Sugar-Based Surfactants: Effects of Structural Features on the Physicochemical Properties of Sugar Esters and Their Comparison to Commercial Octyl Glycosides.

Two series of sugar esters with alkyl chain lengths varying from 5 to 12 carbon atoms, and with a head group consisting of glucose or galactose moieties, were synthesized. Equilibrium surface tension isotherms were measured, yielding critical micellar concentration (CMC) surface tensions at CMC (γcmc) and minimum areas at the air-water interface (Amin). In addition, Krafft temperatures (Tks) were measured to characterize the ability of molecules to dissolve in water, which is essential in numerous applications. As a comparison to widely used commercial sugar-based surfactants, those measurements were also carried out for four octyl d-glycosides. Impacts of the linkages between polar and lipophilic moieties, alkyl chain lengths, and the nature of the sugar head group on the measured properties were highlighted. Higher Tk and, thus, lower dissolution ability, were found for methyl 6-O-acyl-d-glucopyranosides. CMC and γcmc decreased with the alkyl chain lengths in both cases, but Amin did not appear to be influenced. Both γcmc and Amin appeared independent of the ester group orientation. Notably, alkyl (methyl α-d-glucopyranosid)uronates were found to result in noticeably lower CMC, possibly due to a closer distance between the carbonyl function and the head group.

Impact of the chemical structure on amphiphilic properties of sugar-based surfactants: A literature overview.

In this review, structure-property trends are systematically analyzed for four amphiphilic properties of sugar-based surfactants: critical micelle concentration (CMC), its associated surface tension (γCMC), efficiency (pC20) and Krafft temperature (TK). First, the impact on amphiphilic properties of the alkyl chain size and the presence of branching and/or unsaturation is investigated. Then, various polar head parameters are explored, such as the degree of polymerization of the sugar unit (mono- or oligosaccharides), the chemical nature of the linker and the sugar configuration. Some systematic comparisons between ethoxylated surfactants and sugar-based surfactants are also carried out. While some structural trends with the impact of alkyl chain length or the polar head size are now well understood, this analysis points out that systematic studies of more specific effects of alkyl chain (e.g. branching, unsaturation, presence of rings, position on the polar head) and polar head (e.g. linker, anomeric configuration, internal stereochemistry, cyclic vs. acyclic sugar residues) were scarcer or not available to date. This work encourages the use of these structural trends in the perspective of developing new bio-based surfactants and their consideration in predictive models. It also highlights the need of further experimental tests to fill remaining gaps notably to explore some specific structural features (such as the introduction of rings in the alkyl chain or the position of the alkyl chain on the polar head) and towards applicative properties (like foaming capacity or wettability).

Lactose derivatives as potential inhibitors of pectin methylesterases.

The discovery of molecules that can inhibit the action of phytopathogens is essential to find alternative to current pesticides. Pectin methylesterases (PME), enzymes that fine-tune the degree of methylesterification of plant cell wall pectins, play a key role in the pathogenicity of fungi or bacteria. Here we report the synthesis of new lactoside derivatives and their analysis as potential PME inhibitors using three plants and one fungal PME. Because of its structure, abundance and reduced cost, lactose was chosen as a case study. Lactoside derivatives were obtained by TEMPO-mediated oxidation of methyl lactoside, followed by an esterification procedure. Three derivatives were synthesized: sodium (methyl-lactosid)uronate, methyl (methyl-lactosid)uronate and butyl (methyl-lactosid)uronate. The inhibition of the plant and pathogen enzyme activities by lactoside derivatives was measured in vitro, showing the importance of the substitution on lactose: methyl (methyl-lactosid)uronate was more efficient than butyl (methyl-lactosid)uronate. These results were confirmed by docking analysis showing the difference in the interaction between lactoside derivatives and PME proteins. In conclusion, this study identified novel inhibitors of pectin remodeling enzymes.

Nitroxide supported on nanometric metal oxides as new hybrid catalysts for selective sugar oxidation.

A new series of supported organocatalysts, prepared by a simple method, were used for selective sugar oxidation. This approach is based on the immobilization of a nitroxide derivative through a carboxylic function on nanometric metal oxides (TiO2, Al2O3 and CeO2), allowing the recovery of the catalyst. These hybrid materials were carefully characterized by Diffuse Reflectance FT-IR spectroscopy (DRIFT), ThermoGravimetric Analysis (TGA), X-Ray Diffraction (XRD), Brunauer-Emmet-Teller surface area measurements (B.E.T.), elemental and electrochemical analyses, showing different characteristics and behaviors depending on the nature of the metal oxide used. The activity of the supported nitroxide catalyst was evaluated on methyl α-d-glucoside oxidation, used as model reaction. In all cases, high catalytic activity was highlighted, with up to 25 times less nitroxyl radical required for complete conversion than under homogeneous conditions. The influence of several experimental conditions such as the use of phosphate buffer and recyclability of the catalyst were also investigated.

