Glycocluster Tetrahydroxamic Acids Exhibiting Unprecedented Inhibition of Pseudomonas aeruginosa Biofilms

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 α-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 α-l-fucocluster (72%), but also with its α-d-manno (84%), and α-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

Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol

We studied the effect of several CDs on carvedilol’s solubility and chemical stability in various aqueous media. Our present results show that it is possible to achieve a carvedilol concentration of 5 mg/mL (12.3 mM) in the presence of 5 eq of γCD or RAMEB in an aqueous medium with an acceptable acid pH (between 3.5 and 4.7). Carvedilol formed 1:1 inclusion complexes but those with RAMEB appear to be stronger (K = 317 M−1 at 298 K) than that with γCD (K = 225 M−1 at 298 K). The complexation of carvedilol by RAMEB significantly increased the drug’s photochemical stability in aqueous solution. These results might constitute a first step towards the development of a novel oral formulation of carvedilol

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis

New cyclodextrin (CD)-grafted polymers functionalized with water-soluble phosphanes were synthesized in three steps starting from polyNAS. Once characterized by NMR spectroscopy and size-exclusion chromatography, they were used as additives in Rh-catalyzed hydroformylation of 1-hexadecene. The combined supramolecular and coordinating properties of these polymers allowed increasing the catalytic activity of the reaction without affecting the selectivities

Pseudomonas PA14H7: Identification and Quantification of the 7-Hydroxytropolone Iron Complex as an Active Metabolite against Dickeya, the Causal Agent of Blackleg on the Potato Plant

International audienceSoft rot Pectobacteriaceae (SRP), such as Pectobacterium and Dickeya, are phytopathogenic agents responsible for blackleg disease on several crops, such as potatoes, affecting the yield and depressing the seed production quality. However, neither conventional nor biocontrol products are available on the market to control this disease. In this study Pseudomonas PA14H7, a bacteria isolated from potato rhizosphere, was selected as a potential antagonist agent against Dickeya solani. In order to understand the mechanism involved in this antagonism, we managed to identify the main active molecule(s) produced by PA14H7. Cell-free supernatant (CFS) of PA14H7 cultures were extracted and analyzed using LC-MS, GC-MS, and NMR. We further correlated the biological activity against Dickeya solani of extracted CFS-PA14H7 to the presence of 7-hydroxytropolone (7-HT) complexed with iron. In a second time, we have synthesized this molecule and determined accurately using LC-UV, LC-MS, and GC-MS that, after 48 h incubation, PA14H7 released, in its CFS, around 9 mg/L of 7-HT. The biological activities of CFS-PA14H7 vs. synthetic 7-HT, at this concentration, were evaluated to have a similar bacteriostatic effect on the growth of Dickeya solani. Even if 7-HT is produced by other Pseudomonas species and is mostly known for its antibacterial and antifungal activities, this is the first description of its involvement as an effective molecule against pectinolytic bacteria. Our work opens the way for the comprehension of the mode of action of PA14H7 as a biocontrol agent against potato blackleg

Mass Spectrometry, Ion Mobility Separation and Molecular Modelling: A Powerful Combination for the Structural Characterisation of Substituted Cyclodextrins Mixtures

When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a complex isomers mixture of Lipidyl-βCDs (LipβCD) obtained with a degree of substitution 1 (DS = 1) from a one-step synthesis pathway. The benefit of tandem mass spectrometry (MS/MS) and ion mobility separation hyphenated with mass spectrometry (IM-MS) was investigated. The MS/MS fragment ion‘s relative intensities were analysed by principal component analysis (PCA) to discriminate isomers. The arrival time distribution (ATD) of each isomer was recorded using a travelling wave ion mobility (TWIM) cell allowing the determination of their respective experimental collision cross section (CCSexp). The comparison with the predicted theoretical CCS (CCSth) obtained from theoretical calculations propose a regioisomer assignment according to the βCD hydroxyl position (2, 3, or 6) involved in the reaction. These results were validated by extensive NMR structural analyses of pure isomers combined with molecular dynamics simulations. This innovative approach seems to be a promising tool to elucidate complex isomer mixtures such as substituted cyclodextrin derivatives

LiFSI vs. LiPF6electrolytes in contact with lithiated graphite:Comparing thermal stabilities and identification of specificSEI-reinforcing additives

International audienceLithium bis(fluorosulfonyl) imide (LiFSI) is regarded as an alternative to the classical LiPF6salt in today'sLiFePO4/graphite-based Li-ion batteries electrolyte owing to its slightly higher conductivity and lowerfluorine content. In an attempt to better evaluate the safety issues, here we report the comparative studyof the LiFSI and LiPF6based electrolyte/lithiated graphite interface thermal behavior. DSC measurementswith LiFSI-based electrolyte reveal a sharp exotherm with large heat release though at higher onsetand peak temperatures compared to LiPF6-based electrolyte. With the help of GC/MS,19F NMR and ESI-HRMS analyses, we assume that this highly energetic peak around 200◦C, which is dependant upon thelithium content, is mainly related to electrochemical reduction of FSI−anion. In a strategy to limit theprobability and damage of thermal runaway event, electrolyte additives such as vinylene carbonate (VC),fluoro ethylene carbonate (FEC), di-isocyanato hexane (DIH) and toluene di-isocyanate (TDI) have beeninvestigated and shown to significantly lower the energy associated with the exothermic phenomenon

A Combined Approach of NMR and Mass Spectrometry Techniques Applied to the α-Cyclodextrin/Moringin Complex for a Novel Bioactive Formulation †

Moringin, obtained via enzymatic conversion of the glucosinolate precursor glucomoringin, is an uncommon member of the isothiocyanate class, and has been proven to possess a broad range of biological activities such as antitumor activity, protection against neurodegenerative disorders and bactericidal effects. Since moringin is weakly soluble in water and unstable in aqueous medium, cyclodextrins (CDs) were considered for the development of a new moringin formulation, with a view to improving its solubility and stability in aqueous solution for use as an anti-inflammatory. A combined structural study using proton nuclear magnetic resonance (1H-NMR), diffusion-ordered spectroscopy (DOSY) and ion mobility mass spectrometry (IM-MS) is reported, highlighting the formation of a 1:1 α-CD/moringin inclusion complex. The association constant K was determined (1300 M−1 at 300 K). Completion of the structural characterization was performed by T-ROESY and MS/MS experiments, which evidenced the mode of penetration of moringin into α-CD. Finally, the “chaperone-like” properties of α-CD with respect to the stability of moringin have been highlighted

Non-targeted urinary metabolomic profiling for determination of metabolites associated with meat intake and the processes of meat cooking

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Thermal behaviour of the lithiated-graphite/electrolyte interface through GC/MS analysis

International audienceThe risk of thermal runaway is, for Li-ion batteries, a critical issue for large-scale applications. This compels manufacturers to find suitable materials or additives, which are able to minimize the heat generation and thereby mitigate safety-related risks. In an attempt to get more insight and understand the exothermic processes that take place at the negative electrode/electrolyte interface, we implemented GC/MS analytical technique to detect volatile compounds. Based on a mechanistic study, we propose a general electrolyte degradation scheme in the 100-250 ◦C temperature range, involving electrochemically driven carbonates reduction followed by chemical reactions. The mechanisms for decomposition deduced from these analyses shed new light on the processes involved in the formation of the precipitated (SEI layer) and soluble molecules upon cell formation cycles and ageing