Synthesis of carboxyl cellulose sulfates with regioselective sulfation and regiospecific oxidation using cellulose trifluoroacetate as intermediates

Synthesis of cellulose sulfates (CSs) and carboxyl cellulose sulfates (COCSs) with regioselectively or regiospecifically distributed functional groups within anhydroglucose units was reported. CS with regioselectively distributed sulfate groups at 2,3-O- or 2,6-O-position were homogeneously synthesized and cellulose trifluoroacetate (CTFA) was used as intermediates. The trifluoroacetyl groups were detected primarily at 6-O-position and their distributions could be altered by changing the amount of trifluoroacetyl anhydride (TFAA). Various sulfating agents were used for further homogeneous sulfation of CTFA. The total degree of sulfation (DS_S) and the distribution of sulfate groups within the repeating units were affected by the amount of TFAA, the type and amount of sulfating agents. Subsequent homogenous 4-acetamide-TEMPO or TEMPO-mediated oxidation of CS led to COCS with carboxyl groups regiospecifically distributed at C6 position, which may be interesting structural mimics for natural occurring heparin.     

Molecular weight-dependent anticoagulation activity of sulfated cellulose derivatives

This work is to examine the molecular weight (MW)-anticoagulation activity relationship of sulfated cellulose derivatives (cellulose sulfates, CS). The initial CS with a degree of substitution (1.59) was prepared by homogeneous sulfation of microcrystalline cellulose in an ionic liquid [C₄mim]Cl. It was then hydrolyzed in a dilute acidic solution and separated into four MW fractions of 59, 23, 10 × 10³ g/mol and below 2.7 × 10³ g/mol. The anticoagulation activities based on in vitro assays of coagulation time and coagulation factors in human plasma showed a positive correlation with the MW of CS, while the activity assay of clotting time in rats exhibited a negative correlation with the MW 10–59 × 10³ g/mol, and the fraction with a MW <2.7 × 10³ g/mol exhibited a more moderate and durable activity. The results indicate that MW is a major factor on the anticoagulant properties of CS derivatives and higher MW range is favorable for in vitro, and lower MW suitable for in vivo applications.     

Comparison between various Keggin and Wells–Dawson sandwich‐type polyoxometalates in catalytic oxidation of cyclooctene and cyclohexene with hydrogen peroxide

The catalytic performance of tetra‐n‐butylammonium salts of Keggin and Wells–Dawson sandwich‐type polyoxotungstates, [M₄(PW₉O₃₄)₂]^m? and [M₄(P₂W₁₅O₅₆)₂]^n? (M = Mn²⁺, Fe³⁺, Co²⁺, Ni²⁺, Zn²⁺), in the oxidation of cyclooctene and cyclohexene with 30% hydrogen peroxide under various conditions was investigated. In comparison, Wells–Dawson sandwich‐type polyoxometalates were found to be less active than Keggin ones. In both of them, those containing Zn and Fe gave higher conversions for different oxidation conditions. These catalysts showed very good reusability in the oxidation reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Entanglement properties of cellulose and amylose in an ionic liquid

Concentrated solutions of cellulose and amylose were prepared with an ionic liquid 1‐butyl‐3‐methylimidazolium chloride (BmimCl), which was chosen as a good solvent for these polysaccharides. Dynamic viscoelasticity of the concentrated solutions was examined to obtain the molecular weight between entanglements, M_e. The value of M_e in the molten state (M_e,melt), a material constant that reflecting the entanglement properties, was determined for cellulose and amylose by extrapolating M_e to the “melt.” A marked difference in M_e,melt was found: 3.2 × 10³ for cellulose and 2.5 × 10⁴ for amylose. The value of M_e,melt for cellulose, which is composed of β‐(1,4) bonding of D ‐glucose units, is very close to those for polysaccharides with a random‐coil conformation such as agarose and gellan in BmimCl. The much larger M_e,melt for amylose can be attributed to the helical nature of the amylose chain, α‐(1,4)‐linked D ‐glucose units. The effect of concentration on the zero‐shear viscosity for the solutions of cellulose and amylose was also examined. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

FT Raman investigation of sodium cellulose sulfate

FT Raman investigation of sodium cellulose sulfates (NaCS) was reported. Different NaCS were prepared by two diverse sulfation methods and their total degrees of substitution (DS) of sulfate groups were determined through either ¹³C-NMR spectroscopy or elemental analysis. Subsequently, these NaCS were characterized with FT Raman spectroscopy. The caused bands through the introduction of the sulfate groups in cellulose chain were explained and assigned. Additionally, a strong linear correlation between the areas under the bands ascribed to the stretching vibrations of C–O–S groups and the total DS of NaCS was presented. A rapid method of quantifying the total DS of NaCS was established. Finally, sodium sulfate (Na₂SO₄), a salt that is very often produced during the sulfation of cellulose, was found to be analyzable even with a weight content of 0.12% in NaCS. The method of quantifying the content of this salt in NaCS was investigated with Raman spectroscopy.     

