Laboratoire de Glycochimie, des Antimicrobiens
et des Agroressources UMR 7378 CNRS


Nos tutelles

  • Tutelle du CNRS
  • Tutelle UPJV

Nos Fédérations


Production Scientifique 2015-2020

Cyclodextrin complexation studies as the first step for repurposing of chlorpromazine
Wang, Z.; Landy, D.; Sizun, C.; Cézard, C.; Solgadi, A.; Przybylski, C.; de Chaisemartin, L.; Herfindal, L.; Barratt, G.; Legrand, F.-X.
Int. J. Pharm. 2020, 584, 119391.
The antipsychotic drug chlorpromazine (CPZ) has potential for the treatment of acute myeloid leukemia, if central nervous system side-effects resulting from its passage through the blood–brain barrier can be prevented. A robust drug delivery system for repurposed CPZ would be drug-in-cyclodextrin-in-liposome that would redirect the drug away from the brain while avoiding premature release in the circulation. As a first step, CPZ complexation with cyclodextrin (CD) has been studied. The stoichiometry, binding constant, enthalpy, and entropy of complex formation between CPZ and a panel of CDs was investigated by isothermal titration calorimetry (ITC). All the tested CDs were able to include CPZ, in the form of 1:1, 1:2 or a mixture of 1:1 and 1:2 complexes. In particular, a substituted γ-CD, sugammadex (the octasodium salt of octakis(6-deoxy-6-S-(2-carboxyethyl)-6-thio)cyclomaltooctaose), formed exclusively 1:2 complexes with an extremely high association constant of 6.37 × 109 M−2. Complexes were further characterized by heat capacity changes, one- and two-dimensional (ROESY) nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations. Finally, protection of CPZ against photodegradation by CDs was assessed. This was accelerated rather than reduced by complexation with CD. Altogether these results provide a molecular basis for the use of CD in delayed release formulations for CPZ.

Development of C-type lectin-oriented surfaces for high avidity glycoconjugates: towards mimicking multivalent interactions on the cell surface
Porkolab, V.; Pifferi, C.; Sutkeviciute, I.; Ordanini, S.; Taouai, M.; Thepaut, M.; Vivès, C.; Benazza, M.; Bernardi, A.; Renaudet, O.; Fieschi, F.
Org. Biomol. Chem. 2020.
Multivalent interactions between complex carbohydrates and oligomeric C-type lectins govern a wide range of immune responses. Up to date, standard SPR (surface plasmon resonance) competitive assays have largely been to evaluate binding properties from monosaccharide units (low affinity, mM) to multivalent elemental antagonists (moderate affinity, µM). Herein, we report typical case-studies of SPR competitive assays showing that they underestimate the potency of glycoclusters to inhibit the interaction between DC-SIGN and immobilized glycoconjugates. This paper describes the design and implementation of a SPR direct interaction over DC-SIGN oriented surfaces, extendable to other C-type lectin surfaces as such Langerin. This setup provides an overview of intrinsic avidity generation emanating simultaneously from multivalent glycoclusters and from DC-SIGN tetramers organized in nanoclusters at the cell membrane. To do so, covalent biospecific capture of DC-SIGN via StreptagII /StrepTactin interaction preserves tetrameric DC-SIGN, accessibility and topology of its active sites, that would have been dissociated using standard EDC-NHS procedure under acidic conditions. From the tested glycoclusters libraries, we demonstrated that the scaffold architecture, the valency and the glycomimetic-based ligand are crucial to reach nanomolar affinities for DC-SIGN. The glycocluster 3.D illustrates the tightest binding partner in this set for a DC-SIGN surface (KD= 18 nM). Moreover, the selectivity at monovalent scale of glycomimetic D can be easily analyzed at multivalent scale comparing its binding over different C-type lectin immobilized surfaces. This approach may give rise to novel insights into the multivalent binding mechanisms responsible for avidity and make a major contribution to the full characterization of the binding potency of promising specific and multivalent immodulators.

New Lipidyl-Cyclodextrins Obtained by Ring Opening of Methyl Oleate Epoxide Using Ball Milling
Oliva, E.; Mathiron, D.; Rigaud, S.; Monflier, E.; Sevin, E.; Bricout, H.; Tilloy, S.; Gosselet, F.; Fenart, L.; Bonnet, V.; Pilard, S.; Djedaini-Pilard, F.
Biomolecules 2020, 10, 339.
Bearing grafts based on fatty esters derivatives, lipidyl-cyclodextrins (L-CDs) are compounds able to form water-soluble nano-objects. In this context, bicatenary biobased lipidic-cyclodextrins of low DS were easily synthesized from a fatty ester epoxide by means of alternative methods (ball-milling conditions, use of enzymes). The ring opening reaction of methyl oleate epoxide needs ball-milling and is highly specific of cyclodextrins in solventless conditions. L-CDs are thus composed of complex mixtures that were deciphered by an extensive structural analysis using mainly mass spectrometry and NMR spectroscopy. In addition, as part of their potential use as vectors of active drugs, these products were submitted to an integrity study on in vitro model of the blood-brain-barrier (BBB) and the intestinal epithelium. No toxicity has been observed, suggesting that applications for the vectorization of active ingredients can be expected.

Straightforward extraction and selective bioconversion of high purity chitin from Bombyx eri larva: Toward an integrated insect biorefinery
Huet, G.; Hadad, C.; Husson, E.; Laclef, S.; Lambertyn, V.; Araya Farias, M.; Jamali, A.; Courty, M.; Alayoubi, R.; Gosselin, I.; Sarazin, C.; Van Nhien, A. N.
Carbohydr. Polym. 2020, 228, 115382.
Chitins of different purity grades (45%, 89.7% and 93.3%) were efficiently extracted from Bombyx eri larva and fully physico-chemically characterized. Compared to commercially available and extracted α-chitin from shrimp shell, the collected data showed that insect chitins had similar characteristics in terms of crystallographic structures (α-chitin), thermal stability and degree of acetylation (>87%). The major differences lay in the crystallinity indexes (66% vs 75% for shrimp chitin) and in the morphological structures. Furthermore, low ash contents were determined for the insect chitins (1.90% vs 21.73% for shrimp chitin), making this chitin extraction and purification easier, which is highly valuable for an industrial application. Indeed, after only one step (deproteinization), the obtained chitin from Bombyx eri showed higher purity grade than the one extracted from shrimp shells under the same conditions. Insect chitins were then subjected to room temperature ionic liquid (RTIL) pretreatment prior to enzymatic degradation and presented a higher enzymatic digestibility compared to commercial one whatever their purity grade and would be thus a more relevant source for the selective production of N-acetyl-D-glucosamine (899.2 mg/g of chitin-2 steps vs 760 mg/g of chitin com). Moreover, for the first time, the fermentescibility of chitin hydrolysates was demonstrated with Scheffersomyces stipitis used as ethanologenic microorganism.

New biobased-zwitterionic ionic liquids: efficiency and biocompatibility for the development of sustainable biorefinery processes
Huet, G.; Araya-Farias, M.; Alayoubi, R.; Laclef, S.; Bouvier, B.; Gosselin, I.; Cézard, C.; Roulard, R.; Courty, M.; Hadad, C.; Husson, E.; Sarazin, C.; Nguyen Van Nhien, A.
Green Chem. 2020, 22, 2935-2946.
A new family of biobased-zwitterionic ionic liquids (ZILs) have been synthesized starting from the renewable resource l-histidine natural amino acid and varying the lengths of the alkyl chains. These ZIL derivatives were firstly studied for their biocompatibility with different microorganisms including bacteria, molds and yeast. The obtained MIC values indicated that all the microorganisms were 5 to 25 times more tolerant to ZIL derivatives than the robust 1-ethyl-3-methylimidazolium acetate [C2mim][OAc] used as a reference. Modeling studies also revealed that the presence of the cation and the anion on the same skeleton together with the length of the N-alkyl chain would govern the biocompatibility of these neoteric solvents. Among the different synthesized ZILs, the N,N′-diethyl derivative has been demonstrated to be a suitable eco-alternative to the classically used [C2mim][OAc] for efficient pretreatment of harwood sawdust leading to a significant improvement of enzymatic saccharification. In addition, with up to a 5% w/v concentration in the culture medium, ZILs did not induce deleterious effects on fermentative yeast growth nor ethanol production.

Comparative binding and uptake of liposomes decorated with mannose oligosaccharides by cells expressing the mannose receptor or DC-SIGN
Gao, H.; Gonçalves, C.; Gallego, T.; François-Heude, M.; Malard, V.; Mateo, V.; Lemoine, F.; Cendret, V.; Djedaini-Pilard, F.; Moreau, V.; Pichon, C.; Midoux, P.
Carbohydr. Res. 2020, 487, 107877.
Mannose Receptor (MR) and DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) are two mannose-specific targets for antigens carried by liposomes but DC-SIGN is more specific of DCs. Here, DC targeting is addressed by using DPPC/DOPE liposomes decorated with a series of diether lipids with a polar head of either a mannose (Man), tri-antenna of α-d-mannopyranoside (Tri-Man), [Manα1-3(Manα1-6)Man] (Man-tri), pseudo-Man4 (PMan4) or pseudo-Man5 (PMan5). Liposomes decorated with Man-Tri show the highest binding and internalization in cells expressing DC-SIGN and in human monocytes-derived DCs. Conversely, cells expressing MR bind and take up Tri-Man liposomes 3-fold higher than Man-tri liposomes. Comparatively, liposomes decorated with PMan4 and PMan5 do not show any advantages. Overall, the results indicate that liposomes decorated with Man-tri residues are more selective toward DCs than those with Tri-Man thanks to better recognition by DC-SIGN.

Marine Natural Products with High Anticancer Activities
Dario, M.; Karlo, W.; Nela, M.; Sylvain, L.; Maris, T.; Maria, K.; Gabriela, A.; Dean, M.
Curr. Med. Chem. 2020, 27, 1-63.
This review covers recent literature from 2012-2019 concerning 170 marine natural products and their semisynthetic analogues with strong anticancer biological activities. Reports that shed light on cellular and molecular mechanisms and biological functions of these compounds, thus advancing the understanding in cancer biology are also included. Biosynthetic studies and total syntheses, which have provided access to derivatives and have contributed to the proper structure or stereochemistry elucidation or revision are mentioned. The natural compounds isolated from marine organisms are divided into nine groups, namely: alkaloids, sterols and steroids, glycosides, terpenes and terpenoids, macrolides, polypeptides, quinones, phenols and polyphenols, and miscellaneous products. An emphasis is placed on several drugs originating from marine natural products that have already been marketed or are currently in clinical trials.

Rhodium-Catalyzed Aqueous Biphasic Olefin Hydroformylation Promoted by Amphiphilic Cyclodextrins
Cocq, A.; Bricout, H.; Djedaïni-Pilard, F.; Tilloy, S.; Monflier, E.
Catalysts 2020, 10, 56.
Hydroformylation is an industrial process that allows for the production of aldehydes from alkenes using transition metals. The reaction can be carried out in water, and the catalyst may be recycled at the end of the reaction. The industrial application of rhodium-catalyzed aqueous hydroformylation has been demonstrated for smaller olefins (propene and butene). Unfortunately, larger olefins are weakly soluble in water, which results in very low catalytic activity. In an attempt to counteract this, we investigated the use of amphiphilic oleic succinyl-cyclodextrins (OS-CDs) synthesized from oleic acid derivatives and maleic anhydride. OS-CDs were found to increase the catalytic activity of rhodium during the hydroformylation of water-insoluble olefins, such as 1-decene and 1-hexadecene, by promoting mass transfer. Recyclability of the catalytic system was also evaluated in the presence of these cyclodextrins.

Production of Oligosaccharides from Agrofood Wastes
Cano, M. E.; García-Martin, A.; Comendador Morales, P.; Wojtusik, M.; Santos, V. E.; Kovensky, J.; Ladero, M.
Fermentation 2020, 6, 31.
The development of biorefinery processes to platform chemicals for most lignocellulosic substrates, results in side processes to intermediates such as oligosaccharides. Agrofood wastes are most amenable to produce such intermediates, in particular, cellooligo-saccharides (COS), pectooligosaccharides (POS), xylooligosaccharides (XOS) and other less abundant oligomers containing mannose, arabinose, galactose and several sugar acids. These compounds show a remarkable bioactivity as prebiotics, elicitors in plants, food complements, healthy coadyuvants in certain therapies and more. They are medium to high added-value compounds with an increasing impact in the pharmaceutical, nutraceutical, cosmetic and food industries. This review is focused on the main production processes: autohydrolysis, acid and basic catalysis and enzymatic saccharification. Autohydrolysis of food residues at 160–190 °C leads to oligomer yields in the 0.06–0.3 g/g dry solid range, while acid hydrolysis of pectin (80–120 °C) or cellulose (45–180 °C) yields up to 0.7 g/g dry polymer. Enzymatic hydrolysis at 40–50 °C of pure polysaccharides results in 0.06–0.35 g/g dry solid (DS), with values in the range 0.08–0.2 g/g DS for original food residues.

First Sustainable Aziridination of Olefins Using Recyclable Copper-Immobilized Magnetic Nanoparticles
Toumieux, S.; Khodadadi, M.; Pourceau, G.; Becuwe, M.; Wadouachi, A.
Synlett 2019, 30, 563-566.
The first copper-catalyzed aziridination of olefins using recyclable magnetic nanoparticles is described. Magnetic nanoparticles were modified with dopamine and used as a support to coordinate copper. The methodology was optimized with styrene as olefin and using [N-(p-toluenesulfonyl)imino]phenyliodinane (PhI=NTs) as nitrene source. A microwave irradiation decreased the reaction time by 4-fold compared to conventional heating method. The catalyst was recovered by simple magnetic extraction and could be reused successfully up to five times without significant loss of activity. The methodology was applied to a range of different olefins leading to moderate to excellent yields in the formation of the expected aziridine.

Unprecedented thiacalixarene fucoclusters strong inhibitors of Ebola cis-cell infection and HCMV-gB glycopro-tein/DC-SIGN C-type lectin interaction
Taouai, M.; Porkolab, V.; Chakroun, K.; Cheneau, C.; Luczkowiak, J.; Abidi, R.; Lesur, D.; Cragg, P. J.; Halary, F.; Delgado, R.; Fieschi, F.; Benazza, M.
Bioconjug Chem 2019, 30, 1114-1126.
Glycan-protein interactions control numerous biological events from cell-cell recognition and signaling to pathogen host cell attachment for infections. To infect cells, some viruses bind to immune cells thanks to DC-SIGN (dendritic cell [DC]-specific ICAM3-grabbing non-integrin) C-type lectin expressed on dendrit-ic and macrophage cell membrane, via their envelope protein. Prevention of this infectious interaction is a serious therapeutic option. Here, we describe the synthesis of first water-soluble tetravalent fucocluster pseudopeptide-based thiacalixarene 1,3-alternate as viral antigen mimics designed for the inhibition of DC-SIGN, to prevent viral particle uptake. Their preparation exploits straightforward convergent strate-gies involving one pot Ugi four-component (Ugi-4CR) and azido-alkyne click chemistry reactions as key steps. Surface plasmon resonance showed strong inhibition of DC-SIGN interaction properties by tetrava-lent ligands designed with high relative potencies and beta avidity factors. All ligands block DC-SIGN active sites at nanomolar IC50 preventing cis-cell infection by Ebola viral particles pseudotyped with EBOV gly-coprotein (Zaire species of Ebola virus) on Jurkat cells that express DC-SIGN. In addition, we observed strong inhibition of DC-SIGN/human cytomegalovirus (HCMV)-gB recombinant glycoprotein interaction. This finding opens the way to the simple development of new models of water-soluble glycocluster-based thiacalixarene with wide range antimicrobial activities.

Glycocluster Tetrahydroxamic Acids Exhibiting Unprecedented Inhibition of Pseudomonas aeruginosa Biofilms
Taouai, M.; Chakroun, K.; Sommer, R.; Michaud, G.; Giacalone, D.; Ben Maaouia, M. A.; Vallin-Butruille, A.; Mathiron, D.; Abidi, R.; Darbre, T.; Cragg, P. J.; Mullie, C.; Reymond, J. L.; O'Toole, G. A.; Benazza, M.
J. Med. Chem. 2019, 62, 7722-7738.
Opportunistic Gram-negative Pseudomonas aeruginosa uses adhesins (e.g., LecA and LecB lectins, type VI pili and flagella) and iron to invade host cells with the formation of a biofilm, a thick barrier that protects bacteria from drugs and host immune system. Hindering iron uptake and disrupting adhesins' function could be a relevant antipseudomonal strategy. To test this hypothesis, we designed an iron-chelating glycocluster incorporating a tetrahydroxamic acid and alpha-l-fucose bearing linker to interfere with both iron uptake and the glycan recognition process involving the LecB lectin. Iron depletion led to increased production of the siderophore pyoverdine by P. aeruginosa to counteract the loss of iron uptake, and strong biofilm inhibition was observed not only with the alpha-l-fucocluster (72%), but also with its alpha-d-manno (84%), and alpha-d-gluco (92%) counterparts used as negative controls. This unprecedented finding suggests that both LecB and biofilm inhibition are closely related to the presence of hydroxamic acid groups.

