β-Cyclodextrins grafted with chiral amino acids: A promising supramolecular stabilizer of nanoparticles for asymmetric hydrogenation?

International audienceWater-soluble ruthenium nanoparticles stabilized by randomly methylated β-cyclodextrins (RaMeCDs) grafted with chiral amino-acid moieties like l-alanine (Ala) and l-leucine (Leu) were prepared in aqueous solution by two approaches: (i) a one-step hydrogen reduction of ruthenium trichloride as metal source in the presence of appropriate cyclodextrins (one-pot method) or (ii) a NaBH4 reduction of the metal salts, followed by the stabilization of ruthenium hydrosol by the addition of chirally modified RaMeCDs (cascade method). The influence of the ligand's nature and the synthesis methodologies on the size, dispersion and surface properties of the obtained ruthenium colloids were studied by TEM and NMR analyses. The spherical ruthenium suspensions contain very small particles (0.82-1.00 nm) with narrow size distributions. Their catalytic properties were evaluated in biphasic hydrogenation of various prochiral compounds (olefins, ketones and disubstituted arenes) showing promising results in terms of activity and selectivity. Nevertheless, no significant enantiomeric excesses were observed

Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy

International audienceBACKGROUND: This study was designed to evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ).METHODS: This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and (1)H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results.RESULTS: A total of 21 LGGs from 31 patients were included in the study, and followed for at least n=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated over time (Spearman ρ=+0.95) and followed a logarithmic regression (P>0.001). The evolutions over time of metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(ΔV(n)/V(o)), according to a linear regression (P<0.001) in the 'response/no relapse' patient group, and with the evolution of the mean tumour volume (meanV(n)), according to an exponential regression (P<0.001) in the 'response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(Cho/Cr)(n)/(Cho/Cr)(o)), at n=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((Cho/NAA)(n)-(Cho/Cr)(n))/(Cho/NAA)(n), at n=4 months was predictive of tumour relapse with a significant cutoff of 0.046, a sensitivity of 60% and a specificity of 100% (P=0.004).CONCLUSIONS: The (1)H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, (1)H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ

Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based Fatty Acid Amide Guanidines: Effect on Gene Silencing Efficiency

Four guanidine derivatives of N4,N9-diacylated spermine have been designed, synthesized, and characterized. These guanidine-containing cationic lipids bound siRNA and formed nanoparticles. Two cationic lipids with C18 unsaturated chains, N1,N12-diamidino-N4,N9-dioleoylspermine and N1,N12-diamidino-N4-linoleoyl-N9-oleoylspermine, were more efficient in terms of GFP expression reduction compared to the other cationic lipids with shorter C12 (12:0) and very long C22 (22:1) chains. N1,N12-Diamidino-N4-linoleoyl-N9-oleoylspermine siRNA lipoplexes resulted in GFP reduction (26%) in the presence of serum, and cell viability (64%). These data are comparable to those obtained with TransIT TKO. Thus, cationic lipid guanidines based on N4,N9-diacylated spermines are good candidates for non-viral delivery of siRNA to HeLa cells using self-assembled lipoplexes

Chimie supramoléculaire et mécanochimie : de la modification sélective des cyclodextrines à la catalyse en phase solide

National audienc

Influence de la chimie sur l'environnement : du constat à l'action !

National audienc

Cyclodextrines et mécanochimie : de la synthèse à la catalyse

National audienc

Extension de la réaction phosphine imide en série cyclodextrine (Synthèses et propriétés de nouvelles cyclodextrines complexantes)

