Stereoselective interactions of chiral dipeptides on amylose based chiral stationary phases

Dipeptides are stereo-specifically involved in several biological functions that are challenging to separate enantiomerically. Elution order of enantiomers is an important issue in chiral chromatography. Amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase(CSP) is the best and most-widely-used CSP in chiral separations, but experimental data of enantiomeric separation of dipeptides on this CSP is lacking. Simulation studies were conducted to determine the order of elution and the chiral recognition mechanism of didpetides on this CSP. Results indicated that the docking energy of SR-enantiomers were higher than SS-antipodes. The range of docking energies for SR-enantiomers was -7.44 to -5.92 kcal/mol with CSP, but -7.15 to -5.87 kcal/mol for SS-stereoisomers. Therefore it is predicted that SS-enantiomer will elute first, followed by SR-antipode. Furthermore, hydrogen bondings, van der Waal’s interactions and electrostatic interactions were observed among SR- and SSenantiomers and chiral grooves of CSP. The number of hydrogen bonds was one in each enantiomer binding except S-Ala-R-Tyr, which contained two hydrogen bonds. No hydrogen bond was found in S-Ala-R-Trp, S-Leu-S-Trp, and S-Leu-S-Tyr dipeptides bindings. The chiral recognition mechanisms dictate different strengths of stereoselective bindings of the enantiomers on CSP.     

Modeling mechanical properties of polyhydroxyalkanoate during degradation in animal tissue

Polyhydroxyalkanoates (PHAs) are a family of biodegradable and biocompatible polymers produced by several species microorganisms that possess favorable mechanical properties (e.g. strength and elongation properties). Different types of PHA polymers have been used in medical applications. However, in order to better understand the use of this polymer in the different applications, a thorough understanding of the kinetics of in vivo degradation is one of the major requirements. In this study, poly(3‐hydroxybutyrate) (PHB) was subcutaneously implanted in mice and incubated for 2, 4, 8, or 16 weeks. After removal from the animal, the strength, elongation, mass loss, and enthalpy of the PHB were tested for each time point. From these data, a mathematical model was generated by Rayleigh's method of dimensional analysis, where polymer strength over tissue contact time could be predicted. To prove the model, previous data obtained by our group were used: poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) [P(HB‐co‐HHx)] incubation in the presence of human embryonic kidney cells (HEK). It was found that the developed model was aligned with experimental results, could predict the strength of the polymer when in contact with cells, and the predicted strength follows the trend of the experimental data. Also, the dimensionless constant (K) value associated with the model is different for both experiments, where this constant, produced via experimental data, is used for construction of a homogeneous equation. Copyright © 2017 John Wiley & Sons, Ltd.     

Preparation and Evaluation of Long Chain Alkyl Methacrylate Monoliths for Capillary Chromatography

This work describes the fabrication of long chain alkyl methacrylate monolithic materials for use as stationary phases in capillary liquid chromatography. After capillary inner wall surface activation with 3-(trimethoxysilyl)propyl methacrylate, monoliths were formed by copolymerization of either lauryl or stearyl methacrylate (LMA or SMA) with ethylene dimethacrylate (EDMA) as crosslinker, in the presence of azobisisobutyronitrile (AIBN) as initiator and a mixture of porogenic solvents including water, 1-propanol and 1,4-butanediol. The composition of the polymerization mixture was changed in terms of monomer, crosslinker and porogen ratio composition, in order to compare the influence of these parameters. The monoliths were prepared in 320 ??m i.d. and 200 mm length capillaries. The column morphology was characterized by optical microscopy and scanning electron microscopy (SEM). Total porosity and permeability of each column were calculated using uracil as unretained material by measuring the pressure drop across the columns as a function of linear velocity. The microglobule average size for each column was also determined using Hagen?CPoiseuille equation and compared with the SEM images. As expected, a decrease of the porogen to monomer ratio corresponded to smaller microglobules and a lower total porosity. The columns were then chromatographically evaluated; good results were obtained when these capillaries were used to separate mixtures of phenols, aromatics and drug compounds.     