Ordering of Saturated and Unsaturated Lipid Membranes near Their Phase Transitions Induced by an Amphiphilic Cyclodextrin and Cholesterol
Roux, M.; Bonnet, V.; Djedaïni-Pilard, F.
Langmuir 2019.
When inserted in membranes of dimyristoyl phosphatidylcholine (DMPC), methylated β-cyclodextrins with one (TrimβMLC) or two (TrimβDLC) lauryl acyl chains grafted onto the hydrophilic cavity exert a “cholesterol-like ordering effect”, by straightening the acyl chains in the fluid phase at temperatures near the chain melting transition. This effect may be related to pretransitional events such as the “anomalous swelling” known to occur with saturated phosphatidylcholine membranes. To investigate this model, order profiles and bilayer thicknesses of DMPC and unsaturated 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) membranes containing amphiphilic cyclodextrins or cholesterol were determined by deuterium NMR. The pure lipid membranes display both a qualitatively similar chain ordering upon cooling in the fluid phase, more important at the chain extremity, which gets more pronounced near their fluid-to-gel transitions. Both membranes show a bilayer thickness increase by ∼0.5 Å just above their transition, as observed previously with saturated phosphatidylcholines of various chain lengths. Membrane-insertion of 5% TrimβMLC or cholesterol induces an important ordering of the DMPC acyl chains just above the transition, which is also more pronounced at the chain extremity. There is an additional increase of the bilayer thickness, most probably due to a deep insertion of these amphiphilic molecules, facilitated by increased bilayer softness in the anomalous swelling regime. These effects are more important with TrimβMLC than with cholesterol. By contrast, no enhanced acyl chain ordering was observed when approaching the transition of TrimβMLC-containing POPC membranes, as a possible consequence of an eventual lack of anomalous swelling in unsaturated lipid membranes. Insertion of higher concentrations of TrimβMLC was found to induce a magnetic orientation of the DMPC membranes in the fluid phase with 10% of this derivative, coupled with the appearance of a broad isotropic component when the concentration is raised to 20%. No membrane orientation or isotropic component was detected with TrimβMLC-containing POPC membranes.

Harnessing Polyisobutylene by Rotaxanation with γ-Cyclodextrin: Opportunities for Making Smart Molecular Necklaces
Przybylski, C.; Ramoul, H.; Bonnet, V.; Abad, M.; Jarroux, N.
Macromol. Chem. Phys. 2019, 220, 1800502.
Abstract A new type of polyrotaxane based on the threading of γ-cyclodextrins (γ-CDs) along a highly hydrophobic polymer, polyisobutylene (PIB), is successfully prepared and finely characterized. The used radical coupling associated with tuned reaction time and temperature leads to a fast and controlled necklace synthesis with low reagent consumption. Synthesis exhibits appealing conversion and threading rates with almost 100% and 62–73%, respectively. A combination of well-established SEC and NMR techniques, with a more forefront MALDI-TOF MS approach, provides details on the original PIB and the resulting polyrotaxanes (M w, M n, PDI, and average number of γ-CD threaded). Interestingly, tetramethylguanidinium-2-(4-hydroxyphenylazo)benzoate in DMF for MALDI analysis is revealed as a suitable matrix to overcome solubility troubles widely observed with PIB. Moreover, rotaxanation appears as an alternative to the grafting of polar groups to modify/handle hydrophobic polymers. Such an approach offers new opportunities to achieve the synthesis, with unambiguous evidence, of new supramolecular necklaces based on highly hydrophobic polymers.

A microscale double labelling of GAG oligosaccharides compatible with enzymatic treatment and mass spectrometry
Przybylski, C.; Bonnet, V.; Vivès, R. R.
Chem. Commun. (Cambridge, U. K.) 2019, 55, 4182-4185.
A novel double labelling of glycosaminoglycans (GAG) oligosaccharides by thia-Michael addition and deuterium incorporation at the non-reducing and reducing ends, respectively, was introduced. This was demonstrated to be both compatible with the heparin microgram scale and amenable for mass spectrometry analysis, without impairing enzymatic activities such as heparinase I and sulfatase HSulf-2.

Development Of C-Type Lectin Oriented Surfaces For High Avidity Glycoconjugates: Towards Mimicking Multivalent Interactions On The Cell Surface
Porkolab, V.; Pifferi, C.; Sutkeviciute, I.; Ordanini, S.; Taouai, M.; Thepaut, M.; Vivès, C.; Benazza, M.; Bernardi, A.; Renaudet, O.; Fieschi, F.
bioRxiv 2019, 780452.
Multivalent interactions between complex carbohydrates and oligomeric C-type lectins govern a wide range of immune responses. Up to date, standard SPR (surface plasmon resonance) competitive assays have largely been to evaluate binding properties from monosaccharide units (low affinity, mM) to multivalent elemental antagonists (moderate affinity, μM). Herein, we report typical case-studies of SPR competitive assays showing that they underestimate the potency of glycoclusters to inhibit the interaction between DC-SIGN and immobilized glycoconjugates. This paper describes the design and implementation of a SPR direct interaction over DC-SIGN oriented surfaces, extendable to other C-type lectin surfaces as such Langerin. This setup provides a microscopic overview of intrinsic avidity generation emanating simultaneously from multivalent glycoclusters and from DC-SIGN tetramers that are organized in nanoclusters on the cell membrane. For this purpose, covalent biospecific capture of DC-SIGN via StreptagII /StrepTactin interaction offers the preservation of tetrameric DC-SIGN and the accessibility/functionality of all active sites. From the tested glycoclusters libraries, we demonstrated that the scaffold architecture, the valency and the glycomimetic-based ligand are crucial to reach nanomolar affinities for DC-SIGN. The glycocluster 3.D illustrates the tightest binding partner in this set for a DC-SIGN surface (Kd= 18 nM). Moreover, the selectivity at monovalent scale of glycomimetic D can be easily analyzed at multivalent scale comparing its binding over different C-type lectin immobilized surfaces. This approach may give rise to novel insights into the multivalent binding mechanisms responsible to avidity and make a major contribution to the full characterization of the binding potency of promising specific and multivalent immunomodulators.

Nitroxide supported on nanometric metal oxides as new hybrid catalysts for selective sugar oxidation
Omri, M.; Becuwe, M.; Davoisne, C.; Pourceau, G.; Wadouachi, A.
J. Colloid Interface Sci. 2019, 536, 526-535.
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.

Nitroxide-Grafted Nanometric Metal Oxides for the Catalytic Oxidation of Sugar
Omri, M.; Becuwe, M.; Courty, M.; Pourceau, G.; Wadouachi, A.
ACS Applied Nano Materials 2019, 2, 5200-5205.
A new series of ([2,2,6,6-tetramethylpiperidin-1-yl]oxy) (TEMPO) catalysts supported on nanometric metal oxides (TiO2, AlO2, CeO2) and their efficiency for sugar oxidation are herein described. The preparation of such hybrid catalysts was carried out by modification of a metal oxide surface with a monolayer of phosphonic linker bearing a TEMPO radical. All prepared catalysts were carefully characterized by diffuse reflectance Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and transmission electron microscopy. The efficiency of these new hybrid TEMPO supported materials for sugar oxidation was evaluated on methyl α-d-glucoside, as a model carbohydrate. The three hybrid catalysts showed high selectivity, activity, and stability, suggesting a promising potential for rapidly obtaining acid sugar derivatives.

Solid-phase synthesis of molecularly imprinted polymer nanolabels: Affinity tools for cellular bioimaging of glycans
Medina Rangel, P. X.; Laclef, S.; Xu, J.; Panagiotopoulou, M.; Kovensky, J.; Tse Sum Bui, B.; Haupt, K.
Scientific Reports 2019, 9, 3923.
Hyaluronic acid (HA) is a glycosaminoglycan that plays many roles in health and disease and is a key biomarker of certain cancers. Therefore, its detection at an early stage, by histochemical methods, is of importance. However, intracellular HA can be masked by other HA-binding macromolecules, rendering its visualization somehow problematic. We show that fluorescent molecularly imprinted polymer nanogels (MIP-NPs), can localize and detect intracellular HA. MIP-NPs were synthesized by solid-phase synthesis on glass beads (GBs). GBs were functionalized with terminal alkyne groups on which an azide derivative of the template molecule glucuronic acid was immobilized via click chemistry. Immobilization via the anomeric carbon left the template’s carboxyl moiety free to enable strong stoichiometric electrostatic interactions with a benzamidine-based functional monomer, to confer selective recognition to the MIP-NPs. Due to the two-point orientation of the template, the resulting MIP-NPs were endowed with improved binding site homogeneity and specificity, reminiscent of monoclonal antibodies. These synthetic antibodies were then applied for probing and staining HA, of which glucuronic acid is a substructure (epitope), on human epidermal cells. Their excellent sensitivity, small size and water compatibility, enabled the MIP-NPs to visualize HA, as evidenced by confocal fluorescence micrographs.

High resolution MALDI-TOF-MS and MS/MS: Application for the structural characterization of sulfated oligosaccharides
Lesur, D.; Duhirwe, G.; Kovensky, J.
Eur. J. Mass Spectrom. 2019, 0, 428-436.
Sulfated oligosaccharides are involved in important biological events that are often modulated by specific sequences and sulfation patterns, but their structural analysis remains challenging. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) analysis of three different sulfated oligosaccharides (Fondaparinux, the octasulfated pentasaccharide, a disulfated heparin-derived tetrasaccharide 1, and an octasulfated maltoheptaose) 2 was performed using the 2-(4-hydroxyphenylazo)benzoic acid-tetramethylguanidinium (HABA-TMG2) matrix. High resolution mass spectrometry of the main ions observed was successful, and this was complemented by tandem mass spectrometry (MS/MS) analysis for structural assessment. Despite sulfate losses, fully sulfated molecular ions were observed and these allowed the determination of oligosaccharide structures: UA-GlcNAc-UA(2S)-AnhMan(6S) for compound 1 and (Glc6S)6-Glc (1S,6S) for compound 2.

Lactose derivatives as potential inhibitors of pectin methylesterases
L'Enfant, M.; Kutudila, P.; Rayon, C.; Domon, J.-M.; Shin, W.-H.; Kihara, D.; Wadouachi, A.; Pelloux, J.; Pourceau, G.; Pau-Roblot, C.
Int. J. Biol. Macromol. 2019, 132, 1140-1146.
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.

Synthesis of multivalent S-glycoside analogs of a heparan sulfate sequence
Koffi Teki, D. S.-E.; Bil, A.; Moreau, V.; Chagnault, V.; Fanté, B.; Adjou, A.; Kovensky, J.
Organic Chemistry Frontiers 2019, 6, 2718-2725.
Glycosaminoglycans (GAGs) are involved in the regulation of a large number of biological processes such as inflammation, cell signalling, angiogenesis, viral infection and coagulation. Unlike molecules isolated from tissues, pure molecules, derived from organic synthesis, can prevent side effects and are very useful tools for understanding the structure-activity relationships of many biological and pharmacological activities. In our research group, we focus particularly on the synthesis of multivalent thioglycoside analogs. In this article, we report the synthesis of new glycoclusters with thiodisaccharide units, S-analogs of heparan sulfate. The thiodisaccharide analog was obtained by nucleophilic displacement of a 4-triflate galactoside derivative, by an anomeric thiol of a glucuronic acid precursor. After modifying the aglycone part to introduce an azide, the thiodisaccharide was coupled to maltotriose scaffolds carrying one, two or three propargyl groups by CuAAC.

Tuning the Chemistry of Organonitrogen Compounds for Promoting All-Organic Anionic Rechargeable Batteries
Jouhara, A.; Quarez, E.; Dolhem, F.; Armand, M.; Dupré, N.; Poizot, P.
Angewandte Chemie International Edition 2019, 0.
Abstract The ever-increasing demand for rechargeable batteries induces significant pressure on the worldwide metal supply, depleting resources and increasing costs and environmental concerns. In this context, developing the chemistry of anion-inserting electrode organic materials could promote the fabrication of molecular (metal-free) rechargeable batteries. However, few examples have been reported because little effort has been made to develop such anionic-ion batteries. Here we show the design of two anionic host electrode materials based on the N-substituted salts of azaaromatics (zwitterions). A combination of NMR, EDS, FTIR spectroscopies coupled with thermal analyses and single-crystal XRD allowed a thorough structural and chemical characterization of the compounds. Thanks to a reversible electrochemical activity located at an average potential of 2.2 V vs. Li+/Li, the coupling with dilithium 2,5-(dianilino)terephthalate (Li2DAnT) as the positive electrode enabled the fabrication of the first all-organic anionic rechargeable batteries based on crystallized host electrode materials capable of delivering a specific capacity of ≈27 mAh/gelectrodes with a stable cycling over dozens of cycles (≈24 Wh/kgelectrodes).

Acidic Ionic Liquid as Both Solvent and Catalyst for Fast Chemical Esterification of Industrial Lignins: Performances and Regioselectivity
Husson, E.; Hulin, L.; Hadad, C.; Boughanmi, C.; Stevanovic, T.; Sarazin, C.
Frontiers in Chemistry 2019, 7.
Lignin can be considered an essential under-exploited polymer from lignocellulosic biomass representing a key for a profitable biorefinery. One method of lignin valorization could be the improvement of physico-chemical properties by esterification to enhance miscibility in apolar polyolefin matrices, thereby helping the production of bio-based composites. The present work describes for the first time a succeeded chemical esterification of industrial lignins with maleic anhydride in an acidic ionic liquid: 1-butyl-3-methyl imidazolium hydrogen sulfate without additional catalyst. This efficient strategy was applied to four industrial lignins: two softwood Kraft lignins (Indulin AT, Wayagamack), one hardwood Kraft lignin (Windsor), and one softwood organosolv lignin (Lignol), distinct in origin, extraction process and thus chemical structure. The chemical, structural, and thermal properties of modified lignins were characterized by 31P nuclear magnetic resonance, infrared spectroscopy and thermal analyses, then compared to those of unmodified lignins. After 4 h of reaction, between 30 to 52% of the constitutive hydroxyls were esterified depending on the type of lignin sample. The regioselectivity of the reaction was demonstrated to be preferentially orientated toward aliphatic hydroxyls for three out of four lignins (66.6, 65.5, and 83.6% for Indulin AT, Windsor and Lignol, respectively, vs. 51.7% for Wayagamack). The origin and the extraction process of the polymer would thus influence the efficiency and the regioselectivity of this reaction. Finally, we demonstrated that the covalent grafting of maleyl chain on lignins did not significantly affect thermal stability and increased significantly the solubility in polar and protic solvent probably due to additional exposed carboxylic groups resulted from mono-acylation independently of H/G/S ratio. Blending with polyolefins could then be considered in regard of compatibility with the obtained physico-chemical properties.

Conversion of Chitin in Ionic Liquids
Hadad, C.; Husson, E.; Van Nhien, A. N.
Encyclopedia of Ionic Liquids 2019, 1-6.
Present in the exoskeleton of arthropods or in the cell walls of fungi, chitin belongs to the most abundant polysaccharides after cellulose and is composed of linear chains of β-(1 → 4)- N-acetyl-D-glucosamine. There are three types of chitins (α-, β-, γ-chitin) with different crystallographic structures. Among them, α-chitin, the most prominent form, is arranged in an antiparallel fashion and is found in both crustacean and insects’ sources [ 21]. Despite its excellent biodegradability, biocompatibility, antimicrobial activity, nontoxicity, low immunogenicity, and good mechanical properties, chitin remains underutilized. This limitation in terms of application is mainly due to: (i) the low extraction efficiency, (ii) the extraction costs excessively high and not environmentally friendly, and (iii) the lack of solubility of this hydrophobic biopolymer. To overcome this weak solubility, pretreatments (chemical, mechanical, enzymatic, …) are interesting alternatives by...

Impact of the chemical structure on amphiphilic properties of sugar-based surfactants: A literature overview
Gaudin, T.; Lu, H.; Fayet, G.; Berthauld-Drelich, A.; Rotureau, P.; Pourceau, G.; Wadouachi, A.; Van Hecke, E.; Nesterenko, A.; Pezron, I.
Adv. Colloid Interface Sci. 2019, 270, 87-100.
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).

Synthesis of high molecular weight chitosan from chitin by mechanochemistry and aging
Di Nardo, T.; Hadad, C.; Nguyen Van Nhien, A.; Moores, A.
Green Chem. 2019, 21, 3276-3285.
Chitosan can be obtained from the deacetylation of chitin. This process is however difficult and usually accompanied by depolymerization, affording low molecular weight chitosan. We report a novel path, relying on the combination of mechanochemistry and aging, to yield high molecular weight chitosan with minimal use of energy and solvent. This method is versatile and applicable to a number of chitin sources, including crude crustacean and insect shells, yielding deacetylation up to 98% and remarkably high molecular weights. Chitin deacetylation was studied by magic angle spinning nuclear magnetic resonance and molecular weight was estimated by viscometry. This process affords chitosan in a safer fashion and with less materials and energy usage compared to the classic hydrothermal one.

Highly Water-Soluble Amphiphilic Cyclodextrins Bearing Branched and Cyclic Oleic Grafts
Cocq, A.; Rousseau, C.; Bricout, H.; Oliva, E.; Bonnet, V.; Djedaïni-Pilard, F.; Monflier, E.; Tilloy, S.
Eur. J. Org. Chem. 2019, 0, 4863-4868.
Amphiphilic β-cyclodextrins bearing various amounts of branched and cyclic oleic grafts are synthetized. The first step of this synthesis is the alkenylation of maleic anhydride by oleic acid derivatives, in the presence of a rhodium catalyst, to produce oleic succinic anhydrides with different ratios of cyclic to branched groups. The second step is the grafting of the oleic succinic anhydrides mixtures on β-cyclodextrin. The obtained cyclodextrins are highly water-soluble and surface active.

Oleic Acid Based Cyclodextrins for the Development of New Hydrosoluble Amphiphilic Compounds
Cocq, A.; Rousseau, C.; Bricout, H.; Oliva, E.; Bonnet, V.; Djedaïni-Pilard, F.; Monflier, E.; Tilloy, S.
Eur. J. Org. Chem. 2019, 2019, 1236-1241.
A new family of amphiphilic cyclodextrins produced from oleic acid derivatives and maleic anhydride is described. These amphiphilic cyclodextrins are synthesized in two steps. The first step is the alkenylation of maleic anhydride by oleic acid derivatives to produce the oleic succinic anhydrides. The second step is the grafting of the oleic succinic anhydrides on various cyclodextrins. A self-inclusion of the alkyl chain or an inclusion of one alkyl chain in the cavity of another CD is showed by NMR experiments. The twelve amphiphilic cyclodextrins described possess high solubility in water (50–500 g/L at 20 °C) and low critical aggregation concentration (16–360 mg/L).

Anionic Amphiphilic Cyclodextrins Bearing Oleic Grafts for the Stabilization of Ruthenium Nanoparticles Efficient in Aqueous Catalytic Hydrogenation
Cocq, A.; Léger, B.; Noël, S.; Bricout, H.; Djedaïni‐Pilard, F.; Tilloy, S.; Monflier, E.
ChemCatChem 2019, n/a.
Oleic succinyl β-cyclodextrin was proved to be efficient for the stabilization of ruthenium nanoparticles (NPs) in aqueous medium. These NPs were characterized by FTIR spectroscopy and transition electron microscopy (TEM). The catalytic activity of these NPs was evaluated in the aqueous hydrogenation of petrosourced and biosourced unsaturated compounds such as benzene and furfural derivatives. The catalytic system can be easily recycled and reused up to nine runs without any loss of activity and selectivity, demonstrating its robustness.

Ironing out pyoverdine’s chromophore structure: serendipity or design?
Cézard, C.; Sonnet, P.; Bouvier, B.
JBIC Journal of Biological Inorganic Chemistry 2019, 24, 659-673.
Pyoverdines are Pseudomonas aeruginosa’s primary siderophores. These molecules, composed of a fluorescent chromophore attached to a peptide chain of 6–14 amino acids, are synthesized by the bacterium to scavenge iron (essential to its survival and growth) from its environment. Hijacking the siderophore pathway to use pyoverdine–antibiotic compounds in a Trojan horse approach has shown promise but remains very challenging because of the synthetic efforts involved. Indeed, both possible approaches (grafting an antibiotic on pyoverdine harvested from Pseudomonas or designing a total synthesis route) are costly, time-consuming and low-yield tasks. Designing comparatively simple analogs featuring the salient properties of the original siderophore is thus crucial for the conception of novel antibiotics to fight bacterial resistance. In this work, we focus on the replacement of the pyoverdine chromophore, a major roadblock on the synthetic pathway. We propose three simpler analogs and evaluate their ability to complex iron and interact with the FpvA transporter using molecular modeling techniques. Based on these results, we discuss the role of the native chromophore’s main features (polycyclicity, positive charge, flexibility) on pyoverdine’s ability to bind iron and be recognized by membrane transporter FpvA and propose guidelines for the design of effective synthetic siderophores.

Curvature as a Collective Coordinate in Enhanced Sampling Membrane Simulations
Bouvier, B.
J. Chem. Theory Comput. 2019.
The plasticity of membranes plays an important functional role in cells, cell components, and micelles, where bending, budding, and remodeling implement numerous recognition and communication processes. Comparatively, molecular simulation methods to induce, control, and quantitatively characterize such deformations remain scarce. This work defines a novel collective coordinate associated with membrane bending, which strives to combine realism (by preserving the notion of local atomic curvatures) and low computational cost (allowing its evaluation at every time step of a molecular dynamics simulation). Enhanced sampling simulations along this conformational coordinate provide convenient access to the underlying bending free energy landscape. To showcase its potential, the method is applied to three state-of-the-art problems: the determination of the bending free energy landscape of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) bilayer, the formation of a POPE liposome, and the study of the influence of the Pseudomonas quinolone signal on the budding of Gram-negative bacterial outer membranes.

Effect of standard light illumination on electrolyte’s stability of lithium-ion batteries based on ethylene and di-methyl carbonates
Bouteau, G.; Van-Nhien, A. N.; Sliwa, M.; Sergent, N.; Lepretre, J.-C.; Gachot, G.; Sagaidak, I.; Sauvage, F.
Scientific Reports 2019, 9, 135.
Combining energy conversion and storage at a device and/or at a molecular level constitutes a new research field raising interest. This work aims at investigating how prolonged standard light exposure (A.M. 1.5G) interacts with conventional batteries electrolyte, commonly used in the photo-assisted or photo-rechargeable batteries, based on 1 mol.L−1 LiPF6 EC/DMC electrolyte. We demonstrate the intrinsic chemical robustness of this class of electrolyte in absence of any photo-electrodes. However, based on different steady-state and time-resolved spectroscopic techniques, it is for the first time highlighted that the solvation of lithium and hexafluorophosphate ions by the carbonates are modified by light exposure leading to absorbance and ionic conductivity modifications without detrimental effects onto the electrochemical properties.

Solvent- and catalyst-free transamidations of unprotected glycosyl carboxamides
Bensalah, F. O.; Bil, A.; Wittine, K.; Bellahouel, S.; Lesur, D.; Markovic, D.; Laclef, S.
Org. Biomol. Chem. 2019.
The transamidation reactions of unprotected mono- and disaccharidic carboxamides with various primary and secondary arylic, heterocyclic or aliphatic amines are described. This new method is green and atom efficient and gives good to high yields. Notably, the conditions do not require either a solvent or a catalyst and give ammonia as a single by-product. The described coupling reaction is compatible with a variety of functional groups and was used in the synthesis of various glycosidic derivatives and biologically relevant glycolipids. A plausible reaction mechanism involving an intermolecular H-bond activation of the starting carboxamides is proposed.

Synthesis and insecticidal activities of novel solanidine derivatives
Beaulieu, R.; Grand, E.; Stasik, I.; Attoumbre, J.; Chesnais, Q.; Gobert, V.; Ameline, A.; Giordanengo, P.; Kovensky, J.
Pest Manag Sci 2019, 75, 793-800.
BACKGROUND: Potato (Solanum tuberosum) is the fourth culture in the world and is widely used in the agri-food industries. They generate by-products in which alpha-chaconine and alpha-solanine, the two major solanidine-based glycoalkaloids of potato, are present. As secondary metabolites, they play an important role in the protection system of potato and are involved in plant protection against insects. To add value to these by-products, we described here new glycoalkaloids that could have phytosanitary properties. RESULTS: Solanidine, as a renewable source, was modified with an azido linker and coupled by copper-catalyzed alkyne azide cycloaddition to alkynyl derivatives of the monosaccharides found in the natural potato glycoalkakoids: D-glucose, D-galactose and L-rhamnose. The efficacy of our compounds was evaluated on the potato aphid Macrosiphum euphorbiae. The synthetic compounds have stronger aphicidal properties against nymphs than unmodified solanidine. They also showed strong aphicidal activities on adults and a negative impact on fecundity. CONCLUSION: Our synthetic neoglycoalkaloids affected Macrosiphum euphorbiae survival at the nymphal stage as well as at the adult stage. Furthermore, they induced a decrease in fecundity. Our results show that chemical modifications of by-products may afford new sustainable compounds for crop and plant protection. (c) 2018 Society of Chemical Industry.

Uncommon Strong Inhibition of α-Glucosidase by Multivalent Glycoclusters built on Cyclodextrins Scaffolds
Alali, U.; Vallin, A.; Bil, A.; Khanchouche, T.; Mathiron, D.; Przybylski, C.; Beaulieu, R. R.; Kovensky, J.; Benazza, M.; Bonnet, V.
Org. Biomol. Chem. 2019, 17, 7228-7237.
The homeostasis disruption of D-glucose causes diabetes, a dramatic world wide chronic disease. The type 1 diabetes is a succesfully treatable form, where the blood D-glucose is regulated by insulin treatement. In contrast the type 2 diabetes , the non Insulin dependent one, is problematic. The control of the D-glucose blood level via intestinal α-D-glucosidase inactivation can be achieved by using competitive inhibitors as iminosugars (e.g. acarbose) or sulfonium sugar derivatives (e.g. salacinol). Recently, an unprecedented result showed that multivalent diamond nanoparticules grafted with unmodified sugars displayed α-glucosidase inhibition at low micromolar concentrations. We describe herein the synthesis of multivalent glycoclusters using cyclodextrines (CDs) as scaffolds and their assessment as inhibithors of α-D-glucosidase. The glycoclusters were efficiently obtained from per-azido α, β and γ-CDs derivatives and propargyl glycosides using click-chemistry under microwave irradiation. The methodology was successfully applied to various protected and non-protected propargylated monosaccharides, including both O- and S- glycosides, giving clear evidences of its versatility. The targeted 6-per-glycosylated CDs were isolated in moderate to excellent yields (30-90 %) by silica gel chromatography. The results showed inhibition of α-glucosidase from Saccharomyces cerevisiae with IC50 values in a 32-132 µM range, lower than that of acarbose (IC50 ~250µM), a well knowm competitive inhibitor used in clinical treatment of type 2 diabetes. Preliminary experiments suggest a mixed-type non-competitive inhibition mode of these new glycoclusters.

Biological impact of octyl D-glucopyranoside based surfactants
Zdarta, A.; Pacholak, A.; Smułek, W.; Zgoła-Grześkowiak, A.; Ferlin, N.; Bil, A.; Kovensky, J.; Grand, E.; Kaczorek, E.
Chemosphere 2018, 217, 567-575.
Development of many branches of industry has stimulated the search for new, effective surfactants with interesting properties. Potential use of alkyl glucose derivatives on a large scale, raises questions about the possible risks associated with their entry into the natural environment. To be able to evaluate this risk, the aim of the study was to determine the physicochemical properties of octyl D-glucopyranoside and its three derivatives: N-(octyl D-glucopyranosiduronyl)aspartic acid, N-(octyl D-glucopyranosiduronyl)glicyne and octyl D-glucopyranosiduronic acid. Moreover, their biodegradability by pure bacterial strains and biocenosis present in river water was examined. While descriptions of sugar-based surfactants on microbial cells are limited, the essential element of the study was to determine the effect of surfactants on cell surface properties of microorganisms isolated from activated sludge and compare it to the effects of the petroleum based surfactants and the surfactants produced from renewable materials. The results obtained indicate that physicochemical properties of surface active agents differ depending on the presence of functional groups in the surfactants molecules. What is more, the presence of amino acid substituent in the derivatives of octyl D-glucopyranoside resulted in a slight decrease in the surfactants biodegradation efficiency, in comparison to the compounds that did not contain such a substituent, prolonging this process from 5 to 10 days. Interestingly, even relatively slightly different derivatives modified the cell surface properties in a different way. Importantly, the surfactants based on octyl D-glucopyranoside have less negative impact on environmental microorganism and better biodegradability than the surfactant synthesized from petroleum products.

New iodide-based amino acid molecules for more sustainable electrolytes in dye-sensitized solar cells
Sagaidak, I.; Huertas, G.; Nguyen Van Nhien, A.; Sauvage, F.
Green Chem. 2018, 20, 1059-1064.
The electrolyte is the second key component governing at once power conversion performances and stability of dye-sensitized solar cells. Towards the integration of more sustainable materials, we focused in the replacement of the major constituent of the electrolyte, namely the 1,3 di-alkyl imidazolium iodide. We synthesized two new iodide molecules derived from natural amino acid family (L-proline): (S)-2-(methoxycarbonyl)-1,1-dimethylpyrrolidinium iodide (PMeI) and (S)-2-(ethoxycarbonyl)-1,1-ethylpyrrolidinium iodide (PEtI). In combination with the C106 polypyridyl ruthenium(+II) sensitizer, power conversion efficiencies of 7.1% for PMeI and 6.5% for PEtI were obtained under standard Air Mass 1.5G conditions in conjunction with low-volatile 3-methoxypropionitrile-based solvent. The relationship between these new iodide molecules, the power conversion efficiency and interfacial charge transfer processes is herein discussed and systematically compared to the best standard 1,3 di-methylimidazolium iodide.

Revealing cooperative binding of polycationic cyclodextrins with DNA oligomers by capillary electrophoresis coupled to mass spectrometry
Przybylski, C.; Benito, J. M.; Bonnet, V.; Mellet, C. O.; García Fernández, J. M.
Anal. Chim. Acta 2018, 1002, 70-81.
Gene delivery is critical for the development of nucleic acid-based therapies against a range of severe diseases. The conception of non-viral (semi)synthetic vectors with low cytotoxicity and virus-like efficiency is gathering a lot of efforts, but it represents a fantastic challenge still far from accomplishment. Carbohydrate-based scaffolds offer interesting features towards this end, such as easy availability, relatively cheap cost, tuning properties and a good biocompatibility. The lack of analytical methods providing quantitative and qualitative data on their binding properties with oligonucleotides (DNA/RNA), with a minimal time and sample consumption, represents a limitation for these channels. Here, we attempted to fill the gap by hyphenation of capillary electrophoresis with mass spectrometry (CE-MS). This coupling strategy allows discriminating free and complexed DNA oligomers with cationic cyclodextrins (CDs), determining the stoichiometry where the highest observed is always DNAn: n/3(CD), and unambiguously assigning the partners through m/z detection. Very reliable data were obtained with migration time within 5.5 (standard deviation < 0.5%) and 25 min (standard deviation < 1.1%) for UV and MS detection, respectively. Furthermore, varying the nitrogen/phosphorus ratio (N/P), key parameters relating to the thermodynamics e.g. the micro and macroscopic dissociation constants Kd and KD, respectively (both in low μM range) and the Gibbs free energy ΔG (−16.3 to −26.9 kJ mol−1), and also the cooperativity as Hill number (nH between 0.98 and 15.75) of the supramolecular process can be delineated, providing a unique tool for the high throughput screening and selection of efficient gene delivery carriers.

Preparation of nucleoside derivative carrying an isothiazole or oxathiole cycle with an antiproliferative activity
Postel, D.; Marolleau, J.-P.; Josse, S.; Nguyen Van Nhien, A.; Chagnault, V.; Marcq, I.; Bouhlal, H.
Patent 2018, WO2018109416A1.
Nucleoside deriv. carrying an isothiazole or oxathiole cycle I, wherein A is dioxo-isothiazole or dioxo-oxathiole spiro-furan derivs; R is oxygen; R1 is alkyl, alkenyl, alkynyl, hetero-aryl; R2 is H, halogen, alkyl, alkenyl, alkynyl, aryl, hetero-aryl, aryl, were prepd. as antitumor agents with antiproliferative activity. Thus, nucleoside II was prepd. and tested in vitro as antitumor agent (EC50 = 15 μM). [on SciFinder(R)]

Photocatalyzed Transformation of Free Carbohydrates
Omri, M.; Sauvage, F.; Golonu, S.; Wadouachi, A.; Pourceau, G.
Catalysts 2018, 8, 672.
In the growing context of sustainable chemistry, one of the challenges of organic chemists is to develop efficient and environmentally friendly methods for the synthesis of high-added-value products. Heterogeneous photocatalytic transformations have brought revolution in this regard, as they take advantage of an unlimited source of energy (solar light) or artificial UV light to onset organic chemical modifications. The abundance of free carbohydrates as chemical platform feedstock offers a great opportunity to obtain a variety of industrial interest compounds from biomass. Due to their chirality and polyfunctionality, the conversion of sugars generally requires multi-step protocols with protection/deprotection steps and hazardous chemical needs. In this context, several selective and eco-friendly methodologies are currently under development. This review presents a state of art of the recent accomplishments concerning the use of photocatalysts for the transformation and valorization of free carbohydrates. It discusses the approaches leading to the selective oxidation of free sugars, their degradation into organic chemicals, or their use for hydrogen production.

Gold Catalysis and Photoactivation: A Fast and Selective Procedure for the Oxidation of Free Sugars
Omri, M.; Sauvage, F.; Busby, Y.; Becuwe, M.; Pourceau, G.; Wadouachi, A.
ACS Catalysis 2018, 1635-1639.
A fast and efficient methodology for the selective oxidation of sugars into corresponding sodium aldonates is herein reported. Hydrogen peroxide was used as a cheap oxidant and electron scavenger, in the presence of only 0.003-0.006 mol % of gold in basic conditions. Three photocatalysts were studied, namely Au/Al2O3, Au/TiO2 and Au/CeO2, the latter being the most efficient (TOF > 750 000 h-1) and perfectly selective. Only 10 minutes exposition under standard incident sunlight irradiation (A.M.1.5G conditions - 100 mW/cm2) affords total conversion of glucose into the corresponding sodium gluconate. Demonstrating its versatility, this methodology was successfully applied to a variety of oligosaccharides leading to the corresponding aldonates in quantitative yield and high purity (>95%) without any purification step. The photocatalyst was recovered by simple filtration and re-used 5 times leading to the same conversion and selectivity after 10 min of illumination.