Electron transfer at an encapsulated cobalt(III) centre: kinetics of oxidation of thiourea and 1,1,3,3-tetramethyl-2-thiourea in aqueous acidic media

Summary The stoichiometries, kinetics and mechanisms of oxidation of (NH₂)₂CS (1) and (Me₂N)₂CS (2) to the corresponding disulphides by Co^IIIM (M = W₁₂O₄₀ ^∞-) in aqueous HC1O₄ were investigated. The reaction with (1) follows the empirical rate law- d[oxidant] = k[reductant][oxidant] where k = 12.5 ± 0.3 m⁻¹ s⁻¹ at 25° C, while that with (2) follows the equation- d[oxidant] = a + b [reductant] [reductant] [oxidant] where a = 5.4 × 10⁴ M⁻¹s⁻¹ and b = 3.3 × 10⁶M⁻² s⁻¹ at 25° C. Free radicals are important in the reactions and possible reaction mechanisms are suggested and discussed.     

Dilute solution properties of cellulose in LiOH/urea aqueous system

Cellulose was dissolved rapidly in 4.6 wt % LiOH/15 wt % urea aqueous solution and precooled to –10 °C to create a colorless transparent solution. ¹³C‐NMR spectrum proved that it is a direct solvent for cellulose rather than a derivative aqueous solution system. The result from transmission electron microscope showed a good dispersion of the cellulose molecules in the dilute solution at molecular level. Weight‐average molecular weight (M_w), root mean square radius of gyration (〈s²〉_z^1/2), and intrinsic viscosity ([η]) of cellulose in LiOH/urea aqueous solution were examined with laser light scattering and viscometry. The Mark–Houwink equation for cellulose in 4.6 wt % LiOH/15 wt % urea aqueous solution was established to be [η] = 3.72 × 10^?2 M in the M_w region from 2.7 × 10⁴ to 4.12 × 10⁵. The persistence length (q), molar mass per unit contour length (M_L), and characteristic ratio (C_∞) of cellulose in the dilute solution were given as 6.1 nm, 358 nm^?1, and 20.8, respectively. The experimental data of the molecular parameters of cellulose agreed with the Yamakawa–Fujii theory of the worm‐like chain, indicating that the LiOH/urea aqueous solution was a desirable solvent system of cellulose. The results revealed that the cellulose exists as semistiff‐chains in the LiOH/urea aqueous solution. The cellulose solution was stable during measurement and storage stage. This work provided a new colorless, easy‐to‐prepare, and nontoxic solvent system that can be used with facilities to investigate the chain conformation and molecular weight of cellulose. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3093–3101, 2006     

Synthesis of polymethacrylate derivatives having sulfated maltoheptaose side chains with anti‐HIV activities

Anti‐HIV (human immunodeficiency virus) active polymethacrylates having pendant sulfated oligosaccharides were synthesized, and the relationship between structures and biological activities of the polymethacrylates was examined. Acetylated 1‐O‐methacryloyl maltoheptaoside (MA‐AcM7) was polymerized with AIBN as an initiator to give polymethacrylates having a pendant acetylated maltoheptaose in every repeating unit, poly(MA‐AcM7)s. After hydroxyl groups were recovered by deacetylation, the polymethacrylates having maltoheptaose units, poly(MA‐M7)s, were sulfated to give polymethacrylates having sulfated maltoheptaose side‐chains, poly(MA‐SM7)s, with degrees of sulfation of 1.1 to 2.7 (maximum, 3.0). These polymethacrylates including sulfated oligosaccharides exhibited low anti‐HIV activities represented by the 50% protecting concentration (EC₅₀) in the range of 15–62 μg/mL and low blood anticoagulant activities around 10 unit/mg (standard dextran sulfate, 22.7 unit/mg). The anti‐HIV activity increased with increasing degree of sulfation to reach EC₅₀ of 15–16 μg/mL. In addition, copolymerization of MA‐AcM7 with methyl methacrylate (MMA) and subsequent sulfation gave polymethacrylates consisting of various proportions of highly sulfated maltoheptaose and MMA units. It was revealed that the anti‐HIV activity increased with decreasing proportion of the sulfated oligosaccharide moiety and that a copolymethacrylate having 22 mol % of sulfated maltoheptaose units (DS = 3.0) had a high anti‐HIV activity in the EC₅₀ of 0.3 μg/mL. The blood anticoagulant activity increased slightly from 9 to 18 unit/mg with decreasing proportion of the sulfated maltoheptaose units. These results suggested that the biological activities were influenced strongly by the spatial distance between sulfated oligosaccharide substituents in the polymethacrylate main chain. Distinction and conformation of the oligosaccharide side chains also played an important role. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 789–800, 1999     

