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In this study, polysaccharides were extracted at a rate of 87.5% ± 1.5% from native dandelion roots, and the dandelion root polysaccharides (DRPs) were then chemically modified to obtain sulfated polysaccharides (SDRPs) with a degree of substitution of 1.49 ± 0.07. The effects of modification conditions, physicochemical characterizations, structural characteristics, antioxidant properties, hypoglycemic activity, and proliferative effects on probiotics of DRP derivatives were further investigated. Results showed that the optimum conditions for sulfation of DRPs included esterification reagents (concentrated sulfuric acid: n-butanol) ratio of 3:1, a reaction temperature of 0 °C, a reaction time of 1.5 h, and the involvement of 0.154 g of ammonium sulfate. The DRPs and SDRPs were composed of six monosaccharides, including mannose, glucosamine, rhamnose, glucose, galactose, and arabinose. Based on infrared spectra, the peaks of the characteristic absorption bands of S=O and C-O-S appeared at 1263 cm−1 and 836 cm−1. Compared with DRPs, SDRPs had a significantly lower relative molecular mass and a three-stranded helical structure. NMR analysis showed that sulfated modification mainly occurred on the hydroxyl group at C6. SDRPs underwent a chemical shift to higher field strength, with their characteristic signal peaking in the region of 1.00–1.62 ppm. Scanning electron microscopy (SEM) analysis indicated that the surface morphology of SDRPs was significantly changed. The structure of SDRPs was finer and more fragmented than DRPs. Compared with DRPs, SDRPs showed better free radical scavenging ability, higher Fe2+chelating ability, and stronger inhibition of α-glucosidase and α-amylase. In addition, SDRPs had an excellent promotional effect on the growth of Lactobacillus plantarum 10665 and Lactobacillus acidophilus. Therefore, this study could provide a theoretical basis for the development and utilization of DRPs.

Mathematical modeling of columnar leaching is a useful tool for predicting and evaluating the kinetics of copper extraction. One commonly used model for this process is the shrinking core model (SCM). In this study, the aim was to develop a model for column leaching of oxidized copper ore based on the SCM, which incorporates the ore sulfation stage before leaching. In sulfation and leaching laboratory-scale tests, we studied the effect of acid dosage (at 22.8, 34.2, and 45.6 kg/t), humidity (at 90%, 100%, and 110% of the saturation humidity of the mineral), ore granulometry (−3/4″ and −3/8″), and rest time (at 24, 48, 72, and 96 h) on sulfation. We found that the highest sulfation reached 49.7% for both granulometries in studies. In the column tests, the effects of acid dosage (at 34.2, 45.6 kg/t), ore granulometry (−3/4″, −3/8″), and rest time (at 24, 48 h) were studied. When the SCM was applied to these tests, we obtained fit qualities within 63.4% and 74.9%. By incorporating the sulfation factor into the SCM predictions, we observed an average increase in adjustment between 24% and 28%. This method is effective for minerals and operating conditions different from the ones studied.

The Beckmann rearrangement of ketoximes to their corresponding amides, using a Brønsted acid-mediated fragmentation and migration sequence, has found wide-spread industrial application. We postulated that the development of a methodology to access ylideneamino sulfates using tributylsulfoammonium betaine (TBSAB) would afford isolable Beckmann-type intermediates and competent partners for subsequent rearrangement cascades. The ylideneamino sulfates generated, isolated as their tributylammonium salts, are sufficiently activated to undergo Beckmann rearrangement without additional reagent activation. The generation of sulfuric acid in situ from the ylideneamino sulfate giving rise to a routine Beckmann rearrangement and additional amide bond cleavage to the corresponding aniline was detrimental to reaction success. The screening of bases revealed inexpensive sodium bicarbonate to be an effective additive to prevent classic Brønsted acid-mediated fragmentation and achieve optimal conversions of up to 99%.