Structural characterization and rheological behavior of a heteroxylan extracted from Plantago notata Lagasca (Plantaginaceae) seeds.

Plantago notata (Plantaginaceae) is a spontaneous plant from Septentrional Algerian Sahara currently used by traditional healers to treat stomach disorders, inflammations or wound healing. A water-soluble polysaccharide, called PSPN (PolySaccharide fraction from Plantago Notata), was extracted and purified from the seeds of this semi-arid plant. The structural features of this mucilage were evaluated by colorimetric assays, Fourier transformed infrared spectroscopy (FT-IR), gas chromatography coupled to mass spectrometry (GC/MS) and 1H/13C Nuclear Magnetic Resonance (NMR) spectroscopy. PSPN is a heteroxylan with a backbone composed of ß-(1,3)-d-Xylp and ß-(1,4)-d-Xylp highly branched, through (O)-2 and (O)-3 positions of ß-(1,4)-d-Xylp by various side chains and terminal monosaccharides such as α-l-Araf-(1,3)-ß-d-Xylp, ß-d-Xylp-(1,2)-ß-d-Xylp, terminal Xylp or terminal Araf. The physico-chemical and rheological analysis of this polysaccharide in dilute and semi diluted regimes showed that PSPN exhibites a molecular weight of 2.3×106g/mol and a pseudoplastic behavior.

Measurement of cytotoxicity and irritancy potential of sugar-based surfactants on skin-related 3D models.

Sugar-based surfactants present surface-active properties and relatively low cytotoxicity. They are often considered as safe alternatives to currently used surfactants in cosmetic industries. In this study, four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or a maltose headgroup through an amide linkage, were synthesized and compared to two standard surfactants. The cytotoxic and irritant effects of surfactants were evaluated using two biologically relevant models: 3D dermal model (mouse fibroblasts embedded in collagen gel) and reconstituted human epidermis (RHE, multi-layered human keratinocytes). Results show that three synthesized surfactants possess lower cytotoxicity compared to standard surfactants as demonstrated in the 3D dermal model. Moreover, the IC50s of surfactants against the 3D dermal model are higher than IC50s obtained with the 2D dermal model (monolayer mouse fibroblasts). Both synthesized and standard surfactants show no irritant effects after 48h of topical application on RHE. Throughout the study, we demonstrate the difficulty to link the physico-chemical properties of surfactants and their cytotoxicity in complex models. More importantly, our data suggest that, prior to in vivo tests, a complete understanding of surfactant cytotoxicity or irritancy potential requires a combination of cellular and tissue models.

Catalytic Synthesis of a New Series of Alkyl Uronates and Evaluation of Their Physicochemical Properties.

Large quantities (>3 g) of a new series of alkyl uronates were synthesized in two steps from commercial methyl hexopyranosides. Firstly, several tens of grams of free methyl α-d-glucopyranoside were selectively and quantitatively oxidized into corresponding sodium uronate using 2,2,6,6-tetramethyl-1-piperidinyloxy free radical (TEMPO)-catalyzed oxidation. Hydrophobic chains of different length were then introduced by acid-mediated esterification with fatty alcohols (ethyl to lauryl alcohol) leading to the desired alkyl glucuronates with moderate to good yields (49%-72%). The methodology was successfully applied to methyl α-d-mannopyranoside and methyl ß-d-galactopyranoside. Physicochemical properties, such as critical micelle concentration (CMC), equilibrium surface tension at CMC (γcmc), solubility, and Krafft temperature were measured, and the effect of structural modifications on surface active properties and micelle formation was discussed.

Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations.

Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels.

5-O-caffeoylshikimic acid from Solanum somalense leaves: advantage of centrifugal partition chromatography over conventional column chromatography.

Solanum somalense leaves, used in Djibouti for their medicinal properties, were extracted by MeOH. Because of the high polyphenol and flavonoid contents of the extract, respectively, determined at 80.80 ± 2.13 mg gallic acid equivalent/g dry weight and 24.4 ± 1.01 mg quercetin equivalent/g dry weight, the isolation and purification of the main polyphenols were carried out by silica gel column chromatography and centrifugal partition chromatography. Column chromatography led to 11 enriched fractions requiring further purification, while centrifugal partition chromatography allowed the easy recovery of the main compound of the extract. In a solvent system composed of CHCl3/MeOH/H2O (9.5:10:5), 21.8 mg of this compound at 97% purity was obtained leading to a yield of 2.63%. Its structure was established as 5-O-caffeoylshikimic acid by mass spectrometry and NMR spectroscopy. This work shows that S. somalense leaves contain very high level of 5-O-caffeoylshikimic acid (0.74% dry weight), making it a potential source of production of this secondary metabolite that is not commonly found in nature but could be partly responsible of the medicinal properties of S. somalense leaves.

