A “top-down” in silico approach for designing ad hoc bio-based solvents: application to glycerol-derived solvents of nitrocellulose

Potentially effective glycerol-based solvents for nitrocellulose have been designed using a top-down in silico procedure that combines Computer Assisted Organic Synthesis (CAOS) and Molecular Design (CAMD). Starting from a bio-based building block – glycerol – a large number of synthetically feasible chemical structures have been designed using the GRASS (GeneratoR of Agro-based Sustainable Solvents) program. GRASS applies well-selected industrial chemical transformations to glycerol together with a limited number of relevant co-reactants. Then, the most promising structures are considered as lead compounds for further modification in silico thanks to the IBSS (InBioSynSolv) program, which generates derivatives with alkyl, cycloalkyl, alkene, cycloalkene or phenyl substituents. Finally, IBSS ranks all the candidates according to the value of their overall performance function to best fit the predefined specifications, i.e. (i) high solubilisation of nitrocellulose, (ii) slow evaporation and non-flammability (iii) low toxicity and environmental impact. This general strategy enables the highlighting of the most relevant solvent candidate derived from any building block for a given application. To validate the approach, 15 commercially available solvents derived from glycerol were confronted with nitrocellulose and led to highlight diacetin as an effective and safe solvent

The Cost of Cochlear Implantation: A Review of Methodological Considerations

Objectives. Cost studies can provide useful guidance, so long as they adhere to accepted methodology. Cochlear implants (CIs) are electronic devices introduced surgically into the inner ear. It is a relevant example to review cost study analyses because of its costliness. The aim of this study was to review relevant published cost studies of CI to analyze the method used. Methods. First, we described the key points of cost study methodology. Cost studies relating to CI were systematically reviewed, focussing on an analysis of the different methods used. Results. The methods, data sources, and estimated cost categories in each study varied widely. The paper showed that cost studies adopted significantly different approaches to estimate costs of CI, reflecting a lack of consensus on the methodology of cost studies. Conclusion. To increase its credibility, closer agreement among researchers on the methodological principles of cost studies would be desirable

Glycerol Acetals and Ketals as Bio-based Solvents: Positioning in Hansen and COSMO-RS spaces, Volatility and Stability towards Hydrolysis and Autoxidation

Four recently launched cyclic glycerol acetals or ketals are evaluated as bio-based solvents. Three of them are industrially available and result from the condensation of glycerol with formaldehyde, acetone and isobutyl methyl ketone. The fourth is under development and is prepared by the reaction of glycerol with benzaldehyde under heterogeneous acidic catalysis. Their solvent properties are evaluated through Hansen and COSMO-RS (COnductor-like Screening MOdel for Real Solvents) approaches, in comparison to traditional petrochemical solvents. Dioxolane- and dioxane-type isomers have close solubility parameters; however the nature of the starting aldehyde/ketone significantly impacts the solvency properties. Stability to hydrolysis depends heavily on both the aldehyde/ketone part and on the size of the ring. In acidic medium, acetals are found to be more stable than ketals and glycerol-based ketals are more stable than ethylene glycol-based ketals. In the case of benzaldehyde glycerol acetal, it is shown that the 6-member ring isomer (dioxane-type) is approximately 8 times more stable than the 5-member ring counterpart (dioxolane-type) at low pH. Stability towards autoxidation by O2 is high for formaldehyde and acetone-derived acetals and drops for the other two compounds. Glycerol acetals and ketals are promising potential alternatives to some harmful solvents such as glycol ethers and aniline

Les noms composés incluant un terme de couleur

TOULOUSE2-BUC Mirail (315552102) / SudocSudocFranceF

Etudes des relations structure-propriétés d'esters gras de saccharose (synthèse, propriétés en solution par PGSE RMN et comportement cristal liquide thermotrope)

Une des voies actuelles de valorisation chimique du saccharose, la molécule organique pure la plus produite dans le monde, est la production d'esters gras tensioactifs. Principalement utilisés comme émulsifiants alimentaires, les sucroesters sont constitués d'un mélange d'espèces mono et polysubstituées et de différents régioisomères, ce qui rend difficile la rationalisation de leurs propriétés physico-chimiques. Le travail présenté vise à établir les liens entre propriétés et structure, au niveau moléculaire, par l'étude d'esters de saccharose définis. Pour cela, différents types de catalyse, chimique et enzymatique, ont permis d'atteindre diverses positions d'acylation et de contrôler le degré de substitution. La mesure de coefficients d'auto-diffusion en solution par RMN et l'étude du comportement cristal liquide thermotrope ont mis en évidence des différences notables de comportement entre les dérivés préparés, en fonction de la position d'acylation et de la nature de la chaîne.LYON1-BU.Sciences (692662101) / SudocSudocFranceF

