Effect of fluorination and size of the alkyl side-chain on the solubility of carbon dioxide in 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ionic liquids.

It is proven in this work that it is possible to significantly increase the carbon dioxide uptake by an ionic liquid relying on physical interactions only. The solubility and thermodynamics of solvation of carbon dioxide in the ionic liquids 1-octyl-3-methylimidazolium bis[trifluoromethylsulfonyl]amide [C(8)mim][Ntf(2)], 1-decyl-3-methylimidazolium bis[trifluoromethylsulfonyl]amide [C(10)mim][Ntf(2)], and 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[trifluoromethylsulfonyl]amide [C(8)H(4)F(13)mim][Ntf(2)] were determined experimentally between 298 and 343 K at pressures close to atmospheric. The solubility of carbon dioxide is significantly higher in the fluorine-substituted ionic liquid with Henry's law constants at 303 K of 33.3 and 30.7 bar for [C(8)mim][Ntf(2)] and [C(10)mim][Ntf(2)], respectively, and of 28.0 bar for [C(8)H(4)F(13)mim][Ntf(2)]. Molecular simulation was used for interpreting the molecular mechanisms of solvation of carbon dioxide in the studied ionic liquids and coherent molecular mechanisms of solvation are proposed in light of the solute-solvent radial distribution functions. It is shown that the increase of the size of the hydrogenated or fluorinated alkyl chain in the imidazolium cation does not lead to a steady augmentation of the gaseous uptake by the liquid probably due to an increase of the nonpolar domains of the ionic liquid, carbon dioxide being solvated preferentially in the charged regions of the solvent.

Deoxysugars via microbial reduction of 5-acyl-isoxazolines: application to the synthesis of 3-deoxy-D-fructose and derivatives.

5-Acylisoxazolines 3a-d were obtained by 1,3-dipolar cycloaddition from acetoxymethyl vinyl ketone and nitro precursors. Compounds 3a-d were biotransformed by Aspergillus niger into a 1:1 mixture of stereomers of 5-dihydroxyethyl isoxazolines (+)-4a-d (anti) and (-)-5a-d (syn). Both stereomers were obtained in good yields and with high optical purities. Carbonyl reduction by Aspergillus niger produces alcohols of R-configuration thus giving an access to D-sugar analogues: Compound (+)-4d was converted to 3-deoxy-D-erythro-hexulose and several protected derivatives. Total synthesis of 3-deoxy-D-fructose-6-phosphate was also achieved in two steps and 64% overall yield from (+)-4d.

Asp477 is a determinant of the enantioselectivity in yeast transketolase.

The conserved residue Asp477 in yeast transketolase is located in the substrate channel of the enzyme and forms a hydrogen bond with the C2-hydroxyl group of the acceptor substrate. The significance of this interaction for the recognition of the preferred acceptor substrates, D-alpha-hydroxyaldehydes was investigated by site-directed mutagenesis. In the wild-type enzyme the kcat/KM values are by three to four orders of magnitude lower for 2-deoxyaldoses or substrates with L-configuration at the C2-atom. In the Asp477 Ala mutant, the kcat/KM values for D-alpha-hydroxyaldehydes are decreased by a thousandfold, while the kcat/KM values for substrates with L-configuration or 2-deoxyaldoses are similar to wild-type enzyme. These results indicate that Asp477 is involved in determining the enantioselectivity of transketolase.

Slow reversible inhibitions of rabbit muscle aldolase with substrate analogues: synthesis, enzymatic kinetics and UV difference spectroscopy studies.

Various dihydroxyacetone-phosphate (DHAP) analogues bearing an aromatic ring or beta-dicarbonyl structures were synthesized. Their capacity to form a stabilized iminium ion or conjugated enamine in the reaction catalyzed by rabbit muscle aldolase (EC 4.1.2.13) were investigated by enzymatic kinetics and UV difference spectroscopic techniques. Whereas the aromatic derivative led to competitive inhibition without detectable iminium ion formation, slow reversible inhibitions of aldolase by beta-dicarbonyl compounds was shown to have taken place. Conjugated enamine formation at the active site of the enzyme was detected by their specific absorbances close to 317 nm.

Effects of chirality and substituents at carbon 3 in dihydroxyacetone-phosphate analogues on their binding to rabbit muscle aldolase.

A series of dihydroxyacetone-phosphate (DHAP) analogues has been synthesized, differing in their stereochemistry and functionality at C-3. The kinetic effects of these compounds on the enzyme aldolase (EC 4.1.2.13) have been studied and differing modes of action observed. Competitive and time dependent reversible inhibition have been shown to take place both with and without borohydride detected formation of an immonium ion.

[Rational concepts and the study of active molecules against various trypanosomiases]. / Conception rationnelle et étude de molécules actives contre les différentes trypanosomiases.

Several sets of compounds, active against different trypanosomes, Trypanosoma brucei and Trypanosoma cruzi are presented, the lethal doses for some of them being less than the micro-molar concentration. These compounds are designed by taking advantage of two metabolic features of these parasites, glucose metabolism and oxidative stress.

Inhibition of the glycolytic enzymes in the trypanosome: an approach in the development of new leads in the therapy of parasitic diseases.

Glycolysis in the trypanosome represents an important target for the development of new therapeutic agents due to the fact that this metabolism is essential for the parasite, glucose being its sole source of energy. In addition, different features of this metabolism and those associated with glycolytic enzymes offer opportunities for the development of efficient and selective compounds. Examples are given in this work of inhibitors directed to the enzymes aldolase and glyceraldehyde-phosphate-dehydrogenase and also of molecules acting specifically on the clusters of basic amino-acids present at the surfaces of the glycolytic enzymes in the parasite.