Physico-chemical studies of resveratrol, methyl-jasmonate and cyclodextrin interactions: an approach to resveratrol bioproduction optimization
Oliva, E.; Mathiron, D.; Bertaut, E.; Landy, D.; Cailleu, D.; Pilard, S.; Clément, C.; Courot, E.; Bonnet, V.; Djedaïni-Pilard, F.
RSC Advances 2018, 8, 1528-1538.
trans-Resveratrol (RSV) is a natural phenolic molecule of the stilbene family known for its anti-oxidant properties in the field of nutraceuticals and cosmetics. Its production by grapevine cell suspensions is induced by the addition to the culture medium of elicitor compounds, methyl jasmonate (MeJA) and cyclodextrins (CDs). Physico-chemical studies were performed to understand the mechanism of action of CDs on this bioproduction of RSV. Inclusion complexes of RSV in CDs were first observed and then interactions with MeJA were identified using various analytical techniques such as UV and nuclear magnetic resonance (NMR) spectroscopies, mass spectrometry (MS) and isothermal titration calorimetry (ITC).

Investigation of the stability of metal borohydrides-based compounds LiM(BH4)3Cl (M=La, Ce, Gd) as solid electrolytes for Li-S batteries
Nguyen, J.; Fleutot, B.; Janot, R.
Solid State Ionics 2018, 315, 26-32.
The LiM(BH4)3Cl (M=La, Ce, Gd) compounds are prepared by ball-milling followed by annealing and their electrochemical stabilities are investigated. To validate the use of these compounds as solid-state electrolytes, their stabilities versus Li and Li-In alloy are tested in symmetrical cells and their electrochemical stability windows are studied by cyclic voltammetry. We show that LiCe(BH4)3Cl is the more stable phase without any formation of a resistive layer upon cycling. All-solid-state Li-S batteries using a carbon‑sulfur composite as the positive electrode material are then assembled using LiCe(BH4)3Cl as the electrolyte. Reversible electrochemical reaction between Li and sulfur takes place at 45°C with an initial discharge capacity of 1186mAh/g of S under a current density of 13μA/cm2 (i.e. a rate of charge/discharge of C/100). The capacity retention is significant with still a value of 510mAh/g after 9cycles showing for the first time the possible use of LiCe(BH4)3Cl as solid electrolyte of Li-S batteries.

Synthesis of phosphorus analogs of TSAO-T
Moura, M.; Josse, S.; Postel, D.
Tetrahedron 2018, 74, 4721-4727.
Phosphorus Analogs of TSAO bearing an oxaphospholene ring instead of an oxathiole dioxide ring at C-3′ position were prepared. Strategy developed previously on saccharidic moiety was used with introduction of an electron withdrawing α group neighboring the phosphorus atom. Biological evaluation on both HIV-1 and HCV showed that these compounds have no activity.

An air-stable lithiated cathode material based on a 1,4-benzenedisulfonate backbone for organic Li-ion batteries
Lakraychi, A. E.; Deunf, E.; Fahsi, K.; Jimenez, P.; Bonnet, J. P.; Djedaini-Pilard, F.; Bécuwe, M.; Poizot, P.; Dolhem, F.
Journal of Materials Chemistry A 2018, 6, 19182-19189.
To meet current market demands as well as emerging environmental concerns there is a need to develop less polluting battery technologies. Organic electrode materials could offer the possibility of preparing electrode materials from naturally more abundant elements and eco-friendly processes coupled with simplified recycling management. However, the potential use of organic electrode materials for energy storage is still challenging and a lot of developments remain to be achieved. For instance, promoting high-energy Li-ion organic batteries inevitably requires the development of lithiated organic electrode materials which are able to be charged (delithiated) at a high enough potential (>3 V vs. Li+/Li0) – a challenging point rarely discussed in the literature. Here, we evaluate tetralithium 2,5-dihydroxy-1,4-benzenedisulfonate as an air-stable lithiated cathode material for the first time and its reversible Li+ electrochemical extraction. Quite interestingly, in comparison with the dicarboxylate counterpart, it was observed that the theoretical two-electron reaction is readily reached with this organic structure and at an average operating potential of 650 mV higher.

Du magnésium pour booster les batteries au lithium
Jouhara, A.; Dupre, N.; Gaillot, A. C.; Guyomard, D.; Dolhem, F.; Poizot, P.
Communiqué de presse 2018.
De plus en plus utilisées par les nouvelles technologies (smartphones, tablettes, …), les batteries « Li-ion » s’avèrent aussi de plus en plus gourmandes en ressources pour fonctionner. Une solution consiste au développement de batteries Li-ion organiques, plus vertes. Des chercheurs nantais de l’Institut des Matériaux Jean Rouxel (IMN, Université de Nantes/CNRS) et du Laboratoire de Glycochimie, des Antimicrobiens et des Agroressources (LG2A, Université de Picardie Jules Verne/CNRS) ont découvert un moyen inédit d’augmenter l’énergie de ces batteries Li-ion organiques grâce à l’ajout de magnésium. Ces résultats, publiés dans Nature Communications, pourraient permettre le développement de nouvelles batteries à faible impact environnemental et plus compétitive par rapport aux batteries Li-ion actuelles.

Raising the redox potential in carboxyphenolate-based positive organic materials via cation substitution
Jouhara, A.; Dupre, N.; Gaillot, A. C.; Guyomard, D.; Dolhem, F.; Poizot, P.
Nat Commun 2018, 9, 4401.
Meeting the ever-growing demand for electrical storage devices requires both superior and "greener" battery technologies. Nearly 40 years after the discovery of conductive polymers, long cycling stability in lithium organic batteries has now been achieved. However, the synthesis of high-voltage lithiated organic cathode materials is rather challenging, so very few examples of all-organic lithium-ion cells currently exist. Herein, we present an inventive chemical approach leading to a significant increase of the redox potential of lithiated organic electrode materials. This is achieved by tuning the electronic effects in the redox-active organic skeleton thanks to the permanent presence of a spectator cation in the host structure exhibiting a high ionic potential (or electronegativity). Thus, substituting magnesium (2,5-dilithium-oxy)-terephthalate for lithium (2,5-dilithium-oxy)-terephthalate enables a voltage gain of nearly +800 mV. This compound being also able to act as negative electrode via the carboxylate functional groups, an all-organic symmetric lithium-ion cell exhibiting an output voltage of 2.5 V is demonstrated.

Nanoparticles based on lipidyl-β-cyclodextrins: synthesis, characterization, and experimental and computational biophysical studies for encapsulation of atazanavir
Furlan, A. L.; Buchoux, S.; Miao, Y.; Banchet, V.; Létévé, M.; Lambertyn, V.; Michel, J.; Sarazin, C.; Bonnet, V.
New J. Chem. 2018, 42, 20171-20179.
Amphiphilic cyclodextrins were synthesized from permethylated βCD with the aim of forming nanoparticles (NPs) that would encapsulate specific molecules (e.g. drugs) which could enhance their otherwise poor bioavailability. By grafting different fatty acids, four amphiphilic CDs were obtained. The self-assembling properties of three of these compounds were evaluated demonstrating micromolar critical aggregation concentration (CAC). Additionally, the stability of these nanoparticles was studied revealing that the compounds with C18 chains could be stored at 4 °C for prolonged periods without any issue. Finally, reliable characterization of NPs made of di-oleoyl-glycerolipidyl-β-cyclodextrin (DOCD) was performed by combining DLS, cryo-transmission electron microscopy (cryo-TEM) and molecular dynamics (MD) simulations. This revealed that DOCD nano-assemblies are roughly nano-scaled, spherical objects (diameter ca. 120 nm) without internal organization or aqueous compartments. Finally, atazanavir, used as a model drug, was entrapped in NPs whilst MD simulations were used to investigate molecule entrapment. This revealed that atazanavir interacts with DOCD to form a drug-loaded NP which does not fit with the 2 : 1 stoichiometry encapsulation classically observed in the cyclodextrin cav

Water-mediated synthesis of disubstituted 5-aminopyrimidines from vinyl azides under microwave irradiation
Dehbi, O.; Ishak, E. A.; Bakht, M. A.; Geesi, M. H.; Alshammari, M. B.; Chagnault, V.; Kaiba, A.; Lazar, S.; Riadi, Y.
Green Chemistry Letters and Reviews 2018, 11, 62-66.
An efficient and ecofriendly method for the synthesis of disubstituted 5-aminopyrimidines from vinyl azides and urea or thiourea was developed. This reaction proceeds under microwave irradiation conditions in the presence of water as a solvent. The remarkable features of this new protocol are high conversion, short reaction times, cleaner reaction profiles and straightforward procedure.

The influence of chloride and hydrogen sulfate anions in two polymerised ionic liquids based on the poly(1-(hydroxyethyl)-3-vinylimidazolium cation, synthesis, thermal and vibrational studies
Chaker, Y.; Debdab, M.; Belarbi, E. H.; Ilikti, H.; Haddad, B.; Moumene, T.; Wadouachi, A.; Van Nhien, A. N.; Abassi, H. B.; Abbas, O.; Bresson, S.
Eur. Polym. J. 2018, 108, 138-149.
The chemical reaction of 2-chloroethanol with 1-vinylimidazol as precursor led to the corresponding compound 1-hydroxyethyl-3-vinylimidazolium chloride [EtOHVIM+] [Cl−]. In the next step, treatment of [EtOHVIM+][Cl−] with 2,2-azobisisobutyronitril (AIBN) afforded the poly1-(hydroxyethyl)-3-vinylimidazolium chloride (poly[EtOHVIM+][Cl−]), Finally, the reaction of (poly[EtOHVIM+][Cl−]) and sulfuric acid led to poly 1-(hydroxyethyl)-3-vinylimidazolium hydrogen sulfate (poly[EtOHVIM+][HSO4−]) by replacing the [Cl−] halide by an [HSO4−] anion. The structure of these compounds was identified by 1H NMR, 13C NMR as preliminary spectroscopic characterization. To obtain information on the structure and vibrational behavior in these compounds, vibrational spectroscopy measurements were investigated by Fourier Transform-Infrared-Attenuated Total Reflectance and Fourier Transform Raman spectroscopy in the spectral range 600–4000 cm−1 and 4000–500 cm−1, respectively. The Polymerization of IL gave rise to specific marks in the Raman and IR spectra and enhanced its vibrational property. Also, in order to understand the thermal stability in these compounds, the results concerning the melting point, glass transition and decomposition were determined by thermogravimetric analysis (TGA), differential thermal (DTG), and differential scanning calorimetry (DSC). The results indicated that the poly [EtOHVIM+][HSO4−] compound showed interesting thermal properties like high temperature of degradation and low temperature of glass transition compared to poly[EtOHVIM+][Cl−].

Metal-free oxidative esterification of benzylated monosaccharides
Camara, T.; Bil, A.; Chagnault, V.
Carbohydr. Res. 2018, 462, 45-49.
Methyl glyconates have been attracting considerable attention as intermediates for the preparation of aryl C-glycosides, polyphenolic products, aliphatic polyesters, SGLT2 inhibitors, antibiotics etc ... In view of the interest in those compounds, we report herein our work on the synthesis of methyl glyconates using an oxidative esterification carried out by molecular iodine. This reaction is catalyzed by non-toxic K4Fe(CN)6 that releases a small amount of cyanide ion into the reaction mixture. Four benzylated carbohydrates which contain a hemiacetalic functional group have been tested successfully.

XRD and ATR/FTIR investigations of various montmorillonite clays modified by monocationic and dicationic imidazolium ionic liquids
Ahmed, A.; Chaker, Y.; Belarbi, E. H.; Abbas, O.; Chotard, J. N.; Abassi, H. B.; Van Nhien, A. N.; El Hadri, M.; Bresson, S.
J. Mol. Struct. 2018, 1173, 653-664.
Three different montmorillonites (Mts) labeled K10, KSF and SWy-3 were analyzed by X-ray diffraction and ATR/FTIR spectroscopy. The XRD results enabled validation of the purification process of the studied clays. In the spectral regions 3800–2600 and 1800-1300 cm-1, the study of different intensity ratios of peaks assigned to the OH bending and stretching modes displayed the specific vibrational behavior of SWy-3 which is certainly influenced by a greater proportion of Na+ in its structure. Before analyzing the clays modified by ionic liquids, we characterized two imidazolium based ionic liquids (ILs) with anion I-: [EMIM+] [I−] monocationic ionic liquid and [M(CH₂) IM2+] [2I−] dicationic ionic liquid. The passage from [EMIM+] [I−] to [M(CH₂) IM2+] [2I−] reveals significant vibrational changes through various modes: ν(NH), rings ν(CC), rings ν(CN), ν(CH2(N)), ν(CH3(N)) in addition to anion interaction modes. When purified, these ionic liquids modify clays, the XRD analysis shows that the studied modified clays exhibited higher d-value increase with respect to the purified Mts, and the reflection peaks 2θ (°) of plane (001) were displaced towards lower values as a consequence of the ionic liquid intercalation process. ATR/FTIR spectra recorded in the spectral zone 4000-600 cm-1 indicated the appearance of new peaks and a significant intensity variation between clays in relation to the type of chosen ionic liquid. These vibrational changes are directly connected to the presence of ionic liquids in clays. XRD and ATR/FTIR investigations show a stronger effect of the [M(CH2) IM2+] [2I−] dicationic ionic liquid on the Mts than the monocationic ionic liquid and the SWy-3 Mt is more sensitive to monocationic and dicationic ionic liquids than K10 and KSF Mts.

La chimie en Région Hauts-de-France : Chimie, biologie et santé
Stéphane Lebrun, V. A., Philippe Amouyel, Christophe Biot, Véronique Bonnet, Benoit Deprez, Pierre André Gilormini, Cédric Lion, Oleg Melnyk, Patricia Melnyk et Jérôme Vicogne
Actualité Chimique 2017, 46-51.
Cet article présente un tour d’horizon de quelques-unes des thématiques de recherche développées en région Hauts-de-France dans les domaines de la chimie, de la biologie et de la santé.

Kinetics of the incorporation of the main phenolic compounds into the lignan macromolecule during flaxseed development
Ramsay, A.; Fliniaux, O.; Quero, A.; Molinie, R.; Demailly, H.; Hano, C.; Paetz, C.; Roscher, A.; Grand, E.; Kovensky, J.; Schneider, B.; Mesnard, F.
Food Chem. 2017, 217, 1-8.
The main flax lignan, secoisolariciresinol diglucoside, is stored in a macromolecule containing other ester-bound phenolic compounds. In this study, NMR and HPLC-UV analyses were performed on flaxseeds harvested at different developmental stages to identify and quantify the main phenolic compounds produced during seed development. Extraction was carried out with or without alkaline hydrolysis to determine if these molecules accumulate in the lignan macromolecule and/or in a free form. Monolignol glucosides accumulate in a free form up to 9.85mg/g dry matter at the early developmental stages. Hydroxycinnamic acid glucosides and flavonoid accumulate (up to 3.18 and 4.07mg/g dry matter, respectively) in the later developmental stages and are ester-bound in the lignan macromolecule. Secosiolariciresinol diglucoside accumulates (up to 28.65mg/g dry matter) in the later developmental stages in both forms, mainly ester-bound in the lignan macromolecule and slightly in a free form.

La chimie en Région Hauts-de-France : Chimie de la biomasse
Philippe Zinck, J.-M. A., Rémi Beaulieu, Fanny Bonnet, Thierry Delaunay, Franck Dumeignil, Cédric Epoune Lingome, Audrey Favrelle, Régis Gauvin, Frédéric Hapiot, Nicolas Jacquel, José Kovensky, Raphaël Lebeuf, Christophe Len, Éric Monflier, Véronique Nardello-Rataj, Jesus F. Ontiveros, Sébastien Paul, René Saint-Loup, Mathieu Sauthier, Isabelle Suisse, Marc Visseaux, Anne Wadouachi et Patrice Woisel
Actualité Chimique 2017, 40-45.
Cet article présente un tour d’horizon de quelques-unes des thématiques de recherche développées en région Hauts-de-France dans les domaines de la chimie de la biomasse.

Phenylpropanoid profiling reveals a class of hydroxycinnamoyl glucaric acid conjugates in Isatis tinctoria leaves
Nguyen, T. K.; Jamali, A.; Grand, E.; Morreel, K.; Marcelo, P.; Gontier, E.; Dauwe, R.
Phytochemistry 2017, 144, 127-140.
The brassicaceous herb, Isatis tinctoria, is an ancient medicinal plant whose rosette leaf extracts have anti-inflammatory and anti-allergic activity. Brassicaceae are known to accumulate a variety of phenylpropanoids in their rosette leaves acting as antioxidants and a UV-B shield, and these compounds often have pharmacological potential. Nevertheless, knowledge about the phenylpropanoid content of I. tinctoria leaves remains limited to the characterization of a number of flavonoids. In this research, we profiled the methanol extracts of I. tinctoria fresh leaf extracts by liquid chromatography - mass spectrometry (LC-MS) and focused on the phenylpropanoid derivatives. We report the structural characterization of 99 compounds including 18 flavonoids, 21 mono- or oligolignols, 2 benzenoids, and a wide spectrum of 58 hydroxycinnamic acid esters. Besides the sinapate esters of malate, glucose and gentiobiose, which are typical of brassicaceous plants, these conjugates comprised a large variety of glucaric acid esters that have not previously been reported in plants. Feeding with (13)C6-glucaric acid showed that glucaric acid is an acyl acceptor of an as yet unknown acyltransferase activity in I. tinctoria rosette leaves. The large amount of hydroxycinnamic acid derivatives changes radically our view of the woad metabolite profile and potentially contributes to the pharmacological activity of I. tinctoria leaf extracts.

