Vincent Gerbaud

Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine.

Pancreatic juice is supersaturated with calcium carbonate. Calcite crystals therefore may occur, obstruct pancreatic ducts, and finally cause a lithiasis. Human lithostathine, a protein synthesized by the pancreas, inhibits the growth of calcite crystals by inducing a habit modification: the rhombohedral {10 1̄4} usual habit is transformed into a needle-like habit through the {112̄0} crystal form. A similar observation was made with the N-terminal undecapeptide (pE1R11) of lithostathine. We therefore aimed at discovering how peptides inhibit calcium salt crystal growth. We solved the complete x-ray structure of lithostathine, including the flexible N-terminal domain, at 1.3 Å. Docking studies of pE1R11 with the (101̄4) and (11 2̄0) faces through molecular dynamics simulation resulted in three successive steps. First, the undecapeptide progressively unfolded as it approached the calcite surface. Second, mobile lateral chains of amino acids made hydrogen bonds with the calcite surface. Last, electrostatic bonds between calcium ions and peptide bonds stabilized and anchored pE1R11 on the crystal surface. pE1R11-calcite interaction was stronger with the (11 2̄0) face than with the (10 1̄4) face, confirming earlier experimental observations. Energy contributions showed that the peptide backbone governed the binding more than did the lateral chains. The ability of peptides to inhibit crystal growth is therefore essentially based on backbone flexibility.

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 with 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. The 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-membered ring isomer (dioxane-type) is approximately 8 times more stable than the 5-membered 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.

Chemical enterprise model and decision-making framework for sustainable chemical product design

The chemical product substitution process is undertaken by chemical industries for complying with regulations, like REACH in Europe. Initially devoted to chemists, chemicals substitution is nowadays a complex process involving corporate, business and engineering stakeholders across the chemical enterprise for orienting the search toward a sustainable solution. We formalize a decision making process framework dedicated to the sustainable chemical product design activity in an industrial context. The framework aims at improving the sharing of information and knowledge and at enabling a collaborative work across the chemical enterprise stakeholders at the strategic, tactical and operational levels. It is supported by information and communication technologies (ICT) and integrates a computer aided molecular design tool. During the initial intelligence phase, a systemic analysis of the needs and usages enables to define the product requirements. In the design phase, they are compiled with the help of a facilitator to generate the input file of a computer aided product design tool. This multiobjective tool is designed to find mixtures with molecular fragments issued from renewable raw materials, and is able to handle environment-health and safety related properties along with process physicochemical properties. The final choice phase discusses the solution relevancy and provides feedback, before launching the product manufacturing. The framework is illustrated by the search of a bio-sourced water-solvent mixture formulation for lithographic blanket wash used in printing industry. The sustainability of the solution is assessed by using the sustainability shades method.

The structure of the agrochemical fungicidal 4-chloro-3-(3,5-dichlorophenyl)-1H-pyrazole (RPA 406194) and related compounds

Abstract The difficulties to obtain convenient monocrystals of the important fungicide RPA 406194 have been overcome by a combination of solid state 13C NMR, X-ray powder diffraction and molecular modeling. The compound, a 3-aryl tautomer, crystallizes forming infinite chains of molecules bonded by N–H⋯N hydrogen bonds, leading to needle-shaped crystals. The tautomerism (equilibrium constant and energy barrier) of this compound in solution has been studied.

Computer aided product design tool for sustainable product development

A computer aided product design (CAPD) tool is proposed that finds mixtures matching target properties. Genetic algorithm crossover and mutation operators are completed with insertion or deletion operators adapted for side branches. A new substitution operator is devised for cyclic molecules. The mixture fitness is evaluated by a weighted sum of property performances. Molecules are represented by molecular graphs. They are split into molecular fragments which are built from polyatomic groups. Molecules or molecular fragments can be fixed, constrained or left free for building a new molecule. Building blocks are chemical functional groups or bio-sourced synthons. A specific coding of hydrogen-suppressed atoms is devised that can be used with various property estimation models where atom connectivity information is required. Illustration is provided through three case studies to find levulinic, glycerol and bio-based derivatives as substitute for chlorinated paraffin, methyl p-coumarate ester solvent and blanket wash solvent, respectively.