Dans le développement de nouvelles synthèses, le remplacement des composés volatils organiques tels que les réactifs industriels dangereux apparaît comme important. C est aujourd'hui le défi de la chimie verte. La réaction Phosphine imide rend facile d accès certaines fonctions quadrivalentes tel que isocyanate, carbodiimide, thio-urée ou urée notamment dans des CDs. Nous avons pu démontré la sûreté, l'efficacité et la polyvalence de cette réaction avec PPH3 libre ou supporté sur polymère avec CS2, CO2 et le CO2 supercritique. Dans la deuxième partie, les propriétés physico-chimique de coordination sélective de cations métalliques et certaines propriétés de fluorescence des complexes de terre rare d'ureido-CDs ont été étudiées. Ces nouveaux systèmes se sont avérés être très sélectifs et originaux , notamment dans la coordination avec la série de lanthanide. Pour la dernière partie, la synthèse d un récepteur C2 symétrique comprenant deux CDs reliés par des liens urée à une plate-forme chirale diaza-éther-couronne est rapportée. Ce système moléculaire s'est avéré un outil efficace de complexation du Busulfan, un agent anticancéreux utilisé pour le traitement des maladie hématologiques. Enfin, un tétrapode de bis-guanidinum , premier membre d'une nouvelle famille à centres cationiques et quantité de CDs modulable est présenté. La complexation de nucléotides avec cette structure a été étudié. On observe la formation du complexe bimoléculaire combinant des inclusions dans les cavités des hydrophobes des CDs et des interactions électrostatiques entre le guanidinium et les anion phosphate.In the development of new efficient synthetic processes, the replacement of organic volatile compounds such as hazardous industrial reagents appears as a major gaol in the present day challenge for a green chemistry. It is well know that compounds containing the urea or thiourea functionality are of extended biological. As a powerful easy access to urea functionality and other main quatrivalent functions of chemistry as eg isocyanates, carbodiimide, thiourea or urea notably in CDs series, we earlier reported and demonstrated the high safety, efficiency and versatility of the phosphine imide reaction with free or polymer supported PPH3 and with CS2, CO2 or supercritical CO2. On the second part, specific physico-chemical property related to selective metal coordination and to fluorescence properties of URTF ureido-CDs rare earth complexes were investigated. This new systems were found to have very selective and original coordination processes notably with lanthanide series. For the last part, the synthesis of C2 symmetric receptor including two CDs connected by urea linkers to the chiral diazacrown ether o platform is reported. This molecular system was found to be an efficient complexion tool towards the Busulfan anticancer agent used for the treatment of haematological disorders. A novel bis-guanidinum tetrapode, the first member of a new host family with a checked number of cationic centres and CDs is presented. Its molecular recognition towards nucleodides guest was investigated. The formation of ditopic bimolecular complexe was observed combining host-guest hydrophobic inclusion into CDs and electrostatic interactions between guanidinium and phosphate anion.NANCY1-SCD Sciences & Techniques (545782101) / SudocSudocFranceF

From selective modification to catalysis in solid phase: Interest of mechanochemical activation in cyclodextrins’ chemistry

International audienc

Vers la précision inframillimétrique en IRM en conditions stéréotaxiques (application au traitement par stimulation profonde de la maladie de Parkinson)

A l heure actuelle, il y a un développement considérable des techniques de neurostimulation qui sont à l'origine d'une révolution thérapeutique dans le traitement de la maladie de Parkinson. Ces méthodes nécessitent une imagerie cérébrale très précise qui ne peut être obtenue qu'en IRM. Cependant, certains recourent encore à la ventriculographie à cause du risque de distorsions en IRM. Pour palier aux problèmes de distorsions sur les acquisitions stéréotaxiques pondérées en T1 et T2, nous avons développé une méthode d analyse des distorsions à partir d un fantôme dédié. L acquisition T1 présente des distorsions de faibles amplitudes, homogènes dans tout le volume. Contrairement, l analyse de l acquisition T2 montre de sévères distorsions dans les trois directions de l espace produisant un décalage de plusieurs voxel. A partir de cette analyse, nous avons établi une méthode de correction basée sur un volume de vecteurs de déplacement. La méthode de correction a réduit les distorsions inférieures au millimètre sur les acquisitions T2. La correction a été également appliquée sur une série d acquisition de patients parkinsoniens. L acquisition T1 (non distordue) a servi de volume de référence pour quantifier les résultats. Après recalage des images T2 sur le T1, nous avons mesuré différentes structures anatomiques et constaté que chacune des mesures effectuées après correction sur le T2 convergeaient vers celles obtenues en T1. Ainsi, la méthode de correction des distorsions permet de réduire significativement les distorsions sur les images du fantôme et des patients. Elle permettra de pouvoir repérer avec précision les structures anatomiques par recalage sur le T1.High-frequency stimulation of the subthalamic nucleus (STN) is an effective method for treating refractory idiopathic Parkinson disease (PD). MRI in stereotactic conditions is used by many teams to perform pre-operative targeting of the STN. The goal of this study is to analyze and correct the geometric observed on MR acquisitions used for targeting of the STN. Dedicated phantom of known geometry was used. We calculated existing shifts between measured points and theoretically defined points on the same T1 and T2-weighted sequences used to target STN. A shifting volume was built to correct the distorsion. A quantitative study of the correction was carried out on the phantom images and acquisitions done in patients. To quantify the distortion corrections in patients, we evaluated different anatomical structure. Results show that the distortions are greater in T2 and weak in T1-weighted acquisitions, of the size order of one pixel. The geometric distortion was significantly reduced and smaller than pixel size after distortion correction. Study of the patient s scans showed a good correspondence between anatomical structure in T1 (not distorted) and T2 corrected. The MR distortions observed on a T1-weighted acquisition remains very low, this confirms that this type of sequence can be used with stereotactic precision,.T2-weighted acquisition can be used to obtain measurement at the center part of the field of view but cannot be used directly for stereotactic targets determination. Correction of the geometrical distortion observed on the T2-weighted sequence can be obtained with our method and could be used to the stereotactic procedure.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF