The binding mode of progesterone to its receptor deduced from molecular dynamics simulations

An unambiguous understanding of the binding mode of human progesterone to its receptor still eludes experimental search. According to the X-ray structure of the ligand-binding domain, only one (O3) of the two keto groups at the ligand ends (O3 and O20) should play a role. This result is in conflict with chemical intuition and the results of site-directed mutagenesis experiments. Herein, we report classical molecular dynamics simulations that reveal the dynamic nature of the binding in solution, elucidate the reasons why X-ray studies failed to determine the role of O20, and clarify the effects of the mutations. The predictive power of the force field is ensured by the consistent introduction of a first-principles representation of the ligand.     

1H nuclear magnetic resonance study of polyurethane prepolymers from toluene diisocyanate and polypropylene glycol

Polyurethane prepolymers prepared from toluene 2,4‐diisocyanate, toluene 2,6‐diisocyanate, and polypropylene glycol with a ratio between the isocyanate and hydroxyl groups equal to 2 were analyzed by ¹H nuclear magnetic resonance (NMR) spectroscopy in acetone‐d₆. Different temperatures and concentrations were used. Toluene 2,4‐dimethylurethane and toluene 2,6‐dimethylurethane were synthesized and used as model compounds to assign prepolymers signals. Measurements of spin–lattice relaxation time T₁ by “inversion recovery” experiments were carried out on toluene 2,4‐diisocyanate, toluene 2,6‐diisocyanate, toluene 2,4‐dimethylurethane, toluene 2,6‐dimethylurethane, and polyurethane prepolymers. Differences in T₁ times were used to interpret prepolymers spectra, by means of the strong observed effect on protons due to the presence of adjacent isocyanate groups. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 347–357, 2003     

An overview of poly(vinyl alcohol) and poly(vinyl pyrrolidone) in pharmaceutical additive manufacturing

Recently, drug personalization has received noticeable attention. Problems arising from standard generalized drug treatments have aroused over the years, particularly among pediatric and geriatric patients. The growing awareness of the limitations of the “one-size-fits-all” approach has progressively led to a rethinking of the current medicine's development, laying the basis of personalized medicine. Three-dimensional printing is a promising tool for realizing personalized therapeutic solutions fitting specific patient needs. This technology offers the possibility to manufacture drug delivery devices with tailored doses, sizes, and release characteristics. Among additive manufacturing techniques, fused deposition modeling (FDM) is the most studied for oral drug delivery device production due to its high precision and cheapness. By playing with factors such as drug loading method, filament production, and printing parameters, the medication release profile of a drug delivery device produced by 3D printing can be tailored depending on the patient's requirements. This review focuses on the applications of FDM in drug fabrication using poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) as drug-loaded matrices. The authors aim to provide an overview of the current trends in this research field, with special attention to the effect of the printing parameters, tablet shape, and drug distribution and concentration on drug customization and personalized drug release.     

Polypropylene/date stone flour composites: Effects of filler contents and EBAGMA compatibilizer on morphology,thermal, and mechanical properties

This work aims to study the effects of date stone flour (DSF) on morphology, thermal, and mechanical properties of polypropylene (PP) composites in the absence and presence of ethylene‐butyl acrylate‐glycidyl methacrylate (EBAGMA) used as the compatibilizer. DSF was added to the PP matrix at loading rates of 10, 20, 30, and 40 wt %, while the amount of compatibilizer was fixed to the half of the filler content. The study showed through scanning electron microscopy analysis that EBAGMA compatibilizer improved the dispersion and the wettability of DSF in the PP matrix. Thermogravimetric analysis (TGA) indicated a slight decrease in the decomposition temperature at onset (T_onset) for all composite materials compared to PP matrix, whereas the thermal degradation rate was slower. Differential scanning calorimetry (DSC) data revealed that the melting temperature of PP in the composite materials remained almost unchanged. The nucleating effect of DSF was however reduced by the compatibilizer. Furthermore, the incorporation of DSF resulted in the increase of stiffness of the PP composites accompanied by a significant decrease in both the stress and strain at break. The addition of EBAGMA to PP/DSF composites improved significantly the ductility due to the elastomeric effect of EBAGMA. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Experimental design of the kinetic resolution of a key precursor of high‐value bioactive myo‐inositols by an immobilized lipase

