Total synthesis of the hexasaccharide arabinan domain of mycobacterial arabinogalactan.

The hexasaccharide arabinan domain of Mycobacterial Arabinogalactan was provided with the versatile methodology toward ß-selective arabinofuranosylation directed by B(C6F5)3, demonstrating the effectiveness of the ß-arabinofuranosylation strategy. Derivatization of the amino moiety at the reducing end are essential prerequisites for elucidating the biosynthetic pathway and conjugating of this compound to a protein carrier for vaccine generation.

Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant. Two gas generating agent (s) incorporated were sodium bicarbonate and citric acid. All compendial pre and post-compression tests results were in the acceptable limits. FTIR analysis confirmed drug-polymer compatibility. The in-vitro drug release in simulated conditions i.e., 0.1 N HCl for 12 h revealed orderly increase in total floating time, i.e., less than 6 h for F1 over 12 h for F9. Formulations F1 to F4 were not capable to retard drug release up to 12 h, whereas F5-F7 for 12 h, while F8 and F9 for more than 12 h. Data fitting in various kinetic models showed that drug release best fit in first order kinetic model and F9 in zero order. Based on results data, F7 was the best among all.

Research progress in galactomannan-based nanomaterials: Synthesis and application.

Galactomannans are naturally occurring biocompatible and biodegradable nonionic polysaccharides comprised of mannose and galactose residues. They are under investigation for the design of various drug delivery carriers such as matrix tablets, microparticles, nanoparticles/nanocomposites, polymeric micelles, hydrogels, as well as pharmaceutical excipients. Amongst galactomannans, guar gum, locust bean gum, and fenugreek gum are the biomaterials mostly investigated for their potential utility as nanocarriers for various purposes, either in their native or modified forms. The galactomannan-based nanomaterials have been fabricated by adopting various strategies. These galactomannan nanomaterials have been tested for oral vaccination, oral insulin delivery, cancer cell & macrophage targeting, controlled drug delivery, heavy metal extraction and wound dressing applications. The galactomannan has attracted the attention of researchers as reducing agents for the green synthesis of metal nanoparticles as well. These nanometals have shown improved antimicrobial, antioxidant and anticancer activities. In vitro toxicity of the nanomaterials is also assessed in some instances. Others such as cassia gum, tara gum, Delonix, Leucaena leucocephala, Punica granatum galactomannans are amongst the least studied materials for biological applications. This review describes various strategies adopted for the synthesis of galactomannan-based nanomaterials, their properties and applications, especially in the field of drug delivery.

Synthesis of quaternised guar gum using Taguchi L(16) orthogonal array.

Quaternised polysaccharides have diverse applications due to introduction of quaternary ammonium groups in the biopolymer. In the present study, quaternization of guar gum was carried out by adopting the Taguchi's approach of robust design of experiments for optimizing the levels of the factors to obtain quaternized guar gum with higher DS. The methodology employed far less number of experiments than the classical method which necessitates higher number of chemical reactions to achieve the required derivatisation. The application of Taguchi's L16 (45) orthogonal array resulted in DS of 0.49. The optimized experimental levels were 3.24 mol/AGU of NaOH and 2.04 mol/AGU of CHPTAC for 2 h at 30 °C keeping the gum: liquor ratio 1:20. The study established that Taguchi methodology provided a statistically sound and green approach for optimization of reaction conditions. The modified products were characterised by FTIR, 1H-NMR, 13C-NMR, DEPT-135, HSQC and HMBC spectroscopic methods.

Guar gum cinnamate ouzo nanoparticles for bacterial contact killing in water environment.

Herein we report the synthesis of newer guar gum cinnamate esters (GGC) following a Hofmeister cation guided homogeneous phase reaction. High degree of substitution (DS) guar gum cinnamate was obtained using, cinnamic acid halide reactant at a 1:3 M ratio. The biopolymer was fully characterized in FT-IR,13C NMR, XRD and thermal analysis. Nanoparticles were further developed in a facile ouzo solvent diffusion technique. SEM studies confirmed quasi spherical shape of the nanoparticles (GGCN) with an average size of 200 nm. Nanoparticles GGCN, expressed antibacterial activity against water borne gram negative and gram positive bacteria. The MIC was recorded at 300 µg mL-1against Escherichia coli and 500 µg mL-1against Staphylococcus aureus. Bacterial contact killing was confirmed from the bacterial morphology studies in SEM. Thus, nanoparticles from GGC may be employed for bacterial killing and water decontamination.