The C(sp2)-aryl sulfonate functional group is found in bioactive molecules, but their synthesis can involve extreme temperatures (>190 °C or flash vacuum pyrolysis) and strongly acidic reaction conditions. Inspired by the 1917 Tyrer industrial process for a sulfa dye that involved an aniline N(sp2)-SO3 intermediate en route to a C(sp2)-SO3 rearranged product, we investigated tributylsulfoammonium betaine (TBSAB) as a milder N-sulfamation to C-sulfonate relay reagent. Initial investigations of a stepwise route involving TBSAB on selected anilines at room temperature enabled the isolation of N(sp2)-sulfamate. Subsequent thermal rearrangement demonstrated the intermediary of a sulfamate en route to the sulfonate; however, it was low-yielding. Investigation of the N-sulfamate to C--sulfonate mechanism through control experiments with variation at the heteroatom positions and kinetic isotope experiments (KIEH/D) confirmed the formation of a key N(sp2)-SO3 intermediate and further confirmed an intermolecular mechanism. Furthermore, compounds without an accessible nitrogen (or oxygen) lone pair did not undergo sulfamation- (or sulfation) -to-sulfonation under these conditions. A one-pot sulfamation and thermal sulfonation reaction was ultimately developed and explored on a range of aniline and heterocyclic scaffolds with high conversions, including N(sp2)-sulfamates (O(sp2)-sulfates) and C(sp2)-sulfonates, in up to 99 and 80% (and 88% for a phenolic example) isolated yield, respectively. Encouragingly, the ability to modulate the ortho-para selectivity of the products obtained was observed under thermal control. A sulfonated analog of the intravenous anesthetic propofol was isolated (88% yield), demonstrating a proof-of-concept modification of a licensed drug alongside a range of nitrogen- and sulfur-containing heterocyclic fragments used in drug discovery.

Seaweed polysaccharides can act as substitutes for synthetic compounds present in commercial stimulants and fertilizers used in agriculture to improve crop yields and vigor. In this study, three different polysaccharides (alginate, agar, and carrageenan) were extracted from one brown seaweed, Saccorhiza polyschides, and two red seaweeds, Gracilaria gracilis and Chondrus crispus, respectively, and applied to potted turnip greens (Brassica napus L.), with the intention to analyze their impact on plant growth, development, and metabolism. Turnip greens treated with polysaccharides, especially carrageenan of C. crispus, showed the best results in improving the crop productivity in terms of plant length and weight, number of leaves, nutrient and pigment content, and soil fertility compared with turnip greens from the negative control or those treated with a commercial leaf fertilizer. λ-carrageenan extracted from the tetrasporophyte generation of C. crispus had the highest bioactivity and positive effect on turnip greens among all treatments. λ-carrageenan has been shown to improve plant growth; increase the plant’s biomass (plant leaves: CC(T) (40.80 ± 5.11 g) compared to the positive control (15.91 ± 15.15 g)) and root system; enhance photosynthetic activity; increase the uptake of soil nutrients; and protect plants against abiotic and biotic stresses, stimulating the production of secondary metabolites and managing its defense pathways. Seaweed-extracted polysaccharides have the potential to be used in sustainable agriculture.

This study aimed to test the preventive anti-inflammatory properties of Chinese yam polysaccharides (CYP) and sulfated Chinese yam polysaccharides (SCYP) on LPS-induced systemic acute inflammation in mice and investigate their mechanisms of action. The results showed that SCYP can efficiently reduce plasma TNF-α and IL-6 levels, exhibiting an obvious anti-inflammation ability. Moreover, SCYP reduced hepatic TNF-α, IL-6, and IL-1β secretion more effectively than CYP, and significantly altered intestinal oxidative stress levels. In addition, a 16S rRNA gene sequencing analysis showed that CYP regulated the gut microbiota by decreasing Desulfovibrio and Sutterella and increasing Prevotella. SCYP changed the gut microbiota by decreasing Desulfovibrio and increasing Coprococcus, which reversed the microbiota dysbiosis caused by LPS. Linear discriminant analysis (LDA) effect size (LEfSe) revealed that treatment with CYP and SCYP can produce more biomarkers of the gut microbiome that can promote the proliferation of polysaccharide-degrading bacteria and facilitate the intestinal de-utilization of polysaccharides. These results suggest that SCYP can differentially regulate intestinal flora, and that they exhibit anti-inflammatory effects, thus providing a new reference to rationalize the exploitation of sulfated yam polysaccharides.