Kinetics and safety analysis of sulfide mineral self-heating

Thermal methods of analysis such as DSC and TGA provide a powerful methodology for the study of solid reactions. This paper proposes an improved thermal analysis methodology for thermal stability and safety investigation of complex solid-state reactions. The proposed methodology is based on differential iso-conversional approach and involves peak separation and individual peak analysis for kinetic analysis and safety prediction. The proposed thermal analysis method was coupled with Mineral Libration Analysis (MLA) to investigate self-heating of sulfide mineral ores. The influence of sample’s mineralogy on thermal degradation was examined and discussed. The information gained from the advanced kinetic analysis of DSC/TGA measurements were up-scaled for TMR and SADT determination. The described thermal analysis method provides not only an understanding of sulfide mineral self-heating, but also aids the design of effective mitigation measures for their adverse environmental and safety effects.     

In Silico Approach Using Free Software to Optimize the Antiproliferative Activity and Predict the Potential Mechanism of Action of Pyrrolizine-Based Schiff Bases

In the current study, a simple in silico approach using free software was used with the experimental studies to optimize the antiproliferative activity and predict the potential mechanism of action of pyrrolizine-based Schiff bases. A compound library of 288 Schiff bases was designed based on compound 10, and a pharmacophore search was performed. Structural analysis of the top scoring hits and a docking study were used to select the best derivatives for the synthesis. Chemical synthesis and structural elucidation of compounds 16a–h were discussed. The antiproliferative activity of 16a–h was evaluated against three cancer (MCF7, A2780 and HT29, IC₅₀ = 0.01–40.50 μM) and one normal MRC5 (IC₅₀ = 1.27–24.06 μM) cell lines using the MTT assay. The results revealed the highest antiproliferative activity against MCF7 cells for 16g (IC₅₀ = 0.01 μM) with an exceptionally high selectivity index of (SI = 578). Cell cycle analysis of MCF7 cells treated with compound 16g revealed a cell cycle arrest at the G₂/M phase. In addition, compound 16g induced a dose-dependent increase in apoptotic events in MCF7 cells compared to the control. In silico target prediction of compound 16g showed six potential targets that could mediate these activities. Molecular docking analysis of compound 16g revealed high binding affinities toward COX-2, MAP P38α, EGFR, and CDK2. The results of the MD simulation revealed low RMSD values and high negative binding free energies for the two complexes formed between compound 16g with EGFR, and CDK2, while COX-2 was in the third order. These results highlighted a great potentiality for 16g to inhibit both CDK2 and EGFR. Taken together, the results mentioned above highlighted compound 16g as a potential anticancer agent.     

PMR Spectrometric Analysis of Tolmetin Sodium in Capsules Forms

An analytical method is described for the assay of tolmetin, 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetic acid, as sodium salt, (Tolectin[rgrave] - 200 mg) using PMR. The protocol reported in this study is simple, precise and yields accurate results of 99.78±0.84 and 100.67±2.08 for the authentic material and capsules respectively. In addition, the PMR spectrum obtained provides a means for qualitative identification of the drug and checking its purity. The principle of the method involves comparison of the integral of the well-defined singlet (positioned at 2.41 Δ) to that of the sharp singlet due -CH₃ (positioned at 1.91 Δ) of sodium acetate as an internal standard in presence of maleic acid using DMSO-d₆ solvent. The rationale for the use of maleic acid in the assay procedure has been discussed.     

Estimates of axion signal from positronium decay

Numerical values for axion decay channel branching ratio in positronium decays are presented. From the ³S₁ state the maximum is of the order of 10^?6. If the axion mass were to be in the vicinity of the positronium mass, the best way of observing the signal would be the decay from the 2¹P₁ state. The feasibility of attaining this by optical pumping is indicated.     

On the validity of the non-perturbative solutions for multiphoton processes at high intensities

It is shown that a unifying sufficient condition for the validity of two classes of non-perturbative solutions to multiphoton transitions to be found in the literature, is the requirement of spectral degeneracy of the target Hamiltonian.