Behavior of cellulose in NaOH/Urea aqueous solution characterized by light scattering and viscometry

Cellulose was dissolved in 6 wt % NaOH/4 wt % urea aqueous solution, which was proven by a ¹³C NMR spectrum to be a direct solvent of cellulose rather than a derivative aqueous solution system. Dilute solution behavior of cellulose in a NaOH/urea aqueous solution system was examined by laser light scattering and viscometry. The Mark–Houwink equation for cellulose in 6 wt % NaOH/4 wt % urea aqueous solution at 25 °C was [η] = 2.45 × 10^?2 weight‐average molecular weight (M_w)^0.815 (mL g^?1) in the M_w region from 3.2 × 10⁴ to 12.9 × 10⁴. The persistence length (q), molar mass per unit contour length (M_L), and characteristic ratio (C_∞) of cellulose in the dilute solution were 6.0 nm, 350 nm^?1, and 20.9, respectively, which agreed with the Yamakawa–Fujii theory of the wormlike chain. The results indicated that the cellulose molecules exist as semiflexible chains in the aqueous solution and were more extended than in cadoxen. This work provided a novel, simple, and nonpollution solvent system that can be used to investigate the dilute solution properties and molecular weight of cellulose. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 347–353, 2004     

Synthesis of a Targeted Library of Heparan Sulfate Hexa‐ to Dodecasaccharides as Inhibitors of β‐Secretase: Potential Therapeutics for Alzheimer’s Disease

Heparan sulfates (HS) are a class of sulfated polysaccharides that function as dynamic biological regulators of the functions of diverse proteins. The structural basis of these interactions, however, remains elusive, and chemical synthesis of defined structures represents a challenging but powerful approach for unravelling the structure–activity relationships of their complex sulfation patterns. HS has been shown to function as an inhibitor of the β‐site cleaving enzyme β‐secretase (BACE1), a protease responsible for generating the toxic Aβ peptides that accumulate in Alzheimer’s disease (AD), with 6‐O‐sulfation identified as a key requirement. Here, we demonstrate a novel generic synthetic approach to HS oligosaccharides applied to production of a library of 16 hexa‐ to dodecasaccharides targeted at BACE1 inhibition. Screening of this library provided new insights into structure–activity relationships for optimal BACE1 inhibition, and yielded a number of potent non‐anticoagulant BACE1 inhibitors with potential for development as leads for treatment of AD through lowering of Aβ peptide levels.     

Simultaneous Al2O3 Doping and Sulfation in Hierarchically Porous ZrO2 Solid Acids by an One‐pot Synthesis for Enhanced Recycling Catalytic Performances

Alumina doping and sulfation in hierarchically porous zirconia solid acids have been achieved simultaneously via one‐pot and bi‐surfactant‐assisted self‐assembly process, using aluminum sulfate as both Al and SO₄^2? sources. The prepared composite solid acids showed much enhanced acidity and recycling catalytic activity for an esterification reaction compared with sulfated zirconia without alumina doping and Al‐doped sulfated zirconia without hierarchically porous structure.     

Cellulose derivatives from cellulosic material isolated from Agave lechuguilla and fourcroydes

Fibers isolated from Agave lechuguilla(lechuguilla) and fourcroydes (henequen) contain about 80%cellulose, 5% hemicellulose and 15% lignin. They are a renewable resource,interesting as feedstock for new products obtained by chemicalfunctionalization. In the present paper the reactivity of such fibrousmaterialsunder typical conditions for modification of cellulose was studied. Treatmentwith n-octanol/aqueous NaOH of the fibers leads to an activated expandedgel-like material with enhanced accessibility. Carboxymethylation, sulfation,acetylation and tritylation reactions as well as subsequent carboxymethylationof the trityl derivative and selective oxidation of the primary hydroxylfunction of carboxymethylated products with TEMPO/NaBr/NaClO were successfullycarried out under conditions typical for cellulose reactions. The products werecharacterized by means of ¹³C-NMR and ¹H-NMR spectroscopyandHPLC after complete depolymerization, by GPC, and by the determination ofsolubility.     