An Overview of l-Amino Acid Oxidase Functions from Bacteria to Mammals: Focus on the Immunoregulatory Phenylalanine Oxidase IL4I1

l-amino acid oxidases are flavin adenine dinucleotide-dependent enzymes present in all major kingdom of life, from bacteria to mammals. They participate in defense mechanisms by limiting the growth of most bacteria and parasites. A few mammalian LAAOs have been described, of which the enzyme “interleukin-4 induced gene 1” (IL4I1) is the best characterized. IL4I1 mainly oxidizes l-phenylalanine. It is a secreted enzyme physiologically produced by antigen presenting cells of the myeloid and B cell lineages and T helper type (Th) 17 cells. Important roles of IL4I1 in the fine control of the adaptive immune response in mice and humans have emerged during the last few years. Indeed, IL4I1 inhibits T cell proliferation and cytokine production and facilitates naïve CD4+ T-cell differentiation into regulatory T cells in vitro by limiting the capacity of T lymphocytes to respond to clonal receptor stimulation. It may also play a role in controlling the germinal center reaction for antibody production and limiting Th1 and Th17 responses. IL4I1 is expressed in tumor-associated macrophages of most human cancers and in some tumor cell types. Such expression, associated with its capacity to facilitate tumor growth by inhibiting the anti-tumor T-cell response, makes IL4I1 a new potential druggable target in the field of immunomodulation in cancer

Editorial: Immunosuppressive Amino Acid Catabolizing Enzymes in Heallth and Disease

International audienc

Conception, modélisation et caractérisation de solvants agro-sourcés

Le bouleversement du monde des solvants classiques, résultant de la récente prise de conscience des risques environnementaux et sanitaires liés à leur utilisation, a conduit au développement de nouveaux solvants présentant un meilleur profil HSE et dérivés de la biomasse végétale : les agro-solvants. Ces solvants alternatifs ont été recensés, modélisés et comparés aux solvants organiques classiques dans un panorama purement théorique établi grâce à l'approche COSMO-RS. Cet outil permet non seulement d'aider à la substitution de solvants indésirables mais aussi de souligner les besoins de nouvelles structures. Une démarche in silico de conception raisonnée d'agro-solvants, via le développement d'un logiciel de synthèse automatique, GRASS, a ainsi été mise en place et permet de générer virtuellement des produits de commodités à partir d'agro-synthons abondants (glycérol, acide itaconique, isosorbide, etc.) et de transformations chimiques pertinentes industriellement. Les structures générées sont ensuite triées via des modèles de prédiction de propriétés physico-chimiques afin de sélectionner les mieux adaptés pour une application donnée. Des agro-solvants dérivés du glycérol et de l'isosorbide (éthers, esters, acétals) ont été sélectionnés, synthétisés puis évalués expérimentalement en considérant leurs propriétés physico-chimiques (Tfus, Téb, d, , stabilités à l'hydrolyse et à l'oxydation), leurs capacités de solubilisation de deux pesticides cibles et leurs propriétés hydrotropes. Ces mesures expérimentales ont ensuite été confrontées à différents modèles de prédiction.Many of the traditional organic solvents (halogenated compounds, aromatics, glycols ethers) are banned or about to be, as a result of the recent awareness of the environmental and health risks associated with their use. There is therefore an urgent need to find alternatives with good ESH (Environment, Safety and Health) profiles, preferably coming from renewable feedstock: the so-called biosolvents. In this work, these alternative solvents have been listed, modeled, and compared to classical organic ones to give a purely predictive landscape obtained thanks to the COSMO-RS approach. This tool can be used to help in finding substitution solutions and also highlights the needs for new biosolvents. A Computer-Assisted Organic Synthesis program, named GRASS, has been developed to help in the rational design of biosolvents from a bio-based building block (glycerol, itaconic acid, isosorbide, etc.) through industrially-relevant chemical transformations. Then, all the virtual derivatives generated have been sorted out thanks to property prediction models in order to select the most relevant ones. Biosolvents coming from glycerol and isosorbide (ethers, esters, acetals) have been selected, synthesized and experimentally evaluated as solvents considering their physico-chemical properties (m.p., b.p., d, , stabilities to hydrolysis and to oxidation), their capacities to solubilise two agrochemicals, and their hydrotropic properties. These experimental data have then been compared to various prediction models.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

Revisiting the phase inversion temperature as a practical tool for EOR applications

National audienc