Measurement of cytotoxicity and irritancy potential of sugar-based surfactants on skin-related 3D models
Lu, B.; Miao, Y.; Vigneron, P.; Chagnault, V.; Grand, E.; Wadouachi, A.; Postel, D.; Pezron, I.; Egles, C.; Vayssade, M.
Toxicol. in Vitro 2017, 40, 305-312.
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.

Carboxylic and sulfonic N-substituted naphthalene diimide salts as highly stable non-polymeric organic electrodes for lithium batteries
Lakraychi, A. E.; Fahsi, K.; Aymard, L.; Poizot, P.; Dolhem, F.; Bonnet, J. P.
Electrochem. Commun. 2017, 76, 47-50.
Two N-substituted naphthalene tetracarboxylic diimide (NTCDI) ionic compounds, carboxylic and sulfonic sodium salts, were prepared and used as positive electrode active materials in lithium-half cells. The aim of this investigation was to assess the solubility-suppressing effect of two different negatively charged substituent groups on a redox-active organic backbone using a carbonate-based liquid electrolyte. NTCDI derivatives were obtained in high yields from reaction of naphthalene tetracarboxylic dianhydride with neutralized glycine or with neutralized taurine. They were mixed with carbon black and cycled in galvanostatic mode against lithium metal using 1 M LiPF6 EC/DMC liquid electrolyte. These two NTCDI derivatives exhibit a quite stable electrochemical activity upon cycling at an average potential of 2.3 V vs. Li+/Li0 giving rise to specific capacity values of 147 mAh•g− 1 and 113 mAh•g− 1 for the dicarboxylate and the disulfonate derivative, respectively. This study clearly supports the useful effect of such grafted permanent charges as a general rule on the electrochemical stability of crystallized organic materials based on the assembly of small redox-active units.

Decreasing redox voltage of terephthalate-based electrode material for Li-ion battery using substituent effect
Lakraychi, A. E.; Dolhem, F.; Djedaïni-Pilard, F.; Thiam, A.; Frayret, C.; Becuwe, M.
J. Power Sources 2017, 359, 198-204.
The preparation and assessment versus lithium of a functionalized terephthalate-based as a potential new negative electrode material for Li-ion battery is presented. Inspired from molecular modelling, a decrease in redox potential is achieved through the symmetrical adjunction of electron-donating fragments (–CH3) on the aromatic ring. While the electrochemical activity of this organic material was maximized when used as nanocomposite and without any binder, the potential is furthermore lowered by 110 mV upon functionalization, consistently with predicted value gained from DFT calculations.

Applications of Glycosaminoglycans in the Medical, Veterinary, Pharmaceutical, and Cosmetic Fields
Kovensky, J.; Grand, E.; Uhrig, M. L.
Industrial Applications of Renewable Biomass Products: Past, Present and Future 2017, 135-164.
Glycosaminoglycans (GAGs) are complex polysaccharides ubiquitously present in the extracellular matrix of mammalian tissues, where they constitute the gelatinous material responsible for maintaining the cells together, in an intimate association with a variety of proteins. Although their structures are not strictly regular, they are composed of a repeating unit of a hexosamine-containing disaccharide. Most of them possess uronic acid residues, and with the exception of hyaluronic acid, they also carry sulfate groups. As a consequence of their high negative charge, they have an extraordinary capacity to absorb water. GAGs participate in many relevant biological processes by interaction with a plethora of proteins, and thus, a large number of applications in different fields have been conceived for GAGs and their derivatives.

Anti-mycotoxin Effect and Antifungal Properties of Essential Oil from Ammodaucus leucotrichus Coss. & Dur. on Aspergillus flavus and Aspergillus ochraceus
Khaldi, A.; Meddah, B.; Moussaoui, A.; Sonnet, P.
Journal of Essential Oil Bearing Plants 2017, 20, 36-44.
AbstractThe essential oil of Ammodaucus leucotrichus Coss. & Dur. seeds growing wild in SouthWest of Algeria were obtained by hydrodistillation and analysed by GC and GC-MS. Other parameters such as density, refractive index, optical rotation, freezing point, solubility in ethanol, acid value and ester index are also measured. The antifungal properties of the essential oil were conducted using biomass technique on liquid medium, mycotoxigenic test, mycelial growth, determination of minimum inhibitory concentration (MIC), sporulation and germination spores?. The essential oil was found to be active against Aspergillus flavus MTTC 2799 (Microbial Type Culture Collection and Gene Bank) and Aspergillus ochraceus CECT 2092 (Spanish Type Culture Collection). The GC and GC-MS data showed a total of 19 compounds were identified in the hydrodistilled oil. The oil was dominated by oxygenated monoteprenes represented by perilla aldehyde (81.62%).

Efficient Synthesis of N-Alkyl Polyhydroxylated Pipecolamide Compounds from d-Glucurono-6,3-lactone
Kaddour, A.; Toumieux, S.; Wadouachi, A.
Synlett 2017, 28, 2174-2178.
N-Alkyl pipecolamides were efficiently synthesized from d-glucurono-6,3-lactone via a key 5-azido N-alkylamide intermediate that can be used as a scaffold for the synthesis of 4-amino and N-sulfonated pipecolamide derivatives.

The effect of room temperature ionic liquids on the selective biocatalytic hydrolysis of chitin via sequential or simultaneous strategies
Husson, E.; Hadad, C.; Huet, G.; Laclef, S.; Lesur, D.; Lambertyn, V.; Jamali, A.; Gottis, S.; Sarazin, C.; Nguyen Van Nhien, A.
Green Chem. 2017, 19, 4122-4131.
An efficient conversion of chitin, the second most abundant renewable polymer on the Earth, into N-acetylglucosamine and N,N[prime or minute]-diacetylchitobiose, using room temperature ionic liquids (RTILs) and commercially available chitinases is described for the first time. The sequential strategy consists of the use of RTILs to pretreat chitin under mild conditions as a first step before enzymatic hydrolysis. [C2mim][OAc] (1-ethyl-3-methyl imidazolium) pretreatment provides an efficient production of N-acetylglucosamine (185.0 +/- 4.0 mg per g chitin) or N,N[prime or minute]-diacetylchitobiose (667.60 +/- 20.71 mg per g chitin) catalyzed by chitinase from Trichoderma viride or Streptomyces griseus, respectively. A thorough investigation of the structural changes of chitin induced by RTIL pretreatment suggested an increase in enzymes' accessibility to the chitin substrate. Alternatively, a one-pot enzymatic hydrolysis of chitin in [C2mim][OAc]-aqueous medium constitutes a promising simultaneous route to selectively generate N-acetylglucosamine or N,N[prime or minute]-diacetylchitobiose by decreasing the required [C2mim][OAc] amount and the number of steps. Finally, the combination of the two chitinases from T. viride and S. griseus was shown to be very relevant to considerably increase the production of N-acetylglucosamine up to 760.0 +/- 0.1 mg per g chitin.

Oligogalacturonic Acid Inhibits Vascular Calcification by Two Mechanisms: Inhibition of Vascular Smooth Muscle Cell Osteogenic Conversion and Interaction With Collagen
Hodroge, A.; Trecherel, E.; Cornu, M.; Darwiche, W.; Mansour, A.; Ait-Mohand, K.; Verissimo, T.; Gomila, C.; Schembri, C.; Da Nascimento, S.; Elboutachfaiti, R.; Boullier, A.; Lorne, E.; Courtois, J.; Petit, E.; Toumieux, S.; Kovensky, J.; Sonnet, P.; Massy, Z. A.; Kamel, S.; Rossi, C.; Ausseil, J.
Arterioscler Thromb Vasc Biol 2017, 37, 1391-1401.
OBJECTIVE: Cardiovascular diseases constitute the leading cause of mortality worldwide. Calcification of the vessel wall is associated with cardiovascular morbidity and mortality in patients having many diseases, including diabetes mellitus, atherosclerosis, and chronic kidney disease. Vascular calcification is actively regulated by inductive and inhibitory mechanisms (including vascular smooth muscle cell adaptation) and results from an active osteogenic process. During the calcification process, extracellular vesicles (also known as matrix vesicles) released by vascular smooth muscle cells interact with type I collagen and then act as nucleating foci for calcium crystallization. Our primary objective was to identify new, natural molecules that inhibit the vascular calcification process. APPROACH AND RESULTS: We have found that oligogalacturonic acids (obtained by the acid hydrolysis of polygalacturonic acid) reduce in vitro inorganic phosphate-induced calcification of vascular smooth muscle cells by 80% and inorganic phosphate-induced calcification of isolated rat aortic rings by 50%. A specific oligogalacturonic acid with a degree of polymerization of 8 (DP8) was found to inhibit the expression of osteogenic markers and, thus, prevent the conversion of vascular smooth muscle cells into osteoblast-like cells. We also evidenced in biochemical and immunofluorescence assays a direct interaction between matrix vesicles and type I collagen via the GFOGER sequence (where single letter amino acid nomenclature is used, O=hydroxyproline) thought to be involved in interactions with several pairs of integrins. CONCLUSIONS: DP8 inhibits vascular calcification development mainly by inhibition of osteogenic marker expression but also partly by masking the GFOGER sequence-thereby, preventing matrix vesicles from binding to type I collagen.

Structural characterization and rheological properties of a galactomannan from Astragalus gombo Bunge seeds harvested in Algerian Sahara
Chouana, T.; Pierre, G.; Vial, C.; Gardarin, C.; Wadouachi, A.; Cailleu, D.; Le Cerf, D.; Boual, Z.; Ould El Hadj, M. D.; Michaud, P.; Delattre, C.
Carbohydr. Polym. 2017, 175, 387-394.
A water soluble polysaccharide (WSP) was extracted and purified from Astragalus gombo seeds (Fabaceae) harvested in Septentrional Sahara (Ouargla, Algeria) with a yield of 6.8% (w/w of the dry seed ground). It was characterized by gas chromatography coupled to the mass spectrometry (GC–MS), size exclusion chromatography with Multi-Angle Light Scattering analysis (SEC-MALLS), high–resolution 1H and 13C NMR, and rheological measurements. The structural characterization indicated that this WSP fraction is a galactomannan with a mannose/galactose ratio of 1.7 formed by a backbone of β-(1,4)-d-mannopyranosyl residues (63%) substituted at O-6 position by a single α-galactopyranose residue (37%). SEC-MALLS analysis revealed that this galactomannan has an average molecular mass (Mw) of 1.1×106g/mol, an intrinsic viscosity of 860mL/g and, a random coil conformation structure. Rheological analysis in semi diluted regimes shown pseudo-plastic and viscoelastic behaviour.

Imidazolium-based titanium substrates against bacterial colonization
Cavoue, T.; Bounou Abassi, H.; Vayssade, M.; Nguyen Van Nhien, A.; Kang, I. K.; Kwon, G. W.; Pourceau, G.; Dubot, P.; Abbad Andaloussi, S.; Versace, D. L.
Biomater Sci 2017, 5, 561-569.
Nosocomial infections are often induced by the presence of pathogenic organisms on the surface of medical devices or hospital equipment. Chemical modifications of the surface are recognized as efficient strategies to prevent bacterial adhesion but they may have a negative impact on the material's interaction with living tissues. Here we have developed a photoactivated method for the modification of titanium substrates. A photoinduced technique employing a grafting-onto process has been successfully performed to covalently anchor an imidazolium-derivative siloxane onto titanium surfaces. Imidazolium surfaces showed higher bacteria-repellency performances than native titanium substrates, achieving more than 98% anti-adhesion efficiency against Escherichia coli after 24 h of incubation. In addition, these surfaces allowed for the adhesion and viability of osteoblasts cells without evidence of cytotoxicity.

Chirality inversion, supramolecular hydrogelation and lectin binding of two thiolactose amphiphiles constructed on a di-lauroyl-l-tartaric acid scaffold
Cano, M. E.; Di Chenna, P. H.; Lesur, D.; Wolosiuk, A.; Kovensky, J.; Uhrig, M. L.
New J. Chem. 2017, 41, 14754-14765.
Herein we report the synthesis, characterization and self-assembly properties of two new thiolactose based amphiphiles constructed on a di-lauroyl-l-tartaric acid scaffold that only differ in the length of the spacer by an ethylene glycol unit. Upon dissolution in hot water the amphiphiles give rise to different colloidal systems at 25 [degree]C: the one with the shorter linker forms a supramolecular thermoreversible hydrogel at a concentration of 0.1 w/v% while the other renders a colloidal system at high dilution (0.005 w/v%). Dynamic Light Scattering, Electron Microscopy (TEM, SEM and E-SEM), fluorescence CMC determination, SAXS and Circular Dichroism experiments were used to characterize both systems. The experiments indicate that only the amphiphile carrying the shorter linker is able to form a crossed-linked network of micellar fibers and thus, a stable hydrogel is observed. The difference of an ethylene glycol unit in the spacer also causes the adoption of a different molecular assembly evidenced by the inversion of the self-assembled chiral arrangement. In addition, the amphiphiles were evaluated for their ability to bind to the PNA lectin using a turbidimetric method. Agglutination was observed in both cases, a process that was disrupted upon the addition of an excess of the disaccharide lactose.

Impact of iron coordination isomerism on pyoverdine recognition by the FpvA membrane transporter of Pseudomonas aeruginosa
Bouvier, B.; Cezard, C.
Phys. Chem. Chem. Phys. 2017, 19, 29498-29507.
Pyoverdines, the primary siderophores of Pseudomonas bacteria, scavenge the iron essential to bacterial life in the outside medium and transport it back into the periplasm. Despite their relative simplicity, pyoverdines feature remarkably flexible recognition characteristics whose origins at the atomistic level remain only partially understood: the ability to bind other metals than ferric iron, the capacity of outer membrane transporters to recognize and internalize noncognate pyoverdines from other pseudomonads... One of the less examined factors behind this polymorphic recognition lies in the ability for pyoverdines to bind iron with two distinct chiralities, at the cost of a conformational switch. Herein, we use free energy simulations to study how the stereochemistry of the iron chelating groups influences the structure and dynamics of two common pyoverdines and impacts their recognition by the FpvA membrane transporter of P. aeruginosa. We show that conformational preferences for one metal binding chirality over the other, observed in solution depending on the nature of the pyoverdine, are canceled out by the FpvA transporter, which recognizes both chiralities equally well for both pyoverdines under study. However, FpvA discriminates between pyoverdines by altering the kinetics of stereoisomer interconversion. We present structural causes of this intriguing recognition mechanism and discuss its possible significance in the context of the competitive scavenging of iron.

Structural characterization and rheological behavior of a heteroxylan extracted from Plantago notata Lagasca (Plantaginaceae) seeds
Benaoun, F.; Delattre, C.; Boual, Z.; Ursu, A. V.; Vial, C.; Gardarin, C.; Wadouachi, A.; Le Cerf, D.; Varacavoudin, T.; Ould El-Hadj, M. D.; Michaud, P.; Pierre, G.
Carbohydr. Polym. 2017, 175, 96-104.
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 β-(1,3)-d-Xylp and β-(1,4)-d-Xylp highly branched, through (O)-2 and (O)-3 positions of β-(1,4)-d-Xylp by various side chains and terminal monosaccharides such as α-l-Araf-(1,3)-β-d-Xylp, β-d-Xylp-(1,2)-β-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.

The Staudinger/aza-Wittig/Grignard reaction as key step for the concise synthesis of 1-C-Alkyl-iminoalditol glycomimetics
Zoidl, M.; Gonzalez Santana, A.; Torvisco, A.; Tysoe, C.; Siriwardena, A.; Withers, S. G.; Wrodnigg, T. M.
Carbohydr. Res. 2016, 429, 62-70.
The scope of a one-pot tandem approach for the synthesis of C-1 alkyl iminoalditol derivatives with a Staudinger/aza-Wittig/Grignard cascade has been evaluated. The reaction conditions have been optimized for two azidodeoxy aldose substrates and a range of Grignard reagents. The nature of both, substrate as well as nucleophile, was found to control the stereoselectivity of the alkyl addition to the cyclic iminium intermediate at position C-1. This approach enabled the synthesis of a collection of C-alkyl iminoalditols, which were biologically evaluated as inhibitors against a set of standard glycoside hydrolases. All compounds were found to exhibit highly selective inhibition of beta-glucosidase activity.

A quantitative method to discriminate between non-specific and specific lectin-glycan interactions on silicon-modified surfaces
Yang, J.; Siriwardena, A.; Boukherroub, R.; Ozanam, F.; Szunerits, S.; Gouget-Laemmel, A. C.
J. Colloid Interface Sci. 2016, 464, 198-205.
Essential to the success of any surface-based carbohydrate biochip technology is that interactions of the particular interface with the target protein be reliable and reproducible and not susceptible to unwanted nonspecific adsorption events. This condition is particularly important when the technology is intended for the evaluation of low-affinity interactions such as those typically encountered between lectins and their monomeric glycan ligands. In this paper, we describe the fabrication of glycan (mannoside and lactoside) monolayers immobilized on hydrogenated crystalline silicon (111) surfaces. An efficient conjugation protocol featuring a key "click"-based coupling step has been developed which ensures the obtention of interfaces with controlled glycan density. The adsorption behavior of these newly developed interfaces with the lectins, Lens culinaris and Peanut agglutinin, has been probed using quantitative IR-ATR and the data interpreted using various isothermal models. The analysis reveals that protein physisorption to the interface is more prevalent than specific chemisorption for the majority of washing protocols investigated. Physisorption can be greatly suppressed through application of a strong surfactinated rinse. The coexistence of chemisorption and physisorption processes is further demonstrated by quantification of the amounts of adsorbed proteins distributed on the surface, in correlation with the results obtained by atomic force microscopy (AFM). Taken together, the data demonstrates that the nonspecific adsorption of proteins to these glycan-terminated surfaces can be effectively eliminated through the proper control of the chemical structure of the surface monolayer combined with the implementation of an appropriate surface-rinse protocol.

Affinity of Glycan-Modified Nanodiamonds towards Lectins and UropathogenicEscherichia Coli
Turcheniuk, V.; Turcheniuk, K.; Bouckaert, J.; Barras, A.; Dumych, T.; Bilyy, R.; Zaitsev, V.; Siriwardena, A.; Wang, Q.; Boukherroub, R.; Szunerits, S.
ChemNanoMat 2016, 2, 307-314.
Nanodiamond particles (NDs) modified with glycan ligands are revealing themselves to have great promise as new nanomaterials for combating biofilm formation and as promising anti-adhesive scaffolds. Currently, the strategies at hand to formulate glycan-modified NDs (glyco-NDs) are limited to a few reports. We demonstrate herein that the photoinduced covalent attachment of unmodified sugars results in glyco-NDs with high binding affinity to lectins and a uropathogenic Escherichia coli strain (E. coli UTI89). While the binding affinities of glyco-NDs to different lectins is partially sacrificed when monosaccharides such as mannose are photochemically integrated onto NDs, in the case of disaccharides and oligosaccharides the binding affinity of glyco-NDs to lectins is preserved. Moreover, mannan-modified NDs show strong interactions with uropathogenic E. coli., suggesting the effectiveness of photochemically formed glyco-NDs for disruption of E. coli-mediated biofilms.

Differentiation of Crohn's Disease-Associated Isolates from Other Pathogenic Escherichia coli by Fimbrial Adhesion under Shear Force
Szunerits, S.; Zagorodko, O.; Cogez, V.; Dumych, T.; Chalopin, T.; Alvarez Dorta, D.; Sivignon, A.; Barnich, N.; Harduin-Lepers, A.; Larroulet, I.; Yanguas Serrano, A.; Siriwardena, A.; Pesquera, A.; Zurutuza, A.; Gouin, S. G.; Boukherroub, R.; Bouckaert, J.
Biology (Basel) 2016, 5.
Shear force exerted on uropathogenic Escherichia coli adhering to surfaces makes type-1 fimbriae stretch out like springs to catch on to mannosidic receptors. This mechanism is initiated by a disruption of the quaternary interactions between the lectin and the pilin of the two-domain FimH adhesin and transduces allosterically to the mannose-binding pocket of FimH to increase its affinity. Mannose-specific adhesion of 14 E. coli pathovars was measured under flow, using surface plasmon resonance detection on functionalized graphene-coated gold interfaces. Increasing the shear had important differential consequences on bacterial adhesion. Adherent-invasive E. coli, isolated from the feces and biopsies of Crohn's disease patients, consistently changed their adhesion behavior less under shear and displayed lower SPR signals, compared to E. coli opportunistically infecting the urinary tract, intestines or loci of knee and hip prostheses. We exemplified this further with the extreme behaviors of the reference strains UTI89 and LF82. Whereas their FimA major pilins have identical sequences, FimH of LF82 E. coli is marked by the Thr158Pro mutation. Positioned in the inter-domain region known to carry hot spots of mutations in E. coli pathotypes, residue 158 is indicated to play a structural role in the allosteric regulation of type-1 fimbriae-mediated bacterial adhesion.

An efficient lactamisation/N-acyliminium Pictet-Spengler domino strategy for the diasteroselective synthesis of polyhydroxylated quinoxalinone, beta-carboline and quinazolinone derivatives
Subba Reddy, B. V.; Reddy, B. P.; Reddy, P. V.; Siriwardena, A.
Org. Biomol. Chem. 2016, 14, 4276-82.
A novel cascade strategy has been developed for the synthesis of polyhydroxylated tetrahydroindolo[1,2-a]pyrrolo[2,1-c]quinoxaline, tetrahydrodipyrrolo[1,2-a:2',1'-c]quinoxaline, hexahydro-1H-indolizino[8,7-b]indole, hexahydrobenzo[6,7]pyrrolo[1',2':1,2]azepino[3,4-b]indole, tetrahydrobenzo[4,5]imidazo[1,2-c]pyrrolo[1,2-a]quinazoline, and tetrahydropyrrolo[1,2-a]tetrazolo[1,5-c]quinazoline scaffolds. The key step is a lactamisation/Pictet-Spengler condensation of a bifunctional sugar-derived hydroxy-gamma-lactone component with an appropriate bifunctional aromatic amine component. This modular approach features the in situ-generation of a cyclic N-acyliminium intermediate that allows the diastereoselective assembly of these diverse polycyclic systems efficiently under mild and operationally simple conditions.

Towards Renewable Iodide Sources for Electrolytes in Dye-Sensitized Solar Cells
Sagaidak, I.; Huertas, G.; Nguyen Van Nhien, A.; Sauvage, F.
Energies 2016, 9, 241-256.
A novel family of iodide salts and ionic liquids based on different carbohydrate core units is herein described for application in dye-sensitized solar cell (DSC). The influence of the molecular skeleton and the cationic structure on the electrolyte properties, device performance and on interfacial charge transfer has been investigated. In combination with the C106 polypyridyl ruthenium sensitizer, power conversion efficiencies lying between 5.0% and 7.3% under standard Air Mass (A.M.) 1.5G conditions were obtained in association with a low volatile methoxypropionitrile (MPN)-based electrolyte.


Deciphering of polycationic carbohydrate based non-viral gene delivery agents by ESI-LTQ-Orbitrap using CID/HCD pairwise tandem mass spectrometry
Przybylski, C.; Benito, J. M.; Bonnet, V.; Mellet, C. O.; Garcia Fernandez, J. M.
RSC Advances 2016, 6, 78803-78817.
For almost three decades, gene therapy has been gaining interest to efficiently treat some severe diseases. In such context, the discovery of an efficient non-viral gene carrier to deliver genetic material into targeted cell nuclei is of prime importance. Numerous synthetic vectors that have been designed exhibit high transfection efficiency but also suffer from extensive cytotoxicity, thus justifying efforts to synthesize more bio-compatible ones, for example, with carbohydrate scaffolds. In this sense, cyclodextrins (CDs) are well known to present low to very low cytotoxicity in humans and have potential, after polycationization, to serve as suitable compaction/transfection agents for RNA/DNA. However, such polycationic CDs must be accurately characterized to establish a straightforward structure-biological activity relationship which is guided by the nitrogen/phosphorus ratio (N/P). In the study herein, we demonstrated that electrospray-(tandem) mass spectrometry (ESI-(MS)MS) combining Collision Induced Dissociation (CID) and Higher Collision induced Dissociation (HCD) is a useful tool for such synthetic agent characterization. The suitability of CID/HCD pairwise combination was investigated for the structural deciphering of five representative members of a polycationic cyclodextrin library. Our approach allows for easy access to content, type and localisation of amino groups thereby offering a useful tool to correlate the synthetic delivery agent with effective compaction of oligo-/polynucleotides.

Improvement of Gold-Catalyzed Oxidation of Free Carbohydrates to Corresponding Aldonates Using Microwaves
Omri, M.; Pourceau, G.; Becuwe, M.; Wadouachi, A.
ACS Sustainable Chemistry & Engineering 2016, 4, 2432-2438.
An efficient microwave-assisted methodology for the oxidation of free carbohydrates to corresponding aldonates is described. Supported gold catalyst, hydrogen peroxide and a mineral base were used to perform the oxidation reaction in water under microwave irradiation. These conditions combined with Au/Al2O3 catalyst allowed to reach in 10 minutes a quantitative conversion of glucose.The catalyst was highly selective and reusable and only 0.004 mol % of gold compared to sugar was used. The reaction was performed using a variety of substrates (mono or oligosaccharides, neutral or acidic sugars) and good to excellent conversion yields and selectivity to corresponding aldonates were obtained. After filtration and freeze-drying, sodium or potassium aldonates were obtained without any purification. Thanks to very high turn-over frequencies (up to 438 000 h-1), this methodology improves significantly the previously described methods for the gold-catalyzed oxidation of carbohydrates.

Synthesis and Applications of Silyl 2-Methylprop-2-ene-1-sulfinates in Preparative Silylation and GC-Derivatization Reactions of Polyols and Carbohydrates
Markovic, D.; Tchawou, W. A.; Novosjolova, I.; Laclef, S.; Stepanovs, D.; Turks, M.; Vogel, P.
Chemistry 2016, 22, 4196-205.
Trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, and triisopropylsilyl 2-methylprop-2-ene-1-sulfinates were prepared through (CuOTf)2C6H6-catalyzed sila-ene reactions of the corresponding methallylsilanes with SO2 at 50 degrees C. Sterically hindered, epimerizable, and base-sensitive alcohols gave the corresponding silyl ethers in high yields and purities at room temperature and under neutral conditions. As the byproducts of the silylation reaction (SO2 +isobutylene) are volatile, the workup was simplified to solvent evaporation. The developed method can be employed for the chemo- and regioselective semiprotection of polyols and glycosides and for the silylation of unstable aldols. The high reactivity of the developed reagents is shown by the synthesis of sterically hindered per-O-tert-butyldimethylsilyl-alpha-D-glucopyranose, the X-ray crystallographic analysis of which is the first for a per-O-silylated hexopyranose. The per-O-silylation of polyols, hydroxy carboxylic acids, and carbohydrates with trimethylsilyl 2-methylprop-2-ene-1-sulfinate was coupled with the GC analysis of nonvolatile polyhydroxy compounds both qualitatively and quantitatively.

Catalytic Synthesis of a New Series of Alkyl Uronates and Evaluation of Their Physicochemical Properties
Lu, H.; Drelich, A.; Omri, M.; Pezron, I.; Wadouachi, A.; Pourceau, G.
Molecules 2016, 21, 1301-1315.
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 β-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
Lu, B.; Vayssade, M.; Miao, Y.; Chagnault, V.; Grand, E.; Wadouachi, A.; Postel, D.; Drelich, A.; Egles, C.; Pezron, I.
Colloids Surf B Biointerfaces 2016, 145, 79-86.
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.

Glycochemical Applications of Diels-Alder Reaction
Laclef, S.; Toumieux, S.; Kovensky, J.
Curr. Org. Chem. 2016, 20, 2379-2392.
Carbohydrates and their analogs are key molecules with a wide range of biological activities. These bioactive compounds are usually synthesized through derivatization of naturally occurring carbohydrates. Nevertheless, this strategy suffers from a limited range of naturally available monosaccharide building blocks and the necessity of laborious steps of protection and deprotection. Consequently new methods began to emerge and Diels-Alder reaction appeared to be a method of choice for their de novo production. The synthesis of carbohydrates and their analogs by means of cycloaddition reactions will be reviewed here. Moreover the potentiality of the use of monosaccharides to induce chirality in Diels-Alder reaction will be presented. Efficient methods for the synthesis of di- and tri-saccharides using the developments shown previously will be also introduced.

Chapter 5 Recent Advances in the Synthesis of Sugar-based Surfactants
Kovensky, J.; Grand, E.
Biomass Sugars for Non-Fuel Applications 2016, 159-204.
New challenges have to be faced in the field of surfactants. Green processes and products are increasingly demanded: green syntheses, natural building blocks as starting materials, products of high biodegradability and devoid of toxicity, low costs. Sugar-based surfactants successfully fit all these requirements and thus they are at the centre of the research of new green surfactants with specific properties. Most of the syntheses published in the literature from 2008 to 2014 are about new structures presenting variations on the sugar moiety, the hydrophobic chain, and the introduction of spacer arms between the polar head and the lipophilic tail. Carbohydrates offer a wide diversity of monomers and dimers that can be cyclic (furanose, pyranose) or acyclic to be used as a polar head. Among all the available hydroxyl groups of a sugar unit, two are particularly suitable for substitution: primary alcohols and the hydroxyl at the anomeric position. The hydrophobic chain can be more complex than the classical alkyl chain, as chemists are looking for new properties that can be brought by the use of fluoroalkyl chains or polysiloxanes. This chapter reviews recent bibliography and reports (patents excluded) on the synthesis of sugar-based surfactants, including chemical and chemoenzymatic methods.

Consequences of Solid Electrolyte Interphase (SEI) Formation upon Aging on Charge-Transfer Processes in Dye-Sensitized Solar Cells
Flasque, M.; Nhien, A. N. V.; Moia, D.; Barnes, P. R. F.; Sauvage, F.
The Journal of Physical Chemistry C 2016, 120, 18991-18998.
Solid electrolyte interphase (SEI) layers form on sensitized-TiO2 photoanodes and platinum counter electrodes when dye-sensitized solar cells (DSSCs) are subjected to an accelerated aging protocol (e.g., heating at 85 °C in the dark for 500 h). To understand how this impacts device operation, we conducted an electrochemical impedance spectroscopy study and found that the SEI induces an additional electron-transfer process from the TiO2 to the electrolyte. This is materialized by the onset of a new charge-transfer semicircle at higher frequencies, predominantly visible under bias voltages similar to and greater than the open-circuit voltage. Our results emphasize the detrimental role of SEI formation on device performance and lifetime. Additionally, nanosecond transient absorption spectroscopy showed that SEI formation reduced the rate of oxidized dye regeneration. We also found that a proportion of the photogenerated holes on the dyes were transferred to the SEI itself. A prolonged aging duration led to the electrode’s mesoporosity network being entirely clogged by the SEI, thus impeding efficient transport of the electrolyte redox couple and being responsible for a further decline in photovoltaic performances.

Reversible anion intercalation in a layered aromatic amine: a high-voltage host structure for organic batteries
Deunf, E.; Moreau, P.; Quarez, E.; Guyomard, D.; Dolhem, F.; Poizot, P.
J. Mater. Chem. A 2016, 4, 6131-6139.
Cation insertion reactions in inorg. host frameworks are well-established phenomena. Over the last 40 years, a myriad of examples have been documented, which have given rise to key applications such as for electrochem. storage devices. By contrast, materials able to reversibly insert anions into their host lattice are rare, and consist essentially of graphite intercalation compds. (GICs), thus limiting their potential use. Org. materials, conversely, if properly designed, could pave the way for future developments in anionic insertion electrochem., by virtue of the rational incorporation of p-type redox-active org. moieties. Here, we report the discovery of a p-type org. host lattice based on a simple crystd. arom. diamine. The reversible anion insertion process relies on the electrochem. activity of neutral secondary amino groups incorporated into a robust terephthalate backbone. XRD, TEM and EELS studies reveal the attainment of a unique lamellar structure conducive to the oxidative insertion of anions (including the bulky TFSI-). In a dual-ion cell configuration using lithium as the neg. electrode, this org. structure can react reversibly at high operating potential (〈E〉 ≈ 3.22 V vs. Li+/Li) with good cycling performance even without carbon addn., hence generating further avenues for the development of org. batteries and more generally, the field of intercalation chem.

The origin of the stereoselective alkylation of 3-substituted-2-oxopiperazines: A computational investigation
Cézard, C.; Bouvier, B.; Dassonville-Klimpt, A.; Sonnet, P.
Computational and Theoretical Chemistry 2016, 1078, 1-8.
2-Oxopiperazines and their derivatives are important pharmacophores found in numerous bioactive products. The potency of these compounds depends on the nature and/or position of their substituent(s) as well as on their chirality. Hence, it is important to develop, control and optimize synthetic routes leading to enantiomerically pure substituted 2-oxopiperazines. In this work we report on the origin of this stereoselectivity, upon alkylation of 2-oxopiperazines at position C3, studied by means of quantum chemistry calculations. Indeed, this alkylation with methyl chloride is predicted to afford mainly the exo product with a 98:2 ratio. To this purpose, we model the reaction path leading to both enantiomers by scrutinizing the structures and energetics of the pre-reaction complexes, the transition states and the post-reaction complexes. The computational results are in good agreement with the experimental observations, and provide valuable insights into the origins of this specificity. From the conformational analysis of the piperazine ring and of intramolecular interaction patterns, we show that the enantiofacial discrimination is achieved by a subtle balance between sterical hindrance and control of the conformation of the piperazine ring.

Optimizing the Multivalent Binding of the Bacterial Lectin LecA by Glycopeptide Dendrimers for Therapeutic Purposes
Bouvier, B.
J. Chem. Inf. Model. 2016, 56, 1193-1204.
Bacterial lectins are nonenzymic sugar-binding proteins involved in the formation of biofilms and the onset of virulence. The weakness of individual sugar-lectin interactions is compensated by the potentially large no. of simultaneous copies of such contacts, resulting in high overall sugar-lectin affinities and marked specificities. Therapeutic compds. functionalized with sugar residues can compete with the host glycans for binding to lectins only if they are able to take advantage of this multivalent binding mechanism. Glycopeptide dendrimers, featuring treelike topologies with sugar moieties at their leaves, have already shown great promise in this regard. However, optimizing the dendrimers' amino acid sequence is necessary to match the dynamics of the lectin active sites with that of the multivalent ligands. This work combines long-time-scale coarse-grained simulations of dendrimers and lectins with a reasoned exploration of the dendrimer sequence space in an attempt to suggest sequences that could maximize multivalent binding to the galactose-specific bacterial lectin LecA. These candidates are validated by simulations of mixed dendrimer/lectin solns., and the effects of the dendrimers on lectin dynamics are discussed. This approach is an attractive first step in the conception of therapeutic compds. based on the dendrimer scaffold and contributes to the understanding of the various classes of multivalency that underpin the ubiquitous "sugar code".

Radical Coupling Allows a Fast and Tuned Synthesis of Densely Packed Polyrotaxanes Involving γ-Cyclodextrins and Polydimethylsiloxane
Blin, F.; Przybylski, C.; Bonnet, V.; Clément, M.-J.; Curmi, P. A.; Choppinet, P.; Nakajima, T.; Chéradame, H.; Jarroux, N.
Macromolecules 2016, 49, 3232-3243.
The first radical end-coupling synthesis of polydimethylsiloxane (PDMS)−γ-cyclodextrins (γ-CDs) based polyrotaxane is reported. Conversely to usual chemical way, the radical process leads to fast both controlled size and structure with minimal side reaction while exhibiting very high conversion rate (w/w, 80%). Pure PDMS−γ-CDs molecular necklaces were successfully isolated by preparative size exclusion chromatography and finely characterized both by 1D/2D/STD 1H and 13C NMR and MALDI-TOF mass spectrometry. The observations give clear evidence of the supramolecular assembly synthesis where the filling ratio (γ-CD/monomer unit) of PDMS chains is as high as 40% of γ-CDs. Combination of such radical-based coupling supported by detailed analytical characterizations appears at the forefront of a fast, suitable, and easily amenable scaling-up CDs-based polyrotaxane synthesis process.

Asymmetric synthesis of new antimalarial aminoquinolines through Sharpless aminohydroxylation
Bentzinger, G.; De Souza, W.; Mullié, C.; Agnamey, P.; Dassonville-Klimpt, A.; Sonnet, P.
Tetrahedron: Asymmetry 2016, 27, 1-11.
Recently, the asymmetric synthesis and biological activity of (R)- and (S)-4-aminoquinolinemethanols 1 as mefloquine analogues were reported. Several compounds showed very promising antimalarial activity, in the nanomolar range, against Plasmodium falciparum 3D7 and W2. Enantiomers with an (S)-absolute configuration were more active than their (R)-counterparts by a factor ranging from 2 to 15-fold, according to the compound and the plasmodial strain considered. In continuation of our work, three novel series of enantiopure aminoquinolines 2a, 2b, and 3 were synthesized via an asymmetric aminohydroxylation reaction. These compounds were obtained in 2 or 4 steps from a common amidoalcohol key-intermediate 4. They displayed IC50 values close to the micromolar against the two P. falciparum strains 3D7 and W2. The study of the structure–activity relationships allows us to better understand the importance of the substitution and of the stereochemistry at C11 and C12 position of the quinoline and gives tracks for the design of new compounds more active against the plasmodial strains.

Multivalent sialylation of β-thio-glycoclusters by Trypanosoma cruzi trans sialidase and analysis by high performance anion exchange chromatography
Agustí, R.; Cano, M. E.; Cagnoni, A. J.; Kovensky, J.; de Lederkremer, R. M.; Uhrig, M. L.
Glycoconjugate J. 2016, 1-10.
The synthesis of multivalent sialylated glycoclusters is herein addressed by a chemoenzymatic approach using the trans-sialidase of Trypanosoma cruzi (TcTS). Multivalent β-thio-galactopyranosides and β-thio-lactosides were used as acceptor substrates and 3′-sialyllactose as the sialic acid donor. High performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) was shown to be an excellent technique for the analysis of the reaction products. Different eluting conditions were optimized to allow the simultaneous resolution of the sialylated species, as well as their neutral precursors. The TcTS efficiently transferred sialyl residues to di, tri, tetra and octa β-thiogalactosides. In the case of an octavalent thiolactoside, up to six polysialylated compounds could be resolved. Preparative sialylation reactions were performed using the tetravalent and octavalent acceptor substrates. The main sialylated derivatives could be unequivocally assigned by MALDI mass spectrometry. Inhibition of the transfer to the natural substrate, N-acetyllactosamine, was also studied. The octalactoside caused 82 % inhibition of sialic acid transfer when we used equimolar concentrations of donor, acceptor and inhibitor.

Carbohydrate microarray for the detection of glycan-protein interactions using metal-enhanced fluorescence
Yang, J.; Moraillon, A.; Siriwardena, A.; Boukherroub, R.; Ozanam, F.; Gouget-Laemmel, A. C.; Szunerits, S.
Anal. Chem. 2015, 87, 3721-8.
Carbohydrate arrays are potentially one of the most attractive tools to study carbohydrate-based interactions. This paper describes a new analytical platform that exploits metal-enhanced fluorescence for the sensitive and selective screening of carbohydrate-lectin interactions. The chip consists of a glass slide covered with gold nanostructures, postcoated with a thin layer of amorphous silicon-carbon alloy (a-Si0.8C0.2:H). An immobilization strategy based on the formation of a covalent bond between propargyl-terminated glycans and surface-linked azide groups was used to attach various glycans at varying surface densities onto the interface and to fabricate a carbohydrate array via efficient local "click" chemistry strategy. The specific association of the new interface with fluorescently labeled lectins was assessed by fluorescence imaging and an excellent selectivity to specific proteins was achieved. Optimization of the surface architecture and the plasmonic transducer resulted in an enhancement of the fluorescence intensity by 1 order of magnitude, when compared to the corresponding substrate devoid of gold nanostructures. The limit of detection (LOD) of such microarrays is in the picomolar range, making it a promising system for development in pharmaceutical or biomedical applications.

Unprecedented inhibition of glycosidase-catalyzed substrate hydrolysis by nanodiamond-grafted O-glycosides
Siriwardena, A.; Khanal, M.; Barras, A.; Bande, O.; Mena-Barragán, T.; Mellet, C. O.; Garcia Fernández, J. M.; Boukherroub, R.; Szunerits, S.
RSC Adv. 2015, 5, 100568-100578.
We report herein the unprecedented finding that [small alpha]-O-glucosides and also [small alpha]-O-mannosides, when conjugated on nanodiamond particles (ND), are not only stable towards the hydrolytic action of the corresponding matching glycosidases, but are also endowed with the ability to inhibit them. Moreover, conjugation of the O-glycosides to ND (glyco-ND) sees them transformed into inhibitors of mismatching enzymes (for which they do not serve as substrates even when in their monovalent, free form). The effects of the glyco-NDs have been demonstrated on a panel of commercial glycosidases and the inhibition found to be competitive and reversible and not to be related to any denaturation of enzymes by the ND-conjugates. Values for Ki in the low micromolar range have been measured for certain glyco-ND (for example, a Ki value of 5.5 +/- 0.2 [small mu ]M was measured for the glucopyranosyl-coated NDs against the [small alpha]-glucosidase from baker's yeast) and found to depend on both the identity of the enzyme and the glyco-ND. The latter Ki value compares well with that obtained for the natural glucosidase inhibitor, 1-deoxynojirimycin (Ki of 25 [small mu ]M against the [small alpha]-glucosidase from baker's yeast under identical assay conditions). The monovalent control O-glycosides was hydrolysed efficiently by the appropriate glycosidase. Glyco-ND bearing 50% loading of O-glycoside as well ND conjugated with both O-glucosides and O-mannosides (mixed) have also been assayed and shown also to inhibit the panel of glycosidases with potencies and selectivities different from those recorded for the 100% loaded ND and also from one another. The impact on factors such as glycotope density and heteromultivalency on inhibition is reminiscent of that typically encountered in carbohydrate-lectin recognition events. The abilities of the glyco-ND to bind, cross-link and aggregate concanavalin A, a lectin known to recognize both [small alpha]-O-d-mannosides and [small alpha]-O-d-glucosides, was assessed by a range of methods including an enzyme-linked lectin assay (ELLA), a two-site sandwich ELLA and a turbidimetry assay, respectively and indeed seen to reflect their expected per glycotope affinity enhancements as compared to monovalent controls: the high avidity of the lectin for each respective glycosylated ND particle was consistent with the manifestation of potent multivalent effects driving lectin recognition and binding.

Wnt/beta-catenin signaling mediates osteoblast differentiation triggered by peptide-induced alpha5beta1 integrin priming in mesenchymal skeletal cells
Saidak, Z.; Le Henaff, C.; Azzi, S.; Marty, C.; Da Nascimento, S.; Sonnet, P.; Marie, P. J.
J. Biol. Chem. 2015, 290, 6903-12.
The alpha5beta1 integrin is a key fibronectin (FN) receptor that binds to RGD-containing peptides to mediate cell adhesion. We previously reported that alpha5beta1 integrin promotes osteogenic differentiation in mesenchymal skeletal cells (MSCs), but the underlying mechanisms are not fully understood. In this study, we determined the signaling mechanisms induced by alpha5beta1 integrin interaction with its high-affinity ligand CRRETAWAC in murine and human MSCs and in vivo. We show that cyclized CRRETAWAC fully displaced MSC adhesion to FN, whereas related peptides lacking the full RRET sequence produced a partial displacement, indicating that RRET acts as an RGD-like sequence that is required to antagonize FN-mediated cell adhesion. However, all peptides increased focal adhesion kinase phosphorylation, OSE2 transcriptional activity, osteoblast gene expression, and matrix mineralization in MSCs, indicating that peptide-induced alpha5beta1 integrin priming can promote osteogenic differentiation independently of the RRET sequence. Biochemical analyses showed that peptide-induced alpha5beta1 integrin priming transiently increased PI3K/Akt phosphorylation and promoted Wnt/beta-catenin transcriptional activity independently of RRET. Consistently, pharmacological inhibition of PI3K activity reduced osteoblast differentiation and abolished Wnt regulatory gene expression induced by alpha5beta1 integrin priming. In vivo, systemic delivery of cyclized GACRETAWACGA linked to (DSS)6 to allow delivery to bone-forming sites for 6 weeks increased serum osteocalcin levels and improved long bone mass and microarchitecture in SAMP-6 senescent osteopenic mice. The results support a mechanism whereby alpha5beta1 integrin priming by high-affinity ligands integrates Wnt/beta-catenin signaling to promote osteoblast differentiation independently of cell adhesion, which could be used to improve bone mass and microarchitecture in the aging skeleton.

Probing the common alkali metal affinity of native and variously methylated [small beta]-cyclodextrins by combining electrospray-tandem mass spectrometry and molecular modeling
Przybylski, C.; Bonnet, V.; Cezard, C.
Phys. Chem. Chem. Phys. 2015, 17, 19288-19305.
In the study herein, we investigated the solution and gas phase affinity of native and variously methylated [small beta]-cyclodextrins (CDs) as hosts towards three common alkali metals as guests namely lithium, sodium and potassium. For this purpose, two complementary approaches have been employed: electrospray-tandem mass spectrometry (ESI-MS/MS) with two energetic regimes: Collision Induced Dissociation (CID) and Higher Collision Dissociation (HCD), respectively, and DFT molecular modeling. These approaches have been achieved by taking into account the interaction of either one or two alkali metals with the host molecules. The results showed a good agreement between experimental and theoretical data. It was demonstrated that increasing the methylation degree strengthened the gas phase affinity towards all studied alkali metals. Furthermore, it was established that the cation selectivity was Na+ > Li+ > K+ and Li+ > Na+ > K+ for the solution and gas phase, respectively.

Chapter 6 - Perspectives in Lithium Batteries A2 - Chagnes, Alexandre
Poizot, P.; Dolhem, F.; Gaubicher, J.; Renault, S.
Lithium Process Chemistry 2015, 191-232.
Abstract Li-ion batteries still fall short of fulfilling the ever-increasing storage needs while keeping their environmental footprint as low as possible. In this chapter, without being exhaustive we tackle what next promising Li-based battery technologies could be; through the implementation of alternative (electro)chemistries including the use of more abundant components and/or less-polluting processing solutions. Li-chalcogen (O2 and S) batteries are presented herein as quite promising systems especially for the market of electrically powered vehicles thanks to particularly high (expected) energy density values. Li-aqueous batteries, beyond the obvious environmental benefit in using water-based electrolytes, offer also some attractive perspectives to promote low-cost electrical storage solutions, potentially interesting for stationary applications. Finally, electroactive organic compounds could play an important role in the forthcoming battery technologies, since they exhibit several assets such as the possibility of being prepared from renewable resources and eco-friendly processes coupled with a simplified recycling management.

Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery
Merino, F.; Bouvier, B.; Cojocaru, V.
PLoS Comput. Biol. 2015, 11, e1004287.
Author Summary

Pluripotent stem cells can give rise to all somatic lineages. When taken out of the context of the embryo they can be maintained and for this a core transcriptional regulatory circuitry is crucial. OCT4 and SOX2, two factors of this network, are also critical for the induction of pluripotency in somatic cells. In pluripotent cells, OCT4 and SOX2 associate on DNA regulatory regions, enhancing or modifying each other's sequence specificity. In contrast, in the early stages during induction of pluripotency, it was proposed that OCT4 explores the genome independent of SOX2. Here we report the mechanism by which SOX2 influences the orientation, dynamics, and unbinding free energy profile of OCT4. This involves an interplay of protein-protein interactions and DNA-mediated allostery. We consider that this mechanism enables OCT4 to use its DNA binding domains and the interaction partners available in a certain biological context to access alternative genome exploration routes. This study enhances the understanding of the context specific function of OCT4 and provides a general perspective on how DNA-binding cooperativity is modulated by different types of interactions.


A rechargeable lithium/quinone battery using a commercial polymer electrolyte
Lecuyer, M.; Gaubicher, J.; Barres, A.-L.; Dolhem, F.; Deschamps, M.; Guyomard, D.; Poizot, P.
Electrochem. Commun. 2015, 55, 22-25.
The present study reports superior electrochem. performance with capacity doubled for org. pos. electrodes based on a small redox-active mol. when using the Lithium Metal Polymer (LMP) technol. Particularly, the simple use of the regular solid polymer electrolyte currently employed in com. LMP cells allows obtaining for the first time an efficient two-electron cycling of tetramethoxy-p-benzoquinone with high-rate capability at temps. as high as 100 °C. With no optimization, the restored capacity represents 80% of the theor. value (190 mAh/g) after 20 cycles operated at a C rate. On the contrary, when cycled in conventional carbonate-based electrolytes, this quinone compd. exhibits quite poor electrochem. features such as a very limited depth of discharge (∼ 50% of the theor. capacity in the first cycle) followed by rapid capacity decay. After cycling, preliminary post-mortem characterizations did not evidence any obvious degrdn. in the cell. Although the adverse effect of the diffusion of the active material is not fully inhibited, the coulombic efficiency is close to 100% while the Li/electrolyte interface appears stable.

Ligand-free Pd-catalyzed and copper-assisted C-H arylation of quinazolin-4-ones with aryl iodides under microwave heating
Laclef, S.; Harari, M.; Godeau, J.; Schmitz-Afonso, I.; Bischoff, L.; Hoarau, C.; Levacher, V.; Fruit, C.; Besson, T.
Org. Lett. 2015, 17, 1700-3.
A microwave-assisted method for the palladium-catalyzed direct arylation of quinazolin-4-one has been developed under copper-assistance. This method is applicable to a wide range of aryl iodides and substituted (2H)-quinazolin-4-ones. This protocol provides a simple and efficient way to synthesize biologically relevant 2-arylquinazolin-4-one backbones.

Toward multifunctional "clickable" diamond nanoparticles
Khanal, M.; Turcheniuk, V.; Barras, A.; Rosay, E.; Bande, O.; Siriwardena, A.; Zaitsev, V.; Pan, G. H.; Boukherroub, R.; Szunerits, S.
Langmuir 2015, 31, 3926-33.
Nanodiamonds (NDs) are among the most promising new carbon based materials for biomedical applications, and the simultaneous integration of various functions onto NDs is an urgent necessity. A multifunctional nanodiamond based formulation is proposed here. Our strategy relies on orthogonal surface modification using different dopamine anchors. NDs simultaneously functionalized with triethylene glycol (EG) and azide (-N3) functions were fabricated through a stoichiometrically controlled integration of the dopamine ligands onto the surface of hydroxylated NDs. The presence of EG functionalities rendered NDs soluble in water and biological media, while the -N3 group allowed postsynthetic modification of the NDs using "click" chemistry. As a proof of principle, alkynyl terminated di(amido amine) ligands were linked to these ND particles.

Inhibition of type 1 fimbriae-mediated Escherichia coli adhesion and biofilm formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles
Khanal, M.; Larsonneur, F.; Raks, V.; Barras, A.; Baumann, J. S.; Martin, F. A.; Boukherroub, R.; Ghigo, J. M.; Ortiz Mellet, C.; Zaitsev, V.; Garcia Fernandez, J. M.; Beloin, C.; Siriwardena, A.; Szunerits, S.
Nanoscale 2015, 7, 2325-35.
Recent advances in nanotechnology have seen the development of a number of microbiocidal and/or anti-adhesive nanoparticles displaying activity against biofilms. In this work, trimeric thiomannoside clusters conjugated to nanodiamond particles (ND) were targeted for investigation. NDs have attracted attention as a biocompatible nanomaterial and we were curious to see whether the high mannose glycotope density obtained upon grouping monosaccharide units in triads might lead to the corresponding ND-conjugates behaving as effective inhibitors of E. coli type 1 fimbriae-mediated adhesion as well as of biofilm formation. The required trimeric thiosugar clusters were obtained through a convenient thiol-ene "click" strategy and were subsequently conjugated to alkynyl-functionalized NDs using a Cu(I)-catalysed "click" reaction. We demonstrated that the tri-thiomannoside cluster-conjugated NDs (ND-Man3) show potent inhibition of type 1 fimbriae-mediated E. coli adhesion to yeast and T24 bladder cells as well as of biofilm formation. The biofilm disrupting effects demonstrated here have only rarely been reported in the past for analogues featuring such simple glycosidic motifs. Moreover, the finding that the tri-thiomannoside cluster (Man3N3) is itself a relatively efficient inhibitor, even when not conjugated to any ND edifice, suggests that alternative mono- or multivalent sugar-derived analogues might also be usefully explored for E. coli-mediated biofilm disrupting properties.

