Indoloazepinone‐Constrained Oligomers as Cell‐Penetrating and Blood–Brain‐Barrier‐Permeating Compounds

Non‐cationic and amphipathic indoloazepinone‐constrained (Aia) oligomers have been synthesized as new vectors for intracellular delivery. The conformational preferences of the [l ‐Aia‐Xxx]_n oligomers were investigated by circular dichroism (CD) and NMR spectroscopy. Whereas Boc‐[l ‐Aia‐Gly]_2,4‐OBn oligomers 12 and 13 and Boc‐[l ‐Aia‐β³‐h‐l ‐Ala]_2,4‐OBn oligomers 16 and 17 were totally or partially disordered, Boc‐[l ‐Aia‐l ‐Ala]₂‐OBn ( 14 ) induced a typical turn stabilized by C₅‐ and C₇‐membered H‐bond pseudo‐cycles and aromatic interactions. Boc‐[l ‐Aia‐l ‐Ala]₄‐OBn ( 15 ) exhibited a unique structure with remarkable T‐shaped π‐stacking interactions involving the indole rings of the four l ‐Aia residues forming a dense hydrophobic cluster. All of the proposed FITC‐6‐Ahx‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers 19 – 23 , with the exception of FITC‐6‐Ahx‐[l ‐Aia‐Gly]₄‐NH₂ ( 18 ), were internalized by MDA‐MB‐231 cells with higher efficiency than the positive references penetratin and Arg₈. In parallel, the compounds of this series were successfully explored in an in vitro blood–brain barrier (BBB) permeation assay. Although no passive diffusion permeability was observed for any of the tested Ac‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers in the PAMPA model, Ac‐[l ‐Aia‐l ‐Arg]₄‐NH₂ ( 26 ) showed significant permeation in the in vitro cell‐based human model of the BBB, suggesting an active mechanism of cell penetration.     

Prediction of Power Consumption in a Mechanically Agitated Gassed Reactor in Viscous Batches

Volumetric mass transfer coefficient, power input, and gas holdup are key parameters in the design of mechanically agitated gas‐liquid contactors. Although the majority of industrial batches are of higher viscosity, reliable transport characteristics correlations for viscous batches are lacking in literature. These correlations are often based on the power input as the scale of energy dissipation. In order to develop reliable power input correlations, its measurements were carried out in a pilot‐plant vessel using multiple impellers of various types and diameters. Power input correlation shapes providing the best match with the comprehensive database are also expected to predict most precisely the impeller power in industrial‐scale vessels.     

Towards Diastereomeric Pure Salts with Antisolvent Methods

Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO₂, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.     

SkaSim – Skalierbare HPC‐Software für molekulare Simulationen in der chemischen Industrie

This article outlines advances in molecular modeling and simulation using massively parallel high‐performance computers (HPC). In the SkaSim project, partners from the HPC community collaborated with users from science and industry. The aim was to optimize the prediction of thermodynamic property data in terms of efficiency, quality and reliability using HPC methods. In this context, various topics were dealt with: atomistic simulation of homogeneous gas bubble formation, surface tension of classical fluids and ionic liquids, multicriteria optimization of molecular models, the development of the molecular simulation codes ls1 mardyn and ms2, atomistic simulation of gas separation processes, molecular membrane structure generators, transport resistors and the evaluation of predictive property data models based on specific mixture types.     

Assessment of k–ε models using tetrahedral grids to describe the turbulent flow field of a PBT impeller and validation through the PIV technique

In turbulence modeling, the RNG and Realizable models have important improvements in the turbulent production and dissipation terms in comparison to the Standard. The selection of the appropriate turbulence model has an impact on the convergence and solution in STRs, and they are used in mixing, multiphase modeling or as starting solution of transient models as DES and LES. Although there are several studies with the pitched blade turbine(PBT) impeller, most of them used the Standard model as representative of all k–ε models, using structured hexahedral grids composed of low number of cells, and in some cases under axial symmetry assumptions.Accordingly, in this work the assessment of the Standard, RNG and Realizable models to describe the turbulent flow field of this impeller, using the Multiple Reference Frame(MRF) and Sliding Mesh(SM) approaches with tetrahedral domains in dense grids, is presented. This kind of cell elements is especially suitable to reproduce complex geometries. Flow velocities and turbulent parameters were verified experimentally by PIV and torque measurements. The three models were capable of predicting fairly the pumping number, the power number based on torque, and velocities. Although the RNG improved the predictions of the turbulent kinetic energy and dissipation rate, the Realizable model presented better performance for both approaches. All models failed in the prediction of the total dissipation rate, and a dependence of its value on the number of cells for the MRF was found.     

Structural-microstructural characterization and optical properties of Eu3+,Tb3+-codoped LaPO4·nH2O and LaPO4 nanorods hydrothermally synthesized with microwaves

Rhabdophane-type Eu³⁺,Tb³⁺-codoped LaPO₄·nH₂O single-crystal nanorods with the compositions La_0.99999-xEu_xTb_0.00001PO₄·nH₂O (x?=?0–0.03), La_0.99999-yTb_yEu_0.00001PO₄·n′H₂O (y?=?0–0.010), and La_0.99999-zTb_zEu_0.000007PO₄·n′′H₂O (z?=?0–0.012) were hydrothermally synthesized with microwaves. It is shown that the Eu³⁺,Tb³⁺ codoping does not affect the thermal stability of these nanorods, which is due to the formation of substitutional solid solutions with both Eu³⁺ and Tb³⁺ replacing La³⁺ in the crystal lattice. Moreover, it is also shown that monazite-type Eu³⁺,Tb³⁺-codoped LaPO₄ single-crystal nanorods can be obtained by calcining their rhabdophane-type Eu³⁺,Tb³⁺-codoped LaPO₄·(n,n′ or n′′)H₂O counterparts at moderate temperature in air, and that they are thermally stable. It is also observed that, for the same Eu³⁺,Tb³⁺-codoping content, the monazite-type Eu³⁺,Tb³⁺-codoped LaPO₄ nanorods exhibit higher photoluminescent efficiency than the rhabdophane-type Eu³⁺,Tb³⁺-codoped LaPO₄· (n,n′ or n′′)H₂O nanorods. Moreover, it is found that the highest photoluminescence emission corresponds to the monazite-type La_0.96999Eu_0.02Tb_0.00001PO₄ nanorods for the La_0.99999-xEu_xTb_0.00001PO₄ system. However, for those compositions energy transfer from Tb³⁺ to Eu³⁺ does not occur. In addition, for an efficient energy transfer to occur, a content of at least 1?mol% Tb³⁺ is needed in all the studied materials.     

Effect of Zn addition on the structure and electrochemical properties of co-doped BaCe0.6Zr0.2Ln0.2O3-δ (Ln=Y,Gd, Yb) proton conductors

In this work, BaCe_0.6Zr_0.2Y_0.2-xYb_xO_3-δ and BaCe_0.6Zr_0.2Gd_0.2-xYb_xO_3-δ (x?=?0–0.20), proton conducting materials are prepared by the freeze-drying precursor method. The sintering conditions were optimized by adding Zn(NO₃)₂·6H₂O as sintering additive. The materials are thoroughly characterized by different structural and microstructural techniques, including X-ray diffraction, scanning and transmission electron microscopy, and thermogravimetric-differential thermal analysis. The addition of Zn favours the phase formation and densification at lower sintering temperatures; however, it leads to the segregation of a Zn-rich secondary phase, with general formula BaLn₂ZnO₅ (Ln?Y, Gd and Yb), which is identified and quantified for the first time. All samples with Zn as sintering aid exhibit cubic structure; however, the samples without Zn crystallize with orthorhombic or cubic structure, depending on the composition and thermal treatment. The electrical properties are studied by impedance spectroscopy. A deep analysis of the bulk and grain boundary contributions to the conductivity has revealed that the bulk conductivity remains almost unchanged along both series over Yb-doping; however, the grain boundary resistance decreases. The highest conductivity values are found for the intermediate members of both series, BaCe_0.6Zr_0.2Y_0.1Yb_0.1O_3-δ and BaCe_0.6Zr_0.2Gd_0.1Yb₁O_3-δ, with 33 and 28?mS?cm^?1 at 750?°C, respectively.     

Fenton and photo‐Fenton oxidation of a model mixture of dyes – overall kinetic analysis

The decolorisation and mineralisation of a model mixture of reactive dyes, under Fenton and photo‐Fenton conditions, have been investigated. A kinetic study was performed and rate constants and half‐life times determined from batch experimental data according to a pseudo‐first‐order degradation kinetic model. Moreover, the use of natural or artificial light, as well as the effect of temperature, was evaluated with the aim of finding the best Fenton process to promote the efficient degradation of the standard trichromatic system. The experimental results showed that the Fenton process run under solar light was the most effective. It is suggested that Fenton‐ and photo‐Fenton‐type reactions are viable techniques for the treatment of these types of dye mixtures, according to the high levels of colour, chemical oxygen demand and total organic carbon removal.