NMR Investigation of the Influence of Sulfate Groups at C‐2 and C‐4 on the Conformational Behavior of Fucoidan Fragments with Homo‐(1→3)‐Linked Backbone#

The conformational behavior of 2‐O‐ and 4‐O‐sulfated derivatives of linear (1→3)‐linked di‐, tri‐, and tetrafucosides and 2,3‐branched tetrafucoside was studied by means of theoretical molecular modeling and experimental determination of trans‐glycosidic vicinal coupling constants ³J_C,H. It was shown that O‐sulfation of (1→3)‐linked oligofucosides restricts their conformational flexibility and changes the conformational equilibrium if compared with the parent nonsulfated oligosaccharides. In the case of 2‐O‐sulfated oligofucosides, the conformations of O‐glycoside linkages depend on its location within the oligosaccharide chain and the chain length as well as on the presence of a 2,3‐branch, whereas the conformation of the (1→3)‐linkage in the presence of a 4‐O‐sulfate group only depends on the presence of a 2,3‐branch.     

Sulfation of Hydroxyethyl Cellulose by N(SO3Na)3 and the Anticoagulant Activity of Sulfated Hydroxyethyl Cellulose

Hydroxyethyl cellulose sulfate (HECS) was synthesized by sulfation of hydroxyethyl cellulose with N(SO₃Na)₃, which was manufactured by reaction of sodium bisulfite and sodium nitrite. Barium sulfate nephelometry and light scattering method were used to determine degrees of substitution (DSs) and molecular weights (M_ws), respectively. Sulfate products with DS values from 0.26 to 1.88 and M_w in the range of 12.1–54.8 kDa were obtained at temperatures from 30°C to 80°C. Furthermore, the anticoagulant activity of HECS with different DSs, concentrations, and M_ws was studied. Clotting assays revealed that the introduction of sulfate groups into hydroxyethyl cellulose could improve its anticoagulant activity.     

[3+2] Cycloadditions of Metallo Nitrile Ylides and Metallo Nitrile Imines with Metal Carbonyl,Thiocarbonyl, and Isocyanide Complexes: Heterodimetallic Systems with Bridging Heterocycles [1]

The reactions of [Re(CO)₆]⁺, [FeCp(CO)₂CS]⁺ and [FeCp(CNPh)₃]⁺ with the metallo nitrile ylides [M^–{C⁺=N–C^–(H)CO₂Et}(CO)₅]^– (M = Cr, W) and the chromio nitrile imine [Cr^–{C⁺=N–N^–H}(CO)₅]^– (generated by mono‐α‐deprotonation of the parent isocyanide complexes) to give neutral 5‐metallated 1,3‐oxazolin‐ ( 1 ), 1,3‐thiazolin‐ ( 2 ), imidazolin‐ ( 3 , 4 ), 1,3,4‐oxdiazolin‐ ( 5 ), 1,3,4‐thiadiazolin‐ ( 6 ) and 1,3,4‐triazolin‐2‐ylidene ( 8 ) chromium and tungsten complexes represent the first all‐organometallic versions of Huisgen’s 1,3‐dipolar cycloadditions. The formation of 6 and 8 is accompanied by partial decomposition to (OC)₅Cr–C≡N–FeCpL₂ {L = CO ( 7 ), CNPh ( 9 )}. The structures of 4a and 5 have been characterized by X‐ray diffraction.     

