharides, especially for a series of hydroxypropyl guar gums with different molar degrees of substitution. It was shown that this oxidation can be used for the determination of the degree of substitution at C-6 of the polysaccharide by comparing the difference in oxidation yield between substituted and natural polysaccharides. Studies on several hydroxypropyl guar gums showed that the degrees of substitution at C-6—for MS of 0.08, 0.34, 0.62, and 1.08—are 0.06, 0.24, 0.40, and 0.44, respectively. The results were extended to other polysaccharides such as carboxymethyl cellulose, cationic guar gum, carboxymethyl pullulan, and methyl cellulose. It can be concluded that the TEMPO-mediated oxidation is a useful method for the determination of the DS at the substituted C-6 position for different kinds of modified polysaccharides.

Synthesis and characterization of carboxymethyl chitosan containing functional ultraviolet absorber substituent

AbstractA series of carboxymethyl chitosan (CMC) with 2.4‐dihydoxybenzophenone (UV‐0) substituent were synthesized by the Mannich reaction of CMC hydrochloride and UV‐0 in the solvent of methanol and water. The different molar degree of substitution (MS) was achieved by changing the UV‐0 content. The effects of MS on ultraviolet absorbability, crystallinity, moisture‐absorption and ‐retention property, and photostability were investigated respectively. The obtained products were characterized by means of Fourier transform infrared spectra (FTIR), proton nuclear magnetic resonance spectroscopy (1H NMR), X‐ray diffraction, and UV spectrophotometer. It was found that the grafted products were water‐soluble, and the increased MS values could enhance the moisture‐retention property and photostability, while decreased the crystallinity and moisture‐absorption property. The ultraviolet absorption peaks became stronger by introducing UV‐0 into the CMC backbones. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007

Sulfobutyl Ether‐β‐Cyclodextrins: Promising Supramolecular Carriers for Aqueous Organometallic Catalysis

AbstractThe potentialities of sulfobutyl ether‐β‐CDs derivatives as supramolecular carrier in a biphasic Tsuji–Trost reaction catalyzed by a water‐soluble palladium complex of trisulfonated triphenylphosphine have been investigated. The efficiency of these cyclodextrins (CDs) strongly depends on the average molar substitution degree of cyclodextrin and the highest rate enhancements were obtained with cyclodextrins containing about 7 sulfobutyl ether groups. This result was attributed to the absence of a strong interaction between this cyclodextrin and the trisulfonated triphenylphosphine used to dissolve the catalyst in the aqueous phase and to the presence of an extended hydrophobic cavity allowing a better molecular recognition between the substrate and the cyclodextrin. This constitutes the first example of a non‐interacting β‐cyclodextrin/phosphine couple with high catalytic activities.

Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics?

The development of hydroxyethyl starches (HES) with low impact on blood coagulation but higher volume effect compared with the currently used HES solutions is of clinical interest. We hypothesized that high molecular weight, low-substituted HES might possess these properties. Thirty pigs were infused with three different HES solutions (20 ml kg(-1)) with the same degree of molar substitution (0.42) but different molecular weights (130, 500 and 900 kDa). Serial blood samples were taken over 24 h and blood coagulation was assessed by Thromboelastograph analysis and analysis of plasma coagulation. In addition, plasma concentration and in vivo molecular weight were determined and pharmacokinetic data were computed based on a two-compartment model. Thromboelastograph analysis and plasma coagulation tests did not reveal a more pronounced alteration of blood coagulation with HES 500 and HES 900 compared with HES 130. In contrast, HES 500 and HES 900 had a greater area under the plasma concentration-time curve [1542 (142) g min litre(-1), P<0.001, 1701 (321) g min litre(-1), P<0.001] than HES 130 [1156 (223) g min litre(-1)] and alpha half life (t(alpha)(1/2)) was longer for HES 500 [53.8 (8.6) min, P<0.01] and HES 900 [57.1 (12.3) min, P<0.01] than for HES 130 [39.9 (10.7) min]. Beta half life (t(beta)(1/2)), however, was similar for all three types of HES [from 332 (100) to 381 (63) min]. In low-substituted HES, molecular weight is not a key factor in compromising blood coagulation. The longer initial intravascular persistence of high molecular weight low-substituted HES might result in a longer lasting volume effect.

Studies on the Synthesis of 2,3‐O‐Hydroxyalkyl Ethers of Cellulose

Novel 2,3-O-hydroxyethyl- and 2,3-O-hydroxypropyl cellulose products were synthesized by heterogeneous etherification of 6-O-(4-monomethoxytrityl) cellulose (MMTC). Due to the very hydrophobic character of MMTC, the reaction was successful in the presence of anionic and non-ionic detergent in the reaction mixture yielding the 2,3-O-cellulose ethers with a molar degree of substitution (MS) varying between 0.25 and 2.00 after detritylation. The products were characterized by means of (1)H and (13)C NMR spectroscopy including two-dimensional methods. The 2,3-O-hydroxypropyl cellulose samples are soluble in water at a MS as low as 0.8. The spectroscopic studies showed that the unusual solubility results from a preferred substitution of hydroxy groups of the anhydroglucose unit while the newly formed hydroxy moieties are included in the reaction to a minor extent only. In contrast, conventionally synthesized hydroxypropyl cellulose is soluble in water starting at a MS of about 4.0 because of the formation of oxyethylene side chains. (13)C DEPT 135 NMR spectrum of 2,3-O-hydroxypropyl cellulose.

