New 5-ylidene rhodanine derivatives based on the dispacamide A model.

International audienceA practical approach for the preparation of ([Formula: see text]) 5-ylidene rhodanine derivatives bearing the (4,5-dihalogeno-pyrrol-2-yl)carbamoyl fragment of dispacamide A is reported. The new compounds were obtained in good yields (19-88 %) by Knoevenagel condensation according to a solution-phase microwave dielectric heating protocol in the presence of organic bases (piperidine, TEA, and AcONa) from a set of [Formula: see text]-substituted rhodanines 2(a-i). The ten synthetic products 3(a-j) have been synthesized with a [Formula: see text]-geometry about their exocyclic double bond and the structure of one of these compounds (3) was confirmed by a single X-ray diffraction analysis. The new ([Formula: see text]) 5-ylidene rhodanine derivatives 3(a-j) were tested against eight protein kinases

An efficient approach to dispacamide A and its derivatives.

International audienceDispacamide A and new analogs of this marine alkaloid were prepared in seven steps with an overall yield ranging from 12 to 33%. The key step of the strategy was a stereocontrolled Knoevenagel condensation under microwave dielectric heating in the last step. In this condensation, the 2-aminoimidazolin-4-one hydrochloride partners 10a-c were synthesized in three steps with good overall yields (33-79%) via the ring closure of N-guanidino acetic acids 9a-c and the aldehydes 5a,b as the two others building-blocks, in 3 steps with 60-66% overall yields. The six synthetic products have been obtained with a Z geometry about their exocyclic bond on the basis of (13)C/(1)H long-range coupling constants using a gHSQMBC experiment

Impact of activated sludge acclimation on the biodegradation of toluene absorbed in a hydrophobic ionic liquid

International audienceClassical hydrophobic ionic liquids such as 3-butyl-1-methylimidazolium bis(trifluoroethylsulfonyl)imide or 3-butyl-1-methylimidazolium hexafluorophosphate application, as a non-aqueous liquid phase in a two-partitioning bioreactor to biodegrade hydrophobic volatile organic compounds by activated sludge, have been already reported in the literature, especially when the activated sludge was beforehand acclimated to the targeted volatile organic compound. In this study, four hydrophobic ionic liquids were used as non-aqueous liquid phase in a two-phase partitioning bioreactor to biodegrade toluene using non-acclimated activated sludge. The preliminarily results allowed to select two ionic liquids, 1-octylisoquinolinium bis(trifluoromethylsulfonyl)imide and allyl-diethylsulfonium bis(trifluoromethylsulfonyl)imide. The activated sludge was acclimated to both toluene and the considered ionic liquid. The results were compared to those obtained with non-acclimated activated sludge. The use of non-acclimated activated sludge for toluene biodegradation led to long lag times and low biodegradation rates. Thus, the acclimation to toluene improved the biodegradation rates; however, acclimation to both toluene and ionic liquid did not result in a significant improvement in the biodegradation rate compared to an acclimation to toluene alone. The activated sludge acclimation had a positive impact on toluene biodegradation and allowed to totally overcome the inhibitory effect of the presence of ionic liquid. The most relevant acclimation strategy seems to be a prior acclimation to toluene, whereas acclimation to the non-aqueous liquid phase can be achieved during the culture, namely by performing successive batches for instance, or a continuous operation. © 2017, Islamic Azad University (IAU)

Assessment of VOC absorption in hydrophobic ionic liquids: Measurement of partition and diffusion coefficients and simulation of a packed column

International audiencePartition coefficients of toluene and dichloromethane (DCM) in 23 hydrophobic ionic liquids (ILs), which can be used potentially for the physical absorption of volatile organic compounds (VOCs), were measured at 298 K. The partition coefficients, expressed as Henry’s law constants, were 400–1300 times for toluene and 10–47 times for DCM lower in the selected ILs than in water. Thus, the toluene and DCM diffusion coefficients were measured in three high potential hydrophobic ILs and in [Bmim][NTf2] using a thermogravimetric microbalance. Diffusivity measurements were performed at 298 K for toluene and between 278 and 308 K for DCM. Diffusion coefficients in ILs, ranging between 1 and 4 × 10−11 m2 s−1, were from 18 to 90 times lower than in water at 298 K. The diffusion coefficients were correlated to the temperature, the solute molar volume, the IL viscosity and molar volume with an average error of 4.2%. Finally, a 3 m industrial packed column was simulated for the removal of DCM and toluene in [AllylEt2S][NTf2] and [bmim][NTf2], which both present moderate viscosities of nearly 50 mPa s at 293 K. The overall mass-transfer coefficient, the removal efficiency and the pressure drop were calculated and compared to those obtained using other heavy solvents (a silicon oil and di-(2-ethylhexyl) adipate). This prospective simulation has demonstrated a good potential of ionic liquids for the toluene removal. Nonetheless, the DCM removal efficiencies simulated were lower than 44%. It suggests that even more efficient ionic liquids can be tuned and synthesized in the future for this specific application

Physicochemical properties of some hydrophobic room-temperature ionic liquids applied to volatile organic compounds biodegradation processes

International audienceBACKGROUNDIonic liquids (IL) are an interesting solvent choice for specific industrial applications since physicochemical properties can be fine-tuned by modifying the substituent groups or the cation/anion pair. Hydrophobic ILs are considered green solvents and known to be good absorbents for hydrophobic organic compounds. Given their physicochemical properties an industrial application of such compounds is conceivable. Classical physicochemical properties such as density, viscosity and surface tension have a strong influence on the fluid dynamics; they were therefore measured and determined. RESULTSThe density, viscosity and surface tension of 23 hydrophobic ILs were measured at room temperature. These compounds are potential candidates for the absorption and biodegradation of volatile organic compounds (VOCs) in a two-phase partitioning bioreactor. The thermal expansion coefficient, molecular volume, standard molar entropy and lattice energy were determined for each IL using empirical and semi-empirical equations based on the density values. Viscosity values were correlated by the Arrhenius equation. Then, the surface excess enthalpy and surface excess entropy were determined from the surface tension values. CONCLUSIONThe influence of the presence of different functional moieties (unsaturated bonding, oxygenated and cyanide) and the side chain length in the physicochemical properties of these hydrophobic ILs was discussed, since their presence affected directly the density, viscosity and surface tension

Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A

International audienceHere, we report on the synthesis of libraries of new 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones 3 (twenty-two compounds) and new 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones 5 (twenty-four compounds) with stereo controlled Z-geometry under microwave irradiation. The 46 designed final compounds were tested in order to determine their activity against four representative protein kinases (DYR1A, CK1, CDK5/p25, and GSK3α/β). Among these 1,3-thiazolidin-4-ones, the molecules (5Z) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC(50) 0.028 μM) and (5Z)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5H)-one 5s (IC(50) 0.033 μM) were identified as lead compounds and as new nanomolar DYRK1A inhibitors. Some of these compounds in the two libraries have been also evaluated for their in vitro inhibition of cell proliferation (Huh7 D12, Caco2, MDA-MB 231, HCT 116, PC3, and NCI-H2 tumor cell lines). These results will enable us to use the 1,3-thiazolidin-4-one core as pharmacophores to develop potent treatment for neurological or oncological disorders in which DYRK1A is fully involved

Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: design, synthesis, and validation.

International audienceIron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex