Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase

Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E = 52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E ? 300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E ? 300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E ? 300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5 times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters.     

Synthesis of EMT/FAU-type zeolite nanocrystal aggregates in high yield and crystalline form

This work focuses on different ways to improve the yield and/or the crystalline quality of EMT/FAU-type zeolite nanocrystal aggregates obtained in the presence of organic additive triethanolamine (TEA). The increase of the amount of aluminum reagent enhances the synthesis yield by a factor of 2.5 without affecting the crystallization rate and the microporous volume. On the other hand, the increase of the thermal treatment time allows to increase the synthesis yield, the crystallization rate and the microporous volume. Furthermore, addition of EMT zeolite seeds into the starting reaction medium improves the crystallization rate and the microporous volume.     

Limonene as an agro-chemical building block for the synthesis and extraction of bioactive compounds

The objective of this study was to transform limonene as an agro-chemical platform for the production of a wide range of added-value compounds for pharmaceutical, cosmetic and food ingredients. This molecule was also evaluated as an alternative solvent for the extraction of several bioactive compounds compared to n-hexane. Limonene was extracted from the essential oils of orange peels through a solvent-free microwave extraction technique. Limonene was successfully transformed into products with industrial interest by catalytic oxidation using three different iron catalysts. The ability of limonene to be used as an alternative solvent was performed using two simulation tools, Hansen solubility parameters (HSPs) and the Conductor-like Screening Model for Real Solvents (COSMO-RS), and via experimentation. The results indicated that limonene could be a promising green solvent and synthon for petroleum substitution in the extraction or synthesis of bioactive compounds.     

Motion of a porous sphere in a spherical container

The creeping motion of a porous sphere at the instant it passes the center of a spherical container has been investigated. The Brinkman's model for the flow inside the porous sphere and the Stokes equation for the flow in the spherical container were used to study the motion. The stream function (and thus the velocity) and pressure (both for the flow inside the porous sphere and inside the spherical container) are calculated. The drag force experienced by the porous spherical particle and wall correction factor is determined. To cite this article: D. Srinivasacharya, C. R. Mecanique 333 (2005).     

ADER discontinuous Galerkin schemes for aeroacoustics

In this paper we apply the ADER approach to the Discontinuous Galerkin (DG) framework for the two-dimensional linearized Euler equations. The result is an efficient high order accurate single-step scheme in time which uses less storage than Runge–Kutta DG schemes, especially for very high order of accuracy. The aim is to obtain an arbitrarily accurate scheme in space and time on unstructured grids for accurate noise propagation in the time domain in very complex geometries. We will present numerical convergence rates for ADER-DG methods up to 10th order of accuracy in space and time on structured and unstructured meshes. To cite this article: M. Dumbser, C.-D. Munz, C. R. Mecanique 333 (2005).     

Second-order estimates for the large-deformation response of particle-reinforced rubbersEstimations homogénéisées pour le comportement mécanique des caoutchoucs renforcés en grandes déformations

This paper presents the application of a recently proposed ‘second-order’ homogenization method (J. Mech. Phys. Solids 50 (2002) 737–757) to the estimation of the effective behavior of hyperelastic composites subjected to finite deformations. The main feature of the method is the use of ‘generalized’ secant moduli that depend not only on the phases averages of the fields, but also on the phase covariance tensors. The use of the method is illustrated in the context of particle-, or fiber-reinforced elastomers and estimates analogous to the well-known Hashin–Shtrikman estimates for linear-elastic composites are generated. The new estimates improve on earlier estimates (J. Mech. Phys. Solids 48 (2000) 1389–1411) neglecting the use of fluctuations. In particular, the new estimates, unlike the earlier ones, are capable of recovering the exact incompressibility constraint when the matrix is also taken to be incompressible. To cite this article: O. Lopez-Pamies, P. Ponte Castañeda, C. R. Mecanique 331 (2003).     

Calcul à la rupture en présence d'un écoulement à surface libre : construction de champs de pression approchésYield design for porous media subjected to unconfined flow: construction of approximate pressure fields

We consider the stability of a porous medium submitted to a steady-state flow with free-boundary. Assuming some hypotheses, it is possible to implement the kinematic method by using an approximate pressure field bounding the true pressure field from below. We are interested in finding such approximate pressure fields and in proving that they bound the true pressure field from below without knowing the true pressure field. We use fields which are solutions of a problem with relaxed conditions with regard to the real problem. Under a uniqueness condition of the solution of a weak formulation of the problem, such fields are lower bounds for the true pressure field. Finally, we give the example of a vertical dam. To cite this article: A. Corfdir, C. R. Mecanique 334 (2006).     

On the slow motion of a cluster of bubbles under the combined action of gravity and thermocapillarity

The slow migration of N spherical bubbles under combined buoyancy and thermocapillarity effects is investigated by appealing solely to $3N+1$ boundary-integral equations. In addition to the theory and the associated implementation strategy, preliminary numerical results are both presented and discussed for a few clusters involving 2, 3, 4 or 5 bubbles with a special attention paid to the case of rigid configurations. To cite this article: A. Sellier, C. R. Mecanique 333 (2005).     

Modified fixed point algorithm in fluid–structure interactionAccélération avec des conditions de transpiration d'un algorithme de point fixe en interaction fluide–structure

In this work, we address the numerical solution of some non-linear problems arising in the time discretization of fluid–structure interaction problems with fully implicit schemes. At each time step, we have to solve a highly non-linear coupled system, since the fluid domain depends on the unknown displacement of the structure. We propose a modified fixed-point algorithm which combines the Block-Gauss–Seidel iterations with a transpiration formulation. Numerical experiments show the great improvement in computing time with respect to the standard method. To cite this article: S. Deparis et al., C. R. Mecanique 331 (2003).