Dicarboxylic acid promoted immortal copolymerization for controllable synthesis of low‐molecular weight oligo(carbonate‐ether) diols with tunable carbonate unit content

Low‐molecular weight oligo(carbonate‐ether) diols are important raw materials for polyurethane formation, which with tunable carbonate unit content (CU) may endow new thermal and mechanical performances to polyurethane. Herein, facile synthesis of oligo(carbonate‐ether) diols with number average molecular weight (M_n) below 2000 g mol^?1 and CU tunable between 40% and 75% are realized in high activity by immortal copolymerization of CO₂/propylene oxide (PO) using zinc‐cobalt double metal cyanide complex (Zn‐Co‐DMCC) in the presence of sebacic acid (SA). M_n of the oligomer is in good linear relationship to the mole ratio of PO and SA (PO/SA) and hence can be precisely controlled by adjusting PO/SA. Besides, the molecular weight distribution is quite narrow due to the rapid reversible chain transfer in the immortal copolymerization. High pressure and low temperature are favorable for raising CU. In all the reactions, the weight fraction of propylene carbonate (W_PC) can even be controlled as low as 2.0 wt %, and the catalytic activity of Zn‐Co‐DMCC is above 1.0 kgg^?1 cat. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Phenomenology of oxidation of a cumene feed containing hydroperoxide: I. Two paths of cumene hydroperoxide formation reaction

This article presents direct evidence of the occurrence of cumene oxidation resulting from the presence of gaseous oxygen (O₂^gas) at the gas-liquid interface, demonstrating a markedly higher magnitude of process selectivity, as compared to oxidation that is promoted by dissolved oxygen (₂^liquid). The significant contribution of O₂^gas to the formation of cumene hydroperoxide under bubble-type process conditions is also discussed, emphasizing that the hydroperoxide formation rate is composed of two components: W _total = W ₁^gas + W ₁^liquid, where the first component, W ₁^gas, is a function of k ₁^gas, [O₂^gas], and of the liquid-gas interface area, while the second component, W ₁^liquid, is subject to equation: W = k[R·][O₂^liquid].     

Characterization of Xylansulfate by Size Exclusion Chromatography

Abstract

A sulfated, low molecular weight beech xylan was fractionated preparatively on Sephadex G-50 into ten fractions with molecular weights from 17 000 to 1 800. The degree of sulfation, refractive index increment, molecular weight, and specific optical rotation of each fraction was determined. The fractions were then used to calibrate a Sephacryl S–200 gel column for the molecular weight distribution analysis of xylansulfate.

The molecular weights, M _W, obtained by SEC for samples of xylansulfate were in good agreement (within 4 ± 1%) to the values derived by low angle light scattering.     

Fine Control of the Redox Reactivity of a Nonheme Iron(III)–Peroxo Complex by Binding Redox‐Inactive Metal Ions

Redox‐inactive metal ions are one of the most important co‐factors involved in dioxygen activation and formation reactions by metalloenzymes. In this study, we have shown that the logarithm of the rate constants of electron‐transfer and C−H bond activation reactions by nonheme iron(III)–peroxo complexes binding redox‐inactive metal ions, [(TMC)Fe^III(O₂)]⁺‐M^{n +} (M^{n +}=Sc³⁺, Y³⁺, Lu³⁺, and La³⁺), increases linearly with the increase of the Lewis acidity of the redox‐inactive metal ions (ΔE ), which is determined from the g_zz values of EPR spectra of O₂^.−‐M^{n +} complexes. In contrast, the logarithm of the rate constants of the [(TMC)Fe^III(O₂)]⁺‐M^{n +} complexes in nucleophilic reactions with aldehydes decreases linearly as the ΔE value increases. Thus, the Lewis acidity of the redox‐inactive metal ions bound to the mononuclear nonheme iron(III)–peroxo complex modulates the reactivity of the [(TMC)Fe^III(O₂)]⁺‐M^{n +} complexes in electron‐transfer, electrophilic, and nucleophilic reactions.     

Regioselective sulfation of trimethylsilyl cellulose using different SO3-complexes

Trimethylsilyl cellulose (DS_Si = 2.9) dissolved in dry tetrahydrofurane was reacted with SO₃-complexes of N,N-dimethylformamide, triethylamine, pyridine and ethyldiisopropylamine. Under the given reaction conditions, i.e. 25 °C, 24 h, 2.2 mol equivalent SO₃-complex, the SO₃ attacks the trimethylsilyl ether groups followed by the formation of sodium sulfate cellulose under sodium hydroxide work-up conditions. The regioselectivity of the sulfation is controlled by the complex partner of SO₃. Cellulose sulfates with preferred O-6 sulfation were obtained using SO₃-N,N-dimethylformamide. In case of SO₃-triethylamine, cellulose-2-sulfates could be prepared with good regioselectivity. Small residual amounts of silicon in the cellulose sulfates (0.1–0.2% w/w) can be quantified using inductively coupled plasma-optical emission spectroscopy (ICP-OES), and can be decreased up to 80% by heating (70 °C, 24 h) the polymers in vacuum.