Synthesis and Structural Analysis of Aspergillus fumigatus Galactosaminogalactans Featuring α-Galactose, α-Galactosamine and α-N-Acetyl Galactosamine Linkages.

Galactosaminogalactan (GAG) is a prominent cell wall component of the opportunistic fungal pathogen Aspergillus fumigatus. GAG is a heteropolysaccharide composed of α-1,4-linked galactose, galactosamine and N-acetylgalactosamine residues. To enable biochemical studies, a library of GAG-fragments was constructed featuring specimens containing α-galactose-, α-galactosamine and α-N-acetyl galactosamine linkages. Key features of the synthetic strategy include the use of di-tert-butylsilylidene directed α-galactosylation methodology and regioselective benzoylation reactions using benzoyl-hydroxybenzotriazole (Bz-OBt). Structural analysis of the Gal, GalN and GalNAc oligomers by a combination of NMR and MD approaches revealed that the oligomers adopt an elongated, almost straight, structure, stabilized by inter-residue H-bonds, one of which is a non-conventional C-H⋅⋅⋅O hydrogen bond between H5 of the residue (i+1) and O3 of the residue (i). The structures position the C-2 substituents almost perpendicular to the oligosaccharide main chain axis, pointing to the bulk solvent and available for interactions with antibodies or other binding partners.

Sonication-assisted synthesis of a new heterostructured schiff base ligand Silver-Guar gum encapsulated nanocomposite as a visible light photocatalyst.

A heterostructured Schiff base ligand (Benzildiethylenetriamine)-Silver-Guar gum encapsulated nanocomposites was intended to prepare by simple sonication assisted reflux method. Appropriate composition of purified guar gum, Schiff base ligand and silver nitrate were used for the synthesis. The synthesised nanocomposites were characterised by photoluminescence spectrum, UV-vis diffuse reflectance spectrophotometer, Fourier transform infra-red spectroscopy, X-ray diffractometer, scanning electron microscopy and transmission electron microscopy. The crystalline peaks of XRD and FTIR reveals that Schiff base ligand and guar gum forms metal-organic matrix. Morphology studies have confirmed the organic framework structure and metallic silver nanoparticles are embedded on the organic framework. The efficiency of nanocomposites depends on adsorption capacity and silver nanoparticles that are encapsulated thereby increasing the visible light absorption through surface plasma resonance. The nanocomposite was proved to be highly selective in hydrogenation reaction which favoured the formation of aniline from nitrobenzene as single product with short reaction time and 90% conversion.

Sonochemical synthesis of gum guar biopolymer stabilized copper oxide on exfoliated graphite: Application for enhanced electrochemical detection of H2O2 in milk and pharmaceutical samples.

A novel and cost-effective synthesis of biopolymer-based organic and inorganic composite materials have received substantial attention in a broad range application including electroanalysis of small molecules. In this perspective, we report the synthesis of gum guar (guar) biopolymer stabilized cupric oxide decorated on exfoliated graphite (GR-guar/CuO) composite. Different physicochemical characterization methods were used to confirm the successful exfoliation of graphite and formation of the GR-guar/CuO composite. A simple sonochemical method has been used for the preparation of guar stabilized exfoliated graphite (GR-guar). The flower-like CuO on GR-guar and guar stabilized CuO (CuO-guar) composites were synthesized using a hydrothermal method. Cyclic voltammetric studies revealed that the GR-guar/CuO composite modified screen-printed carbon electrode (SPCE) had enhanced electro-reduction ability towards H2O2 than GR-guar and pristine graphite/CuO-guar modified SPCEs. Under optimized experimental conditions, the GR-guar/CuO composite modified electrode detects H2O2 in the response ranges from 0.02 to 1296.6 µM. The sensor shows a lower detection limit of 5.8 nM with high sensitivity. The as-prepared GR-guar/CuO composite sensor is highly reproducible and had excellent selectivity and practicality towards the detection of H2O2. Consequently, the fabricated sensor can be used for the accurate detection of H2O2 in real samples.

Synthesis and characterization of biopolymer based hybrid hydrogel nanocomposite and study of their electrochemical efficacy.

