Conformational stability, r 0 structural parameters, barriers to internal rotation, ab initio calculations, and vibrational assignment for 2,2-difluoroethanol

The infrared spectra (4,000–30 cm^?1) of the gas and solid and the Raman spectrum of liquid 2,2-difluoroethanol as well as variable temperature infrared spectra of krypton/xenon solutions have been recorded. From all these data, two (Gg and Tg) out of the five possible stable conformers have been confidently identified. The order of the stabilities has been predicted to be Gg > Tg > Gt > Gg′ > Tt by utilizing ab initio MP2 (full) and DFT (B3LYP method) calculations, where the first indicator (capital letter) is in reference to rotation around the C–C bond (G = gauche or T = trans) and the second one (small letter) refers to the orientation of the hydroxyl group. The percentage of the minor conformer Tg, at ambient temperature, is estimated to be (16 ± 3%). The optimized geometries, fundamental frequencies, infrared intensities, Raman activities, and depolarization values as well as centrifugal distortion constants have been obtained from ab initio and density functional theory calculations by utilizing a variety of basis sets as well as those with diffuse functions. By utilizing the previously reported microwave rotational constants for two isotopomers of the Gg conformer combined with ab initio MP2(full)/6-311+G(d,p) predicted structural values, adjusted r ₀ parameters have been obtained. The determined heavy atom distances (Å) for the Gg conformer are: C₁–C₂ = 1.510(3), C₂–F₄ = 1.371(3), C₂–F₅ = 1.362(3), C₁–O₃ = 1.412(3) Å and angles ∠O₃C₁C₂ = 111.0(5), ∠F₄C₂C₁ = 108.8(5), ∠F₅C₂C₁ = 109.8(5), τF₄C₂C₁O₃ = 63.5(5), τF₅C₂C₁O₃ = 179.1(5)°. Barriers of internal rotation have been obtained and vibrational assignments for the Gg and Tg conformers are given. The five predicted centrifugal distortion constants compared to the experimental values are in reasonable agreement except for ?_K, which appears to be in error. The results are discussed and the structural parameters compared to the corresponding ones for 2-fluoroethanol and 2,2,2-trifluoroethanol where those for the latter molecule have been redetermined. The currently determined heavy atom parameters are quite different from the earlier assumed values, which led to poor values of the six adjusted parameters.     

METHOD OF CENTERS ALGORITHM FOR MULTI-OBJECTIVE PROGRAMMING PROBLEMS

In this paper, we consider a method of centers for solving multi-objective programming problems, where the objective functions involved are concave functions and the set of feasible points is convex. The algorithm is defined so that the sub-problems that must be solved during its execution may be solved by finite-step procedures. Conditions are given under which the algorithm generates sequences of feasible points and constraint multiplier vectors that have accumulation points satisfying the KKT conditions. Finally, we establish convergence of the proposed method of centers algorithm for solving multiobjective programming problems.     

A novel design approach for the epitaxial layer for 4H-SiC and 6H-SiC power bipolar devices

The paper evaluates the optimal design of the low-doped base region inside power diodes and other bipolar devices. It is demonstrated theoretically that a low-doped base region of P⁺N⁻N⁺ diodes can provide a high breakdown voltage and an optimal on-resistance . A simple, accurate and CPU timesaving approach is presented to extract an optimal value for the base region width, W_B, and its doping concentration, N_D. The paper details an analytical relation between W_B and N_D, and gives a method for quantifying the trade-off between their values for a given breakdown voltage and for obtaining the minimal on-resistance. Analytical results are confronted with experimental results for 4H-SiC- and 6H-SiC-based diodes.     

A search-and-track algorithm for controlling the number of guided modes of planar optical waveguides with arbitrary refractive index profiles

A search-and-track algorithm is proposed for controlling the number of guided modes of planar optical waveguides with arbitrary refractive index profiles. The algorithm starts with an initial guess point in the parameter space that supports a specific number of guided modes. Then, it searches for, and tracks, the boundaries of this space or another space supporting different number of modes. It does so by monitoring the sign of a unified cutoff dispersion function. The algorithm is applied to both symmetric and asymmetric silicon-based parabolic-index waveguides. It shows that unlike asymmetric waveguides, the single-mode condition of symmetric waveguides is controlled by TM-, as opposed to TE-, polarization. This abnormal polarization control is strongest for high index contrast waveguides of sub-micrometer core sizes. The results are verified by full-vectorial beam propagation method.     

Synthesis and preliminary investigations of the siRNA delivery potential of novel, single-chain rigid cationic carotenoid lipids

The success of nucleic acid delivery requires the development of safe and efficient delivery vectors that overcome cellular barriers for effective transport. Herein we describe the synthesis of a series of novel, single-chain rigid cationic carotenoid lipids and a study of their preliminary in vitro siRNA delivery effectiveness and cellular toxicity. The efficiency of siRNA delivery by the single-chain lipid series was compared with that of known cationic lipid vectors, 3β-[N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol) and 1,2-dimyristoyl-sn-glyceryl-3-phosphoethanolamine (EPC) as positive controls. All cationic lipids (controls and single-chain lipids) were co-formulated into liposomes with the neutral co-lipid, 1,2-dioleolyl-sn-glycerol-3-phosphoethanolamine (DOPE). Cationic lipid-siRNA complexes of varying (+/-) molar charge ratios were formulated for delivery into HR5-CL11 cells. Of the five single-chain carotenoid lipids investigated, lipids 1, 2, 3 and 5 displayed significant knockdown efficiency with HR5-CL11 cells. In addition, lipid 1 exhibited the lowest levels of cytotoxicity with cell viability greater than 80% at all (+/-) molar charge ratios studied. This novel, single-chain rigid carotenoid-based cationic lipid represents a new class of transfection vector with excellent cell tolerance, accompanied with encouraging siRNA delivery efficiency.     

New HPLC method to detect individual opioids (heroin and tramadol) and their metabolites in the blood of rats on combination treatment

Drug abuse is both an age-old and a constantly evolving problem in society. Trends in illicit drug use are highly fluid, with new formulations increasing in popularity. For this reason, methods for illicit drug detection and analysis need to be continually updated so they remain useful and relevant. A recent trend in street heroin production has seen it diluted with large amounts of tramadol in addition to the classical diluents such as acetaminophen and caffeine. This