Anti-biofilm activity: a function of Klebsiella pneumoniae capsular polysaccharide.

Competition and cooperation phenomena occur within highly interactive biofilm communities and several non-biocides molecules produced by microorganisms have been described as impairing biofilm formation. In this study, we investigated the anti-biofilm capacities of an ubiquitous and biofilm producing bacterium, Klebsiella pneumoniae. Cell-free supernatant from K. pneumoniae planktonic cultures showed anti-biofilm effects on most Gram positive bacteria tested but also encompassed some Gram negative bacilli. The anti-biofilm non-bactericidal activity was further investigated on Staphylococcus epidermidis, by determining the biofilm biomass, microscopic observations and agglutination measurement through a magnetic bead-mediated agglutination test. Cell-free extracts from K. pneumoniae biofilm (supernatant and acellular matrix) also showed an influence, although to a lesser extend. Chemical analyses indicated that the active molecule was a high molecular weight polysaccharide composed of five monosaccharides: galactose, glucose, rhamnose, glucuronic acid and glucosamine and the main following sugar linkage residues [→ 2)-α-L-Rhap-(1 →]; [→ 4)-α-L-Rhap-(1 →]; [α-D-Galp-(1 →]; [→ 2,3)-α-D-Galp-(1 →]; [→ 3)-ß-D-Galp-(1 →] and, [→ 4)-ß-D-GlcAp-(1 →]. Characterization of this molecule indicated that this component was more likely capsular polysaccharide (CPS) and precoating of abiotic surfaces with CPS extracts from different serotypes impaired the bacteria-surface interactions. Thus the CPS of Klebsiella would exhibit a pleiotropic activity during biofilm formation, both stimulating the initial adhesion and maturation steps as previously described, but also repelling potential competitors.

Norlittorine and norhyoscyamine identified as products of littorine and hyoscyamine metabolism by (13)C-labeling in Datura innoxia hairy roots.

The presence of two compounds, norlittorine and norhyoscyamine, has been reported in leaves and roots of Datura innoxia; however their metabolic origin in the tropane alkaloid pathway has remained unknown. Precise knowledge of this pathway is a necessary pre-requisite to optimize the production of hyoscyamine and scopolamine in D. innoxia hairy root cultures. The exact structure of norlittorine and norhyoscyamine was confirmed by LC-MS/MS and NMR analyses. Isotopic labeling experiments, using [1-(13)C]-phenylalanine, [1'-(13)C]-littorine and [1'-(13)C]-hyoscyamine, combined with elicitor treatments, using methyl jasmonate, coronalon and 1-aminocyclopropane-1-carboxylic acid, were used to investigate the metabolic origin of the N-demethylated tropane alkaloids. The results suggest that norlittorine and norhyoscyamine are induced under stress conditions by conversion of littorine and hyoscyamine. We propose the N-demethylation of tropane alkaloids as a mechanism to detoxify cells in overproducing conditions.

Synthesis and evaluation of sulfamide-type indolizidines as glycosidase inhibitors.

A practical synthesis of reducing sulfamide-derived iminosugar glycomimetics related to the indolizidine glycosidase inhibitor family is reported. The polyhydroxylated bicyclic system was built from readily accessible hexofuranose derivatives through a synthetic scheme that involves 5,6-cyclic sulfamides. Further intramolecular nucleophilic addition of the sulfamide nitrogen atom to the masked aldehyde group of the monosaccharide in the open chain form afforded the target sugar mimics. By starting from d-glucose and d-mannose precursors, 2-aza-3,3-dioxo-3-thiaindolizidine derivatives with hydroxylation profiles that matched those of (+)-castanospermine and 6-epi-(+)-castanospermine were obtained. In vitro screening against a panel of glycosidases evidenced a high selectivity towards alpha-mannosidase.

Efficient purification of small unsaturated oligoglucuronides by reversed-phase chromatography.