A highly competent material, based on poly lactic acid (PLLA) grafted hydroxypropyl guar gum (HPG-g-PLLA) and polypyrrole/carboxylated multiwalled carbon nanotube (PPy/C-MWCNT) composite of various binary composition and copolymer of one of these nanocomposites have been synthesized successfully by in-situ polymerization. The environmentally affable nanocomposites have been characterized by spectroscopy, microscopy and thermogravimetry. Cytotoxicity of bio-nanocomposite has been inquired by cell viability study, which reveals its eco-friendly nature. The electrochemical properties of the biomaterials have been appraised by cyclic voltammetric studies. The PPy/C-MWCNT composite having 1 wt% C-MWCNT appears as the optimum composition from electrochemical studies. The hydrogel nanocomposite (HPG-g-PLLA5/0.5) copolymer behaves as a super ordinate material than pure PPy and PPy/C-MWCNT in every aspect of electrochemical properties like current density, stability, processibility and reversibility. Moreover the hydrogel nanocomposite, making electrode fabrication more simple and binder-free, nullifies all the interfacial complications arising from binders as well.

Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery.

Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.

Yariv reactivity of type II arabinogalactan from larch wood.

Larch arabinogalactan (AG) is classified as a plant type II AG. Its basic structure is constituted by a ß-1,3-galactan main chain with ß-1,6-galactan side chains. But its properties are distinct from other type II AGs. Whereas most type II AGs are found as glycan moieties of arabinogalactan-protein (AGP), larch AG lacks a protein moiety. Larch AG itself is also unlike other type II AGs as it lacks Yariv reactivity, the capability of AG to form insoluble precipitate with ß-Yariv reagents, 1,3,5-tri-(p-glycosyloxyphenylazo)-2,4,6-trihydroxybenzene with ß-glucosyl or ß-galactosyl residues at the termini. For the present study, we prepared ß-galactan I, II, and III from larch AG by performing single, double, and triple Smith degradation, which breaks ß-1,6-galactan side chains, and examined Yariv reactivity of the products. Methylation analysis revealed that ß-galactans II and III had lost more than 90% of their ß-1,6-galactan branches. In the radial gel diffusion assay, ß-galactans II and III showed Yariv reactivity, indicating the presence of a Yariv-reactive structure in larch AG, although native larch AG does not have Yariv reactivity. The Yariv reactivity of the ß-galactans was completely lost after treatment with endo-ß-1,3-galactanase. These results confirm that ß-1,3-galactan is necessary for Yariv reactivity of type II AG. The present results also suggest that high substitution of ß-1,3-galactan with ß-1,6-galactan side chains affects Yariv reactivity in larch AG.

Selenium incorporated guar gum nanoparticles safeguard mitochondrial bioenergetics during ischemia reperfusion injury in H9c2 cardiac cells.

The application of nanotechnology has created high impact in diagnosis and prognosis of various disorders including cardiovascular diseases. In the present study, we investigated the beneficial effect of selenium incorporated guar gum nanoparticles (SGG) compared to nascent selenium (Se) and guar gum nanoparticles (GGN) against ischemiareperfusion (IR) induced alterations in oxidative phosphorylation and energy metabolism in H9c2 cardiac cells. Ischemia and reperfusion were induced for 1h. The alterations in activities of various complexes (complex 1, II, III and IV) of mitochondrial electron transport chain (ETC), aconitase activity, oxygen consumption rate, and the ATP content were seen. The role of heat shock protein, hypoxia inducible factor-1α and atrial natriuretic factor (ANP) were also analyzed. Then the beneficial properties of various particles like Se, GGN and SGG were evaluated. Among these, SGG treatment (1 and 5ng) was found to be more beneficial compared to other particles. Overall results reveal that SGG nanoparticles are effective in protecting H9c2 cardiac cells from IR injury via improving the efficiency of ETC in H9c2 cells.

Synthesis and Application of Branched Type II Arabinogalactans.

The synthesis of linear and (1 → 6)-branched ß-(1 → 3)-d-galactans, structures found in plant arabinogalactan proteins (AGPs), is described. The synthetic strategy relies on iterative couplings of monosaccharide and disaccharide thioglycoside donors, followed by a late-stage glycosylation of heptagalactan backbone acceptors to introduce branching. A key finding from the synthetic study was the need to match protective groups in order to tune reactivity and ensure selectivity during the assembly. Carbohydrate microarrays were generated to enable the detailed epitope mapping of two monoclonal antibodies known to recognize AGPs: JIM16 and JIM133.

Determination of the Degree of Substitution of Cationic Guar Gum by Headspace-Based Gas Chromatography during Its Synthesis.