BACKGROUND: The response surface methodology was successfully applied to the optimization of the reaction variables for the kinetic resolution of a precursor of high‐value myo‐inositols, ( ± )‐1,2‐O‐isopropylidene‐3,6‐di‐O‐benzyl‐myo‐inositol (( ± )‐1), by Novozym 435. The resolutions were run separately, with two acylating agents, ethyl acetate and vinyl acetate, in a solvent‐free system. The variables analyzed were reaction temperature, substrate concentration, water concentration and enzyme activity. A statistical model was employed for the evaluation of the influence of the variables on conversion and enantiomeric excess (ee). RESULTS: The optimal conditions for this resolution using vinyl acetate as acylating agent were 45 °C, 5 mg mL^?1 of substrate, 71 U of enzyme activity and 0%w/w of water concentration. The high conversion (49.2 %) and ee (>99%) reached in the chemoenzymatic synthesis of acylated product, L‐(?)‐5‐O‐Acetyl‐3,6‐di‐O‐benzyl‐1,2‐O‐isopropylidene‐myo‐inositol, secure the efficient synthesis of the D enantiomorph present in the original racemic mixture (( ± )‐1) as well. CONCLUSIONS: The use of the experimental design strategy was productive, leading to a 14‐fold increase in the productivity of the reaction compared with the non‐optimized conditions. Both derivative L‐(?)‐2 and remaining substrate D‐(+)‐1 were obtained at high ee. © 2012 Society of Chemical Industry     

IrO2–SnO2 mixtures as electrocatalysts for the oxygen reduction reaction in alkaline media

In this work, SnO₂ + IrO₂ mixed oxides are studied as electrocatalysts for the oxygen reduction reaction (ORR) in alkaline media by means of voltammetric techniques under controlled mass transfer conditions thanks to the use of rotating (ring) disk electrodes (RDE/RRDE). The oxides, prepared by sol–gel methodology, are supported on the disk electrodes using a thin layer of anionic exchange polymer as gluing agent. The amount of deposited polymer was optimized to avoid any limitation due to the diffusion of reactant/products across the film thickness. The mixed oxides were prepared at the following mole fractions of IrO₂: $ x_{{{\text{IrO}}_{ 2} }} $  = 0.15, 0.31, 0.55, 0.73, and 1. The role of composition was studied in terms of the reaction pathways and the relevant fraction of H₂O₂ production, together with the potentials of the onset of ORR. The fraction of sites able to give proton/hydroxyl and electron transfers is also determined and discussed. The results point to the best performance of low-Ir containing mixtures and to their low sensitivity to the presence of methanol, a key feature in the case of crossover in alkaline direct alcohol fuel cells.     

Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy

Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE), a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents.     

Na-feldspar (F) and kaolinite (K) system at high temperature: Resulting phase composition,micro-structural features and mullite-glass Gibbs energy of formation,as a function of F/K ratio and kaolinite crystallinity

The system Na-feldspar (F) and kaolinite (K) was investigated at temperatures of interest in ceramic applications (1200–1280 °C) to study the effects of F/K ratios by weight and crystallinity degree of kaolinite on the final product, micro-structural features and mullite-glass Gibbs energy of formation (ΔG^eff). Mullite and glass are the dominant phases; in general, the higher the temperature, the larger the former. An F/K increase promotes the formation of glass and secondary mullite, appearing along with the primary one. ΔG^eff was modelled by α(T) × (F/K)² + β(T) × F/K + γ(T), α, β and γ being linear functions of temperature whose coefficients were determined by fitting the ΔG^eff-theoretical to the ΔG^eff-obtained from the measured phase compositions. ΔG^eff is less affected by temperature than by F/K, whose increase shifts equilibrium towards glass phases. The ΔG^eff-curves for ordered and disordered kaolinite intersect one another at F/K ～0.5, a ratio close to that used in industrial practice.     

Wollastonite/hydroxyapatite scaffolds with improved mechanical,bioactive and biodegradable properties for bone tissue engineering

Wollastonite/hydroxyapatite composite scaffolds are proposed as bone graft. An investigation on scaffold with varying reinforcing wollastonite content fabricated by polymeric sponge replica is reported. The composition, sintering behavior, morphology, porosity and mechanical strength were characterized. All the scaffolds had a highly porous well-interconnected structure. A significant increase in mechanical strength is achieved by adding a 50% wollastonite phase. The most mechanically resistant (50/50) wollastonite/hydroxyapatite scaffolds were soaked in both simulated body fluid (SBF) and Tris–HCl solution in order to assess bioactivity and biodegradability. A carbo-hydroxyapatite layer formed on their surfaces when immersed in SBF. The biodegradability tests reveals that the composite scaffold shows a higher degradation rate compared to pure hydroxyapatite used as comparison. These results demonstrate that the incorporation of a 50% of wollastonite phase in hydroxyapatite matrix is effective in improving the strength and the bioactive and biodegradable properties of the porous scaffolds.