Ion-exchange chromatography has been applied to purification of unsaturated oligoglucuronans. After an isocratic elution on a strong anion-exchange column, the collected fractions were desalted by low pressure size exclusion chromatography. However, this efficient separation was limited by the time required to desalt. So, we developed a reversed-phase chromatography method using back ionization of oligomers. Two C18 columns were tested with trifluoroacetic acid (TFA 0.7%) as eluent. Different selectivities and column stabilities were observed in this acidic condition. The scale up for semi-preparative applications enabled us to recover pure unsaturated oligoglucuronans without desalting step.

Towards the synthesis of new benzimidazolone derivatives with surfactant properties.

New water-soluble benzimidazolone derivatives were synthesized. In the first approach, di-N-glycosyl and mono-N-alkyl-N-glycosyl compounds were obtained by grafting C-6-activated glycosides onto benzimidazolone. In the second approach, benzimidazolone derivatives bearing a glucosyl unit were synthesized using an efficient glycosylation method. Every compound structure was confirmed by means of NMR spectroscopy and elemental analysis. The preliminary surfactant properties of some compounds were evaluated.

Regioselective synthesis of 6-S-alkyl and 6-S-glycosyl-6-thio-D-mannofuranose derivatives from 5,6-O-cyclic sulfate precursors.

C-6 opening of 5,6-cyclic sulfate derivatives of mannofuranose with a thiolate anion followed by acidic hydrolysis of the acyclic sulfate gave 6-S-alkyl derivatives in good yields (70-95%) and short reaction times (10-15min). This methodology was applied to the synthesis of methyl 2,3-O-isopropylidene-6-S-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl)-6-thio-alpha-d-mannofuranoside (70%), 2,3-O-isopropylidene-6-S-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl)-6-thio-alpha-d-mannofuranose (87%) and 2,3-O-isopropylidene-6-S-(1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranos-6-yl)-6-thio-alpha-d-mannofuranose (87%).

Efficient in vitro regeneration of fertile plants from corm explants of Hypoxis hemerocallidea landrace Gaza -- the "African Potato".

We present efficient protocols for the regeneration of fertile plants from corm explants of Hypoxis hemerocallidea Fisch. and C. A. Mey. landrace Gaza, either by direct multiple shoot formation or via shoot organogenesis from corm-derived calluses. The regeneration efficiency depended on plant growth regulator concentrations and combinations. Multiple direct shoot formation with high frequency (100% with 5-8 shoots/explant) was obtained on a basal medium (BM) supplemented with 3 mg/l kinetin (BM1). However, efficient indirect regeneration occurred when corm explants were first plated on callus induction medium (BM2) with high kinetin (3 mg/l) and naphthalene acetic acid (NAA 1 mg/l), and then transferred to shoot inducing medium (BM3) containing BA (1.5 mg/l) and NAA (0.5 mg/l). Shoot regeneration frequency was 100% and 30-35 shoots per explant were obtained. The regenerated shoots were rooted on a root inducing medium (BM4) containing NAA (0.1 mg/l). Rooted plantlets were transferred to the greenhouse. The regenerants were morphologically normal and fertile. Flow cytometric analyses and chloroplast counts of guard cells suggested that the regenerants were diploid. Efficient cloning protocols described here, have the potential not only to substantially reduce the pressure on natural populations but also for wider biotechnological applications of Hypoxis hemerocallidea-an endangered medicinal plant.

A novel stereospecific synthesis of glycosyl cyanides from 1,2-O-sulfinyl derivatives.

[reaction: see text] An efficient synthesis of 1,2-trans-glycosyl cyanides via 1,2-O-sulfinyl monosaccharides is described. Such S(N)2-type displacements at the anomeric center are stereospecific and are best performed with sodium cyanide in the presence of ytterbium triflate. Significantly, the resulting 1,2-trans-glycosyl cyanides have a free hydroxyl group at C-2 ready for further modification.

Effect of phenolic glycosides on Agrobacterium tumefaciens virH gene induction and plant transformation.

O-Aryl-d-glucoside (4-7) and d-xyloside (8-10) derivatives were synthesized and tested on Agrobacterium virH gene induction and plant transformation. alpha- or beta-Glycosides enhanced vir activity at concentrations above 250 micromicro. The highest vir activity was observed with beta-glucoside derivative 4 at 10 mM. A marked difference between phenol glucoside derivative 4 and the corresponding free phenol on the growth of transformants was observed. The regenerated transgenic tissues, after transformation on medium containing acetosyringyl beta-glucoside 4, grew at twice the rate of those on medium containing only free acetosyringone (AS). Compound 4 was less toxic for tobacco explants compared to the corresponding free phenol. However, the xyloside derivatives tested (8-10) were less effective for gene induction compared with corresponding free phenols.