HPLC analysis of aliphatic and aromatic dicarboxylic acid cross-linkers hydrolyzed from carbohydrate polyesters for estimation of the molar degree of substitution

Quantitative analysis of carboxylic acids in hydrophilic matrixes remains a challenge despite the introduction of derivatization reagents for carboxylic acids nearly three decades ago. Analysis of many bifunctional ester forming polymer cross-linkers are additionally complicated by the their amphiphatic character. We report a sensitive and selective HPLC method to quantify organic dicarboxylic acids resulting from the hydrolytic degradation of cross-linked carbohydrate polyesters. An important group of cross-linkers encompassing C 7–C 10 aromatic and non-chromophoric aliphatic diacid chlorides were investigated. Specific validation is reported for terephthalic acid, diethylmalonic acid and sebacic acid. Linear calibration curves were obtained in the 0.5–15.0 μg/ml range corresponding to a mass fraction of 0.05–1.5% diacid to polyester. The accuracy and precision in this range was 94.4–114.1 and 6.1–24.8% RSD, respectively. This method is suitable for the routine determination of the molar or mass degree of substitution in carbohydrate polyesters.

The hydroxypropylation of starch in a self‐wiping twin screw extruder

AbstractPotato starch was chemically modified in an APV self‐wiping twin screw extruder to produce hydroxypropylated starch. The product obtained had a molar degree of substitution (MS) between 0.06 and 0.26. The selectivity of the hydroxypropylation reaction varied between 50 and 95%, yields varied between 15 and 95%, and conversions between 30 and 91%. Using viscosity data of native and hydroxypropylated starch, together with extruder parameters like temperatures, residence time distribution, and shear rates, a model was set up to predict the MS values, conversions, and selectivities. With this model, interactions between temperature, reaction, and viscosity can be understood and predicted. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 56–68, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10034

Determination of the Molar Mass and the Radius of Gyration, Together with their Distributions for Methylhydroxyethylcelluloses

Three molar mass series were produced by different methods of degradation (namely ultrasonic (seven samples), oxidation (seven samples) and autoclaving (eight samples)) from a methylhydroxyethylcellulose (MHEC) sample with an average degree of substitution (DS) of 1.3, a molar degree of substitution (MS) of 0.46, a radius of gyration of 67 nm and a weight-average molar mass, Mw, of 318,000 g/mol. The degraded samples were characterized in terms of their molar mass and particle size together with their respective distributions with a hyphenated apparatus consisting of size exclusion chromatography and multi-angle laser light scattering and concentration detector (SEC/MALLS/DRI) at 25 °C in 0.1 M NaNO3 solution (with 200 ppm NaN3 as antibactericide). The refractive index increment was determined as dn/dc = 0.135 cm3/g. It was possible to reduce the weight-average molar mass down to approximately 10% of the initial molar mass using all the methods. In a comparison of the three degradation methods it was shown that only ultrasonic degradation retains the monomodal distribution, whereas the other two degradation methods yield a bimodal molar mass distribution. Consequently, only ultrasonic degradation represents a suitable method for producing homologous molar mass series. An RG–M relationship of RG = 0.0511 × M0.56 was established for the sample used in this case, and from this it was possible to calculate an [η]–M relationship of [η] = 0.3587 × M0.68.

Effect of Reaction Conditions and Alkyl Chain Lengths on the Properties of Hydroxyalkyl Starch Ethers

Starch applications in the plastics industry have been investigated intensively for many years. Unfortunately, native starch is unsuitable for most applications in polymers, because of its hydrophilic and brittle character. Modification of native starch can be a solution of this problem. In our research programme we developed an environmentally friendly process for the preparation of starch derivatives with long hydrophobic side chains based on natural products derived from vegetable fats and oils on the one hand and amylomaize starch on the other hand. In this process modification is carried out by the addition of longchain 1,2-epoxyalkanes (chain lengths varying between 6—18 C atoms) to starch in an alkaline aqueous medium. Reaction yields and molar degrees of substitution depended on chain length, reaction time, temperature and catalyst concentration. Under optimised reaction conditions molar degrees of substitution of hydroxyalkyl starch ethers for theoretical molar substitution (MS) = 3.0 decreased from MS=1.8 (C6 starch ether) to MS=0.2 (C18 starch ether), respectively. Hydrophobic properties of starch products were measured in order to reveal structural effects obtained at different reaction conditions. Water solubility and water absorption properties of hydroxyalkyl starch ethers decreased with increasing chain length and number of hydroxyalkyl substituents. Thermal and thermoplastic properties of starch ethers were investigated in order to determine their potential use as biodegradable polymers in the plastics industry. As expected, thermoplasticity of starch ethers increased with increasing MS and increasing chain length of the hydroxyalkyl side groups.