Effect of stirring on the safety of flammable liquid mixtures

Flash point is the most important variable employed to characterize fire and explosion hazard of liquids. The models developed for predicting the flash point of partially miscible mixtures in the literature to date are all based on the assumption of liquid-liquid equilibrium. In real-world environments, however, the liquid-liquid equilibrium assumption does not always hold, such as the collection or accumulation of waste solvents without stirring, where complete stirring for a period of time is usually used to ensure the liquid phases being in equilibrium. This study investigated the effect of stirring on the flash-point behavior of binary partially miscible mixtures. Two series of partially miscible binary mixtures were employed to elucidate the effect of stirring. The first series was aqueous-organic mixtures, including water+1-butanol, water+2-butanol, water+isobutanol, water+1-pentanol, and water+octane; the second series was the mixtures of two flammable solvents, which included methanol+decane, methanol+2,2,4-trimethylpentane, and methanol+octane. Results reveal that for binary aqueous-organic solutions the flash-point values of unstirred mixtures were located between those of the completely stirred mixtures and those of the flammable component. Therefore, risk assessment could be done based on the flammable component flash-point value. However, for the assurance of safety, it is suggested to completely stir those mixtures before handling to reduce the risk.

Extractive distillation: recent advances in operation strategies

Abstract Extractive distillation is one of the efficient techniques for separating azeotropic and low-relative-volatility mixtures in various chemical industries. This paper first provides an overview of thermodynamic insight covering residue curve map analysis, the application of univolatility and unidistribution curves, and thermodynamic feasibility study. The pinch-point analysis method combining bifurcation shortcut presents another branch of study, and several achievements have been realized by the identification of possible product cut under the following key parameters: reflux ratio, reboil ratio, and entrainer-feed flow rate ratio. Process operation policies and strategy concerning batch extractive distillation processes are summarized in four operation steps. Several configurations and technological alternatives can be used when extractive distillation processes take place in a continuous or batch column, depending on the strategy selected for the recycle streams and for the main azeotropic feeds.

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.

An integrated framework for product formulation by computer aided mixture design

Abstract Computer-Aided Mixture Design using an evolutionary genetic algorithm was used to find substitutes to blanket wash solvent in lithographic printing process. Both molecular structure and composition of each molecule were run together as decision variables in order to find binary aqueous mixtures able to dissolve a phenolic resin. Bio-sourced molecular fragments were used as building blocks for generating potential solutions. Performance reached 0.96/1 using furoates and 0.95/1 using dioxolanes considering 12 desired physical properties in addition to the solvent power. Mixtures sourced from renewable material can match existing blanket wash in terms of solvent capabilities, while keeping other physical properties within target.

Chapter 6. Extractive distillation

The design and synthesis of extractive distillation rely upon the knowledge of residue curve map topology and the calculation of univolatility curves to analyze the volatility order of the mixture. Contrary to common belief, light, intermediate, heavy, and heterogeneous entrainers can be used to separate minimum- or maximum-boiling azeotropes and low-relative-volatility mixtures. After a preliminary selection of candidate entrainers based on selectivity and entrainer capacity, a general feasibility criterion enables one to find attainable products and suitable process configurations with the entrainer fed at a different location than the main mixture to be separated, inducing an extractive section within the column. It shows that the most or the least volatile component is recovered from a direct or an indirect split-column configuration in the distillate or in the bottom stream, respectively. Batch and continuous operations are governed by the same entrainer selection rules, but the operating parameter value ranges for the entrainer-feed flow rate ratio and the reflux ratio are different.