Magnolol, the main active ingredient of Magnolia officinalis, has been reported to display anti-inflammatory activity. Sulfation plays an important role in the metabolism of magnolol. The magnolol sulfated metabolite was identified by the ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and a proton nuclear magnetic resonance (1H-NMR). The magnolol sulfation activity of seven major recombinant sulfotransferases (SULTs) isoforms (SULT1A1*1, SULT1A1*2, SULT1A2, SULT1A3, SULT1B1, SULT1E1, and SULT2A1) was analyzed. The metabolic profile of magnolol was investigated in liver S9 fractions from human (HLS9), rat (RLS9), and mouse (MLS9). The anti-inflammatory effects of magnolol and its sulfated metabolite were evaluated in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Magnolol was metabolized into a mono-sulfated metabolite by SULTs. Of the seven recombinant SULT isoforms examined, SULT1B1 exhibited the highest magnolol sulfation activity. In liver S9 fractions from different species, the CLint value of magnolol sulfation in HLS9 (0.96 µL/min/mg) was similar to that in RLS9 (0.99 µL/min/mg) but significantly higher than that in MLS9 (0.30 µL/min/mg). Magnolol and its sulfated metabolite both significantly downregulated the production of inflammatory mediators (IL-1β, IL-6 and TNF-α) stimulated by LPS (p < 0.001). These results indicated that SULT1B1 was the major enzyme responsible for the sulfation of magnolol and that the magnolol sulfated metabolite exhibited potential anti-inflammatory effects.

White adipose tissues are major endocrine organs that release factors, termed adipokines, which affect other major organ systems. The development and functions of adipose tissues depend largely upon the glycosaminoglycan heparan sulfate. Heparan sulfate proteoglycans (HSPGs) surround both adipocytes and vascular structures and facilitate the communication between these two components. This communication mediates the continued export of adipokines from adipose tissues. Heparan sulfates regulate cellular physiology and communication through a sulfation code that ionically interacts with heparan-binding regions on a select set of proteins. Many of these proteins are growth factors and chemokines that regulate tissue function and inflammation. Cells regulate heparan sulfate sulfation through the release of heparanases and sulfatases. It is now possible to tissue engineer vascularized adipose tissues that express heparan sulfate proteoglycans. This makes it possible to use these tissue constructs to study the role of heparan sulfates in the regulation of adipokine production and release. It is possible to regulate the production of heparanases and sulfatases in order to fine-tune experimental studies.

As renewable energy sources, such as solar systems, are becoming more popular, the focus is moving into more effective utilization of these energy sources and harvesting more energy for intermittency reduction in this renewable source. This is opening up a market for methods of energy storage and increasing interest in batteries, as they are, as it stands, the foremost energy storage device available to suit a wide range of requirements. This interest has brought to light the downfalls of batteries and resultantly made room for the investigation of ultra-capacitors as a solution to these downfalls. One of these downfalls is related to the decrease in capacity, and temperamentality thereof, of a battery when not used precisely as stated by the supplier. The usable capacity is reliant on the complete discharge/charge cycles the battery can undergo before a 20% degradation in its specified capacity is observed. This article aims to investigate what causes this degradation, what aggravates it and how the degradation affects the usage of the battery. This investigation will lead to the identification of a gap in which this degradation can be decreased, prolonging the usage and increasing the feasibility of the energy storage devices.

A simple, sensitive, and reliable quantification and identification method was developed and validated for simultaneous analysis of 58 bile acids (BAs) in human and rodent (mouse and rat) fecal samples. The method involves an extraction step with a 5% ammonium–ethanol aqueous solution; the BAs were quantified by high-resolution mass spectrometry (ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, UPLC–Q-TOF). The recoveries were 80.05–120.83%, with coefficient variations (CVs) of 0.01–9.82% for three biological species. The limits of detection (LODs) were in the range of 0.01–0.24 μg/kg, and the limits of quantification (LOQs) ranged from 0.03 to 0.81 μg/kg. In addition, the analytical method was used to identify and quantify BAs in end-stage renal disease (ESRD) patients, C57BL/6 mice, and Sprague-Dawley (SD) rats. The fecal BA profile and analysis of BA indices in these samples provide valuable information for further BA metabolic disorder research.

Urolithiasis is a common urological disease characterized by the presence of a stone anywhere along the urinary tract. The major component of such stones is calcium oxalate, and reactive oxygen species act as an essential mediator of calcium oxalate crystallization. Previous studies have demonstrated the antioxidant and antiurolithiatic activities of sulfated polysaccharides. In this study, native sulfated galactans (N-SGs) with a molecular weight of 217.4 kDa from Gracilaria fisheri were modified to obtain lower molecular weight SG (L-SG) and also subjected to sulfation SG (S-SG). The in vitro antioxidant and antiurolithiatic activities of the modified substances and their ability to protect against sodium oxalate-induced renal tubular (HK-2) cell death were investigated. The results revealed that S-SG showed more pronounced antioxidant activities (DPPH and O2− scavenging activities) than those of other compounds. S-SG exhibited the highest antiurolithiatic activity in terms of nucleation and aggregation, as well as crystal morphology and size. Moreover, S-SG showed improved cell survival and increased anti-apoptotic BCL-2 protein in HK-2 cells treated with sodium oxalate. Our findings highlight the potential application of S-SG in the functional food and pharmaceutical industries.

Xanthan is an important polysaccharide with many beneficial properties. Sulfated xanthan derivatives have anticoagulant and antithrombotic activity. This work proposes a new method for the synthesis of xanthan sulfates using sulfamic acid. Various N-substituted ureas have been investigated as process activators. It was found that urea has the greatest activating ability. BBD of xanthan sulfation process with sulfamic acid in 1,4-dioxane has been carried out. It was shown that the optimal conditions for the sulfation of xanthan (13.1 wt% sulfur content) are: the amount of sulfating complex per 1 g of xanthan is 3.5 mmol, temperature 90 °C, duration 2.3 h. Sulfated xanthan with the maximum sulfur content was analyzed by physicochemical methods. Thus, in the FTIR spectrum of xanthan sulfate, in comparison with the initial xanthanum, absorption bands appear at 1247 cm−1, which corresponds to the vibrations of the sulfate group. It was shown by GPC chromatography that the starting xanthan gum has a bimodal molecular weight distribution of particles, including a high molecular weight fraction with Mw > 1000 kDa and an LMW fraction with Mw < 600 kDa. It was found that the Mw of sulfated xanthan gum has a lower value (~612 kDa) in comparison with the original xanthan gum, and a narrower molecular weight distribution and is characterized by lower PD values. It was shown by thermal analysis that the main decomposition of xanthan sulfate, in contrast to the initial xanthan, occurs in two stages. The DTG curve has two pronounced peaks, with maxima at 226 and 286 °C.

A deep eutectic solvent (DES) composed of sulfamic acid and glycerol allowed for the sustainable preparation of cellulose nanofibrils (CNF) with simultaneous sulfation. The reaction time and the levels of sulfamic acid demonstrated that fibers could be swelled and sulfated simultaneously by a sulfamic acid-glycerol-based DES and swelling also promoted sulfation with a high degree of substitution (0.12). The DES-pretreated fibers were further nanofibrillated by a grinder producing CNF with diameters from 10 nm to 25 nm. The crystallinity ranged from 53–62%, and CNF maintained the original crystal structure. DES pretreatment facilitated cellulose nano-fibrillation and reduced the energy consumption with a maximum reduction of 35%. The films prepared from polyvinyl alcohol (PVA) and CNF showed good UV resistance ability and mechanical properties. This facile and efficient method provided a more sustainable strategy for the swelling, functionalization and nano-fibrillation of cellulose, expanding its application to UV-blocking materials and related fields.

The linear anionic class of polysaccharides, glycosaminoglycans (GAGs), are critical throughout the animal kingdom for developmental processes and the maintenance of healthy tissues. They are also of interest as a means of influencing biochemical processes. One member of the GAG family, heparin, is exploited globally as a major anticoagulant pharmaceutical and there is a growing interest in the potential of other GAGs for diverse applications ranging from skin care to the treatment of neurodegenerative conditions, and from the treatment and prevention of microbial infection to biotechnology. To realize the potential of GAGs, however, it is necessary to develop effective tools that are able to exploit the chemical manipulations to which GAGs are susceptible. Here, the current knowledge concerning the chemical modification of GAGs, one of the principal approaches for the study of the structure-function relationships in these molecules, is reviewed. Some additional methods that were applied successfully to the analysis and/or processing of other carbohydrates, but which could be suitable in GAG chemistry, are also discussed.

2,3-Dehydrosilybin A and 2,3-dehydrosilybin B are a pair of enantiomers formed by the oxidation of the natural flavonolignans silybin A and silybin B, respectively. However, the antioxidant activity of 2,3-dehydrosilybin molecules is much stronger than that of their precursors. Here, we investigated the biotransformation of pure 2,3-dehydrosilybin A and 2,3-dehydrosilybin B in isolated human hepatocytes, and we also aimed to identify human UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) with activity toward their respective enantiomers. After incubation with hepatocytes, both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B were converted to hydroxyl derivatives, methylated hydroxyl derivatives, methyl derivatives, sulfates, and glucuronides. The products of direct conjugations predominated over those of oxidative metabolism, and glucuronides were the most abundant metabolites. Furthermore, we found that recombinant human UGTs 1A1, 1A3, 1A7, 1A8, 1A9, and 1A10 were capable of catalyzing the glucuronidation of both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B. UGTs 1A1 and 1A7 showed the highest activity toward 2,3-dehydrosilybin A, and UGT1A9 showed the highest activity toward 2,3-dehydrosilybin B. The sulfation of 2,3-dehydrosilybin A and B was catalyzed by SULTs 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C2, 1C4, and 1E1, of which SULT1A3 exhibited the highest activity toward both enantiomers. We conclude that 2,3-dehydrosilybin A and B are preferentially metabolized by conjugation reactions, and that several human UGT and SULT enzymes may play a role in these conjugations.

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.

Vanillin-based lactoside derivatives were synthetized using phase-transfer catalyzed reactions from per-O-acetylated lactosyl bromide. The aldehyde group of the vanillin moiety was then modified to generate a series of related analogs having variable functionalities in the para- position of the aromatic residue. The corresponding unprotected lactosides, obtained by Zemplén transesterification, were regioselectively 3′-O-sulfated using tin chemistry activation followed by treatment with sulfur trioxide-trimethylamine complex (Men3N-SO3). Additional derivatives were also prepared from the vanillin’s aldehyde using a Knoevenagel reaction to provide extended α, β-unsaturated carboxylic acid which was next reduced to the saturated counterpart.

Cytosolic sulfotransferases (SULTs) catalyze phase II (conjugation) reactions of drugs and endogenous compounds. A complete set of recombinant fission yeast strains each expressing one of the 14 human SULTs was generated, including SULT4A1 and SULT6B1. Sulfation of test substrates by whole-cell biotransformation was successfully demonstrated for all enzymes for which substrates were previously known. The results proved that the intracellular production of the cofactor 3′-phosphoadenosine 5′-phosphosulfate (PAPS) necessary for SULT activity in fission yeast is sufficiently high to support metabolite production. A modified variant of sulfotransferase assay was also developed that employs permeabilized fission yeast cells (enzyme bags). Using this approach, SULT4A1-dependent sulfation of 1-naphthol was observed. Additionally, a new and convenient SULT activity assay is presented. It is based on the sulfation of a proluciferin compound, which was catalyzed by SULT1E1, SULT2A1, SULT4A1, and SULT6B1. For the latter two enzymes this study represents the first demonstration of their enzymatic functionality. Furthermore, the first catalytically competent homology models for SULT4A1 and SULT6B1 in complex with PAPS are reported. Through mechanistic molecular modeling driven by substrate docking, we pinned down the increased activity levels of these two isoforms to optimized substrate binding.

Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan (GAG) polysaccharide with a unique structure, displaying a backbone composed of alternating N-acetyl-d-galactosamine (GalNAc) and d-glucuronic acid (GlcA) units on which l-fucose (Fuc) branches are installed. fCS shows several potential biomedical applications, with the anticoagulant activity standing as the most promising and widely investigated one. Natural fCS polysaccharides extracted from marine organisms (Echinoidea, Holothuroidea) present some advantages over a largely employed antithrombotic drug such as heparin, but some adverse effects as well as a frequently found structural heterogeneity hamper its development as a new drug. To circumvent these drawbacks, several efforts have been made in the last decade to obtain synthetic and semi-synthetic fCS oligosaccharides and low molecular weight polysaccharides. In this Review we have for the first time collected these reports together, dividing them in two topics: (i) total syntheses of fCS oligosaccharides and (ii) semi-synthetic approaches to fCS oligosaccharides and low molecular weight polysaccharides as well as glycoclusters displaying multiple copies of fCS species.

The recovery of platinum group elements (PGE (platinum group element coating); Pd, Pt, and Rh) from used catalytic converters, using low energy and fewer chemicals, was developed using potassium bisulfate fusion pretreatment, and subsequently leached using hydrochloric acid. In the fusion pre-treatment, potassium bisulfate alone (without the addition of an oxidant) proved to be an effective and selective fusing agent. It altered PGE into a more soluble species and did not react with the cordierite support, based on X-Ray Diffraction (XRD) and metallographic characterization results. The fusion efficacy was due to the transformation of bisulfate into pyrosulfate, which is capable of oxidizing PGE. However, the introduction of potassium through the fusing agent proved to be detrimental, in general, since potassium formed insoluble potassium PGE chloro-complexes during leaching (decreasing the recovery) and required higher HCl concentration and a higher leaching temperature to restore the solubility. Optimization on the fusion and leaching parameter resulted in 106% ± 1.7%, 93.3% ± 0.6%, and 94.3% ± 3.9% recovery for Pd, Pt, and Rh, respectively. These results were achieved at fusion conditions: temperature 550 °C, potassium bisulfate/raw material mass ratio 2.5, and fusion time within 30 min. The leaching conditions were: HCl concentration 5 M, temperature 80 °C, and time within 20 min.

Natural anionic polysaccharides fucosylated chondroitin sulfates (FCS) from sea cucumbers attract great attention nowadays due to their ability to influence various biological processes, such as blood coagulation, thrombosis, angiogenesis, inflammation, bacterial and viral adhesion. To determine pharmacophore fragments in FCS we have started systematic synthesis of oligosaccharides with well-defined structure related to various fragments of these polysaccharides. In this communication, the synthesis of non-sulfated and selectively O-sulfated di- and trisaccharides structurally related to branching sites of FCS is described. The target compounds are built up of propyl β-d-glucuronic acid residue bearing at O-3 α-l-fucosyl or α-l-fucosyl-(1→3)-α-l-fucosyl substituents. O-Sulfation pattern in the fucose units of the synthetic targets was selected according to the known to date holothurian FCS structures. Stereospecific α-glycoside bond formation was achieved using 2-O-benzyl-3,4-di-O-chloroacetyl-α-l-fucosyl trichloroacetimidate as a donor. Stereochemical outcome of the glycosylation was explained by the remote participation of the chloroacetyl groups with the formation of the stabilized glycosyl cations, which could be attacked by the glycosyl acceptor only from the α-side. The experimental results were in good agreement with the SCF/MP2 calculated energies of such participation. The synthesized oligosaccharides are regarded as model compounds for the determination of a structure-activity relationship in FCS.

Sulfation is a common modification of extracellular glycans, tyrosine residues on proteins, and steroid hormones, and is important in a wide variety of signaling pathways. We investigated the role of sulfation on endogenous oxidative stress, such as glutamate-induced oxytosis and erastin-induced ferroptosis, using mouse hippocampal HT22 cells. Sodium chlorate competitively inhibits the formation of 3′-phosphoadenosine 5′-phosphosulfate, the high energy sulfate donor in cellular sulfation reactions. The treatment of HT22 cells with sodium chlorate decreased sulfation of heparan sulfate proteoglycans and chondroitin sulfate proteoglycans. Sodium chlorate and β-d-xyloside, which prevents proteoglycan glycosaminoglycan chain attachment, exacerbated both glutamate- and erastin-induced cell death, suggesting that extracellular matrix influenced oxytosis and ferroptosis. Moreover, sodium chlorate enhanced the generation of reactive oxygen species and influx of extracellular Ca2+ in the process of oxytosis and ferroptosis. Interestingly, sodium chlorate did not affect antioxidant glutathione levels. Western blot analysis revealed that sodium chlorate enhanced erastin-induced c-Jun N-terminal kinase phosphorylation, which is preferentially activated by cell stress-inducing signals. Collectively, our findings indicate that sulfation is an important modification for neuroprotection against oxytosis and ferroptosis in neuronal hippocampal cells.

Acid catalysis is quite prevalent and probably one of the most routine operations in both industrial processes and research laboratories worldwide. Recently, “graphene”, a two dimensional single-layer carbon sheet with hexagonal packed lattice structure, imitative of nanomaterials, has shown great potential as alternative and eco-friendly solid carbocatalyst for a variety of acid-catalyzed reactions. Owing to their exceptional physical, chemical, and mechanical properties, graphene-based nanomaterials (G-NMs) offer highly stable Brønsted acidic sites, high mass transfer, relatively large surface areas, water tolerant character, and convenient recoverability as well as recyclability, whilst retaining high activity in acid-catalyzed chemical reactions. This comprehensive review focuses on the chemistry of G-NMs, including their synthesis, characterization, properties, functionalization, and up-to-date applications in heterogeneous acid catalysis. In line with this, in certain instances readers may find herein some criticisms that should be taken as constructive and would be of value in understanding the scope and limitations of current approaches utilizing graphene and its derivatives for the same.

Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan found up to now exclusively in the body wall of sea cucumbers. It shows several interesting activities, with the anticoagulant and antithrombotic as the most attractive ones. Its different mechanism of action on the blood coagulation cascade with respect to heparin and the retention of its activity by oral administration make fCS a very promising anticoagulant drug candidate for heparin replacement. Nonetheless, its typically heterogeneous structure, the detection of some adverse effects and the preference for new drugs not sourced from animal tissues, explain how mandatory is to open an access to safer and less heterogeneous non-natural fCS species. Here we contribute to this aim by investigating a suitable chemical strategy to obtain a regioisomer of the natural fCS polysaccharide, with sulfated l-fucosyl branches placed at position O-6 of N-acetyl-d-galactosamine (GalNAc) units instead of O-3 of d-glucuronic acid (GlcA) ones, as in natural fCSs. This strategy is based on the structural modification of a microbial sourced chondroitin polysaccharide by regioselective insertion of fucosyl branches and sulfate groups on its polymeric structure. A preliminary in vitro evaluation of the anticoagulant activity of three of such semi-synthetic fCS analogues is also reported.

EPS-1 was an exopolysaccharide produced by the medicinal fungus Cordyceps sinensis (Cs-HK1). In the present study, EPS-1 was sulfated with chlorosulfonic acid (CSA)-pyridine (Pyr) at different volume ratios, yielding four sulfated derivatives, SEPS-1A, B, C and D, with different degrees of substitution (DS: 0.25–1.38) and molecular weights (17.1–4.1 kDa). The sulfation of EPS-1 occurred most frequently at the C-6 hydroxyl groups due to their higher reactivity. In aqueous solution, the native EPS-1 formed random coils or aggregated networks, but the sulfated derivatives formed single helices. The antioxidant activities of the sulfated EPS-1 derivatives for scavenging hydroxyl radicals (•OH) and 2,2-azinobis-3-ehtylbenzothiazolin-6-sulfonic acid radicals (ABTS•+) were significantly increased with increasing DS and decreasing molecular weight (MW). Sulfation has thus been shown to be an effective and favorable strategy for improving the physico-chemical properties and bioactivities of fungal polysaccharides.

Glucuronomannan oligosaccharides (Gs) were derived from fucoidan, which was extracted from the brown alga Sargassum thunbergii. Sulfated glucuronomannan oligosaccharides (SGs) were obtained by the sulfation of Gs. NMR techniques were used to reveal that the order of sulfation was Man-C6 > Man-C4 > Man-C1R > GlcA-C3 > Man-C3 > GlcA-C2. Finally, the antioxidant activities (hydroxyl radical scavenging activity, superoxide radical scavenging activity, reducing power and DPPH radical scavenging activity) of Gs and SGs were determined. The findings showed that the higher the degree of polymerization, the better the activity, except for the hydroxyl radical scavenging activity. In addition, the higher the sulfate content, the lower the activities for the reducing power and DPPH radical scavenging activity. Opposite results were found for the superoxide radical scavenging activity. Finally, compared with fucoidan, most Gs and SGs had higher antioxidant activity, suggesting that they might be good candidates for antioxidants.

The aging mechanisms of lead-acid batteries change the electrochemical characteristics. For example, sulfation influences the active surface area, and corrosion increases the resistance. Therefore, it is expected that the state of health (SoH) can be reflected through differentiable changes in the impedance of a lead-acid battery. However, for lead-acid batteries, no reliable SoH algorithm is available based on single impedance values or the spectrum. Additionally, the characteristic changes of the spectrum during aging are unknown. In this work, lead-acid test cells were aged under specific cycle regimes known as AK3.4, and periodic electrochemical impedance spectroscopy (EIS) measurements and capacity tests were conducted. It was examined that single impedance values increased linearly with capacity decay, but with varying slopes depending on the pre-history of the cell and measurement frequency of impedance. Thereby, possible reasons for ineffective SoH estimation were found. The spectra were fitted to an equivalent electrical circuit containing, besides other elements, an ohmic and a charge-transfer resistance of the negative electrode. The linear increase of the ohmic resistance and the charge-transfer resistance were characterized for the performed cyclic aging test. Results from chemical analysis confirmed the expected aging process and the correlation between capacity decay and impedance change. Furthermore, the positive influence of charging on the SoH could be detected via EIS. The results presented here show that SoH estimation using EIS can be a viable technique for lead-acid batteries.

Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were first evaluated in vitro on human and murine osteosarcoma cell lines. Different biological activities were studied: cell proliferation, cell adhesion and migration, matrix metalloproteinase expression. This in vitro study showed that only the OS-EPS 15 kDa derivative could inhibit the invasiveness of osteosarcoma cells with an inhibition rate close to 90%. Moreover, this derivative was potent to inhibit both migration and invasiveness of osteosarcoma cell lines; had no significant effect on their cell cycle; and increased slightly the expression of MMP-9, and more highly the expression of its physiological specific tissue inhibitor TIMP-1. Then, the in vivo experiments showed that the OS-EPS 15 kDa derivative had no effect on the primary osteosarcoma tumor induced by osteosarcoma cell lines but was very efficient to inhibit the establishment of lung metastases in vivo. These results can help to better understand the mechanisms of GAGs and GAG-like derivatives in the biology of the tumor cells and their interactions with the bone environment to develop new therapeutic strategies.