Arylnaphthalene and aryltetralin-type lignans in hairy root cultures of Linum perenne, and the stereochemistry of 6-methoxypodophyllotoxin and one diastereoisomer by HPLC-MS and NMR spectroscopy
Jullian-Pawlicki, N.; Lequart-Pillon, M.; Huynh-Cong, L.; Lesur, D.; Cailleu, D.; Mesnard, F.; Laberche, J. C.; Gontier, E.; Boitel-Conti, M.
Phytochem. Anal. 2015, 26, 310-9.
INTRODUCTION: Hairy root cultures of Linum sp. are an alternative for the high production of lignans. Linum perenne is known to produce arylnaphthalene-type lignans such as justicidin B, isojusticidin and diphyllin. OBJECTIVE: To elucidate the presence of aryltetralin-type lignan diastereoisomers, besides the known arylnaphthalene-type lignans, in hairy roots of Linum perenne, and to determine the configurations of one diastereoisomer of 6-methoxypodophyllotoxin (6-MPTOX). METHODS: Lignans from hairy root cultures of Linum perenne were extracted and separated by HPLC. Arylnaphthalene-type lignans were identified by LC-MS, according to the literature. Two diastereoisomers of aryltetralin-type lignans were analysed by mass spectrometry and NMR spectroscopy. RESULTS: Numerous arylnaphthalene-type lignans (diphyllin-2-hexose-pentose, diphyllin-3-pentose and diphyllin-hexose) were identified in hairy root cultures. Methoxypodophyllotoxin, an aryltetralin-type lignan, was also identified, as well as one diastereoisomer. This aryltetralin-type lignan could be derived via 7-hydroxymatairesinol as a hypothetical biosynthetic pathway. The stereochemical configurations of aryltetralin isomers were determined. CONCLUSION: Arylnaphthalene and two diastereoisomers of aryltetralin-type lignans are produced in Linum perenne hairy root cultures. Matairesinol, the precursor of justicidin B, also seems to be converted into 6-MPTOX via 7-hydroxymatairesinol. This is the first report of the stereochemical configurations of an aryltetralin-type lignan other than podophyllotoxin (PTOX).

Cu/Pd-Catalyzed C-2-H Arylation of Quinazolin-4(3H)-ones with (Hetero)aryl Halides
Godeau, J.; Harari, M.; Laclef, S.; Deau, E.; Fruit, C.; Besson, T.
Eur. J. Org. Chem. 2015, 2015, 7705-7717.
The regiospecific C-2-H arylation of N-3-substituted quinazolin-4(3H)-ones with a wide range of aryl or (hetero)aryl halides under microwave irradn. was studied. A ligand-dependent palladium/copper bicatalytic system was developed and allowed direct cross-coupling with a variety of (hetero)aryl halides. This useful and scalable procedure promotes the construction of C(sp2)-C(sp2) bonds from arenes or (hetero)arenes and aryl or (hetero)aryl bromides and chlorides in a time-efficient strategy. The extension of the reaction to various N-3-substituted quinazolin-4(3H)-ones with iodobenzene as well as the scope and limitations of the method were also investigated.

Reactivity of D-fructose and D-xylose in acidic media in homogeneous phases
Fusaro, M. B.; Chagnault, V.; Postel, D.
Carbohydr. Res. 2015, 409, 9-19.
Chemistry development of renewable resources is a real challenge. Carbohydrates from biomass are complex and their use as substitutes for fossil materials remains difficult (European involvement on the incorporation of 20% raw material of plant origin in 2020). Most of the time, the transformation of these polyhydroxylated structures are carried out in acidic conditions. Recent reviews on this subject describe homogeneous catalytic transformations of pentoses, specifically toward furfural, and also the transformation of biomass-derived sugars in heterogeneous conditions. To complete these informations, the objective of this review is to give an overview of the structural variety described during the treatment of two monosaccharides (D-Fructose and D-xylose) in acidic conditions in homogeneous phases. The reaction mechanisms being not always determined with certainty, we will also provide a brief state of the art regarding this.

Metal-Free Oxidative Lactonization of Carbohydrates Using Molecular Iodine
Fusaro, M.; Chagnault, V.; Josse, S.; Drillaud, N.; Anquetin, G.; Postel, D.
Carbohydrate Chemistry 2015, 33-38.
Presents reliable and tested protocols for preparation of intermediates for carbohydrate synthesis Offers a unique resource in carbohydrate chemistry, compiling useful information in one reference Explores carbohydrate chemistry from both the academic and industrial points of view Features contributions from world-renowned experts and is overseen by a highly respected series editor

Metal-Free, Diamine-Mediated, Oxidative Monoamidation of Benzylated Carbohydrates
Fusaro, M.; Chagnault, V.; Dussouy, C.; Postel, D.
Carbohydrate Chemistry 2015, 27-32.
Presents reliable and tested protocols for preparation of intermediates for carbohydrate synthesis Offers a unique resource in carbohydrate chemistry, compiling useful information in one reference Explores carbohydrate chemistry from both the academic and industrial points of view Features contributions from world-renowned experts and is overseen by a highly respected series editor

Synthesis of high-mannose oligosaccharide analogues through click chemistry: true functional mimics of their natural counterparts against lectins?
Francois-Heude, M.; Mendez-Ardoy, A.; Cendret, V.; Lafite, P.; Daniellou, R.; Ortiz Mellet, C.; Garcia Fernandez, J. M.; Moreau, V.; Djedaini-Pilard, F.
Chemistry 2015, 21, 1978-91.
Terminal "high-mannose oligosaccharides" are involved in a broad range of biological and pathological processes, from sperm-egg fusion to influenza and human immunodeficiency virus infections. In spite of many efforts, their synthesis continues to be very challenging and actually represents a major bottleneck in the field. Whereas multivalent presentation of mannopyranosyl motifs onto a variety of scaffolds has proven to be a successful way to interfere in recognition processes involving high-mannose oligosaccharides, such constructs fail at reproducing the subtle differences in affinity towards the variety of protein receptors (lectins) and antibodies susceptible to binding to the natural ligands. Here we report a family of functional high-mannose oligosaccharide mimics that reproduce not only the terminal mannopyranosyl display, but also the core structure and the branching pattern, by replacing some inner mannopyranosyl units with triazole rings. Such molecular design can be implemented by exploiting "click" ligation strategies, resulting in a substantial reduction of synthetic cost. The binding affinities of the new "click" high-mannose oligosaccharide mimics towards two mannose specific lectins, namely the plant lectin concanavalin A (ConA) and the human macrophage mannose receptor (rhMMR), have been studied by enzyme-linked lectin assays and found to follow identical trends to those observed for the natural oligosaccharide counterparts. Calorimetric determinations against ConA, and X-ray structural data support the conclusion that these compounds are not just another family of multivalent mannosides, but real "structural mimics" of the high-mannose oligosaccharides.

Octyl glucoside derivatives: A tool against metal pollutants
Ferlin, N.; Grassi, D.; Ojeda, C.; Castro, M. J. L.; Cirelli, A. F.; Kovensky, J.; Grand, E.
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2015, 480, 439-448.
Derivatives of octyl glucoside modified by the introduction of a chemical function (carboxylic acid, hydroxamic acid) able to enhance the complexing properties of the surfactants toward metallic cations have been used as flotation collectors to remove various metallic cations from a water phase. Flotation experiments at the laboratory scale were performed on Fe(III), Cu(II), Cr(III), Cd(II), Zn(II), Ni(II) and As(III) aqueous solutions. The most interesting results were obtained in the extraction of Fe(III) and Cu(II). Interfacial properties were studied, and the effect of the polar head structure and anomeric configuration was analyzed. Structural variations have an influence on the efficiency and the foaming ability of these compounds. The introduction of a chelating functionality preserves the interfacial performances of these surfactants. Complexes equilibrium constants and species distribution diagrams for Fe(III) and the best flotation agents 2a and 2b were determined from multi-wavelength spectrophotometric pH titration. Both compounds showed analogous values for log β1, log β2 and log β3. The bidentanted Fe(III)-hydroxamate species (2:1 surfactant-metal ratio) reached a maximum concentration in the pH range of 5.5-6.5. At this pH, the best results in the flotation experiments were obtained for both compounds.

SiO2/Ionic Liquid Hybrid Nanoparticles for Solid-State Lithium Ion Conduction
Delacroix, S.; Sauvage, F.; Reynaud, M.; Deschamps, M.; Bruyère, S.; Becuwe, M.; Postel, D.; Tarascon, J.-M.; Van Nhien, A. N.
Chem. Mater. 2015, 27, 7926-7933.
We report the physical and electrical characterization of a series of substituted imidazolium-based ionic liquids grafted on Stöber-type SiO2. This hybrid architecture affords an increase of the lithium transference to 0.56 by hindering TFSI? (bis(trifluoromethane)sulfonimide) mobility to the total ionic conductivity. When doped with 16 wt % wt LiTFSI, the resulting hybrid organic/inorganic solid material exhibits a lithium diffusion coefficient of 2 ? 10?12 m2/s at 87 °C and a conductivity of ca. 10?6 S/cm at room temperature and 10?4 S/cm at 65 °C with an activation energy barrier of 0.89 eV.

Selectivity of pyoverdine recognition by the FpvA receptor of Pseudomonas aeruginosa from molecular dynamics simulations
Bouvier, B.; Cezard, C.; Sonnet, P.
Phys. Chem. Chem. Phys. 2015, 17, 18022-18034.
The Gram-negative bacterium Pseudomonas aeruginosa, a ubiquitous human opportunistic pathogen, has developed resistances to multiple antibiotics. It uses its primary native siderophore, pyoverdine, to scavenge the iron essential to its growth in the outside medium and transport it back into its cytoplasm. The FpvA receptor on the bacterial outer membrane recognizes and internalizes pyoverdine bearing its iron payload, but can also bind pyoverdines from other Pseudomonads or synthetic analogues. Pyoverdine derivatives could therefore be used as vectors to deliver antibiotics into the bacterium. In this study, we use molecular dynamics and free energy calculations to characterize the mechanisms and thermodynamics of the recognition of the native pyoverdines of P. aeruginosa and P. fluorescens by FpvA. Based on these results, we delineate the features that pyoverdines with high affinity for FpvA should possess. In particular, we show that (i) the dynamics and interaction of the unbound pyoverdines with water should be optimized with equal care as the interface contacts in the complex with FpvA; (ii) the C-terminal extremity of the pyoverdine chain, which appears to play no role in the bound complex, is involved in the intermediate stages of recognition; and (iii) the length and cyclicity of the pyoverdine chain can be used to fine-tune the kinetics of the recognition mechanism.

Cyclodextrin nanoassemblies: a promising tool for drug delivery
Bonnet, V.; Gervaise, C.; Djedaïni-Pilard, F.; Furlan, A.; Sarazin, C.
Drug Discovery Today 2015, 20, 1120-1126.
Among the biodegradable and nontoxic compounds that can form nanoparticles for drug delivery, amphiphilic cyclodextrins are very promising. Apart from ionic cyclodextrins, which have been extensively studied and reviewed because of their application in gene delivery, our purpose is to provide a clear description of the supramolecular assemblies of nonionic amphiphilic cyclodextrins, which can form nanoassemblies for controlled drug release. Moreover, we focus on the relationship between their structure and physicochemical characteristics, which is crucial for self assembly and drug delivery. We also highlight the importance of the nanoparticle technology preparation for the stability and application of this nanodevice.

Alditol thiacrowns via a ring-closing metathesis of carbohydrate-derived α,ω-dithioallylethers
Benazza, M.; Danquigny, A.; Novogrocki, G.; Valgimigli, L.; Amorati, R.; Ferroni, F.; Demailly-Mullie, C.; Siriwardena, A.; Lesur, D.; Aubry, F.; Demailly, G.
Tetrahedron 2015, 71, 5602-5609.
We report a newly developed synthesis of a no. of alditol thiacrowns using an eco-friendly and versatile two-step strategy: the regioselective thioallyletherification of a polyhydroxylated alditol followed by a ring closing metathesis using the Grubbs second generation catalyst. This approach allows a series of target thiacrown products to be obtained in acceptable to good yields, from the corresponding α,ω-dithioallylether alditol starting materials featuring either the xylo, ribo, threo, erythro, D-manno or D-gluco configurations. The per-O-acetylated D-mannitol dithioallyether 10, easily obtained on a large scale using this approach, was selected for evaluation as both an antibacterial and an antioxidant. Although no antibacterial activity was obsd. for the bacterial strains investigated, compd. 10 is shown to be an antioxidant, and able to quench hydrogen peroxide in a stoichiometric fashion.

Cholesteryl and diosgenyl glycosteroids: synthesis and characterization of new smectic liquid crystals
Beaulieu, R.; Gottis, S.; Meyer, C.; Grand, E.; Deveaux, V.; Kovensky, J.; Stasik, I.
Carbohydr. Res. 2015, 404, 70-78.
While present in large numbers in nature, studies on the physical chemical aspects of glycosteroids are quite rare and focused on cholesterol, and all compounds studied thus far have shown liquid crystalline properties in a narrow temperature range. New glycosteroids composed by cholesterol or diosgenin and different glycosidic moieties have been synthesized here in order to analyze the influence of the structure on the formation of mesophases. These compounds have been studied by crossed polarized optical microscopy. These studies have revealed that these new glycosteroids form Smetic A liquid crystals in a broad temperature range.

Preparation of solanidine-derived glycosides and oligosaccharides as insecticides
Beaulieu, R.; Attoumbre, J.; Gobert-Deveaux, V.; Grand, E.; Stasik, I.; Kovensky, J.; Giordanengo, P.
2015, 56pp.; Chemical Indexing Equivalent to 162:219449 (FR).
The claimed synthesized solanidine derivs. I, where X = O or S and R1 = saccharidic or thiosaccharidic side-chain with 1-10 pentose and/or hexose units (esp. glucosyl, galactosyl and rhamnosyl units). The solanidine derivs. can be synthesized starting from the compd. II. Thus, glycoside I (X = O, R1 = β-glucopyranosyl) was prepd. and tested as insecticide agent against Macrosiphum euphorbiae. The compds. have toxic and/or repellent effects on aphids and other properties, including insecticidal, nematicidal, antiviral, antibacterial, and antifungal activities in agrochem. and pharmaceutical sense. The solanidine derivs. may be used as plant protective agents esp. against aphid pests.

Preparation of solanidine-derived glycosides and oligosaccharides as insecticides
Beaulieu, R.; Attoumbre, J.; Gobert-Deveaux, V.; Grand, E.; Stasik, I.; Kovensky, J.; Giordanengo, P.
2015, 56pp.; Chemical Indexing Equivalent to 162:219449 (FR).
The claimed synthesized solanidine derivs. I, where X = O or S and R1 = saccharidic or thiosaccharidic side-chain with 1-10 pentose and/or hexose units (esp. glucosyl, galactosyl and rhamnosyl units). The solanidine derivs. can be synthesized starting from the compd. II. Thus, glycoside I (X = O, R1 = β-glucopyranosyl) was prepd. and tested as insecticide agent against Macrosiphum euphorbiae. The compds. have toxic and/or repellent effects on aphids and other properties, including insecticidal, nematicidal, antiviral, antibacterial, and antifungal activities in agrochem. and pharmaceutical sense. The solanidine derivs. may be used as plant protective agents esp. against aphid pests.

Plasmon waveguide resonance for sensing glycan-lectin interactions
Alves, I.; Kurylo, I.; Coffinier, Y.; Siriwardena, A.; Zaitsev, V.; Harte, E.; Boukherroub, R.; Szunerits, S.
Anal. Chim. Acta 2015, 873, 71-9.
Carbohydrate-modified interfaces have been shown to be valuable tools for the study of protein-glycan recognition events. Label-free approache such as plasmonic based techniques are particularly attractive. This paper describes a new analytical platform for the sensitive and selective screening of carbohydrate-lectin interactions using plasmon waveguide resonance. Planar optical waveguides (POW), consisting of glass prisms coated with silver (50 nm) and silica (460 nm) layers were derivatized with mannose or lactose moieties. The specific association of the resulting interface with selected lectins was assessed by following the changes in its plasmonic response. The immobilization strategy investigated in this work is based on the formation of a covalent bond between propargyl-functionalized glycans and surface-linked azide groups via a Cu(I) "click" chemistry. Optimization of the surface architecture through the introduction of an oligo(ethylene glycol) spacer between the plasmonic surface and the glycan ligands provided an interface which allowed screening of glycan-lectin interactions in a highly selective manner. The limit of detection (LOD) of this method for this particular application was found to be in the subnanomolar range (0.5 nM), showing it to constitute a promising analytical platform for future development and use in a pharmaceutical or biomedical setting.