This study reports on a headspace-based gas chromatography (HS-GC) technique for determining the degree of substitution (DS) of cationic guar gum during the synthesis process. The method is based on the determination of 2,3-epoxypropyltrimethylammonium chloride in the process medium. After a modest pretreatment procedure, the sample was added to a headspace vial containing bicarbonate solution for measurement of evolved CO2 by HS-GC. The results showed that the method had a good precision (relative standard deviation of <3.60%) and accuracy for the 2,3-epoxypropyltrimethylammonium chloride measurement, with recoveries in the range of 96-102%, matching with the data obtained by a reference method, and were within 12% of the values obtained by the more arduous Kjeldahl method for the calculated DS of cationic guar gum. The HS-GC method requires only a small volume of sample and, thus, is suitable for determining the DS of cationic guar gum in laboratory-scale process-related applications.

Size Matters: Chemical Synthesis of a Homogenous Arabinogalactan 92-mer.

31+30+31: Ye and colleagues have synthesized a branched 92-mer of arabinogalactan-a major component of the cell wall of M. tuberculosis-by linking a linear oligogalactan 30-mer with two d-arabinofuranose 31-mers. Their approach capitalizes on sequential, one-pot glycosylation reactions that result in a rapid increase in molecular complexity and efficient synthesis of a branched oligosaccharide.

Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units.

Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent [31+31+30] coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.

Synthesis of 2-alkenyl-3-butoxypropyl guar gum with enhanced rheological properties.

A new guar gum derivative was synthesized though the nucleophilic substitution of sodium hydroxide-activated guar gum with n-butyl glycidyl (BGE) ether. The physicochemical properties of 2-alkenyl-3-butoxypropyl guar gum (ABPG) were characterized by attenuated total reflection Fourier transform infrared spectrometry (ATR-FTIR), X-ray diffraction (XRD) and thermal gravimetric analyses (TGA). The results showed that sodium hydroxide can be effectively substituted with BGE to form the ABPG. The steady and dynamic rheological properties of the aqueous solution and ABPG gel were determined using an RS6000 rheometer. Compared with the guar gum, ABPG enhanced the thickening property and improved the solution stability. The ABPG gel exhibited good temperature resistance and shear stability properties.

[Au]/[Ag]-catalysed expedient synthesis of branched heneicosafuranosyl arabinogalactan motif of Mycobacterium tuberculosis cell wall.

Emergence of multidrug-resistant and extreme-drug-resistant strains of Mycobacterium tuberculosis (MTb) can cause serious socioeconomic burdens. Arabinogalactan present on the cellular envelope of MTb is unique and is required for its survival; access to arabinogalactan is essential for understanding the biosynthetic machinery that assembles it. Isolation from Nature is a herculean task and, as a result, chemical synthesis is the most sought after technique. Here we report a convergent synthesis of branched heneicosafuranosyl arabinogalactan (HAG) of MTb. Key furanosylations are performed using [Au]/[Ag] catalysts. The synthesis of HAG is achieved by the repetitive use of three reactions namely 1,2-trans furanoside synthesis by propargyl 1,2-orthoester donors, unmasking of silyl ether, and conversion of n-pentenyl furanosides into 1,2-orthoesters. Synthesis of HAG is achieved in 47 steps (with an overall yield of 0.09%) of which 21 are installation of furanosidic linkages in a stereoselective manner.

Preparation of the tri-arabino di-mycolate fragment of mycobacterial arabinogalactan from defined synthetic mycolic acids.

An efficient synthetic approach to tri-arabino di-mycolates, using structurally defined synthetic α-, keto and methoxy mycolic acids is described.

Synthesis, characterization, and self-assembly with plasmid DNA of a quaternary ammonium derivative of pectic galactan and its fluorescent labeling for bioimaging applications.

Quaternized derivatives of pectic galactan (QPG) were synthesized by a reaction of pectic galactan (PG) with 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHPTAC) in the presence of aqueous sodium hydroxide solution under mild reaction conditions. The results showed that the concentration of CHPTAC and NaOH has great impact on the quaternization reaction. QPG was found to interact electrostatically with plasmid DNA in aqueous solution to form complexes in globular condensed morphology in a nanometer scale size ranging from 60 to 160nm. Complexes formed with QPG fluorescently labeled with 5-DTAF (QPG-5-DTAF) were introduced to the C6 rat glioma cell line, and were found to be able to enter the cell and approach the nucleus within 24h. The results suggest that this type of modified natural polysaccharide may have an advantage as a biocompatible and biodegradable gene delivery carrier and furthermore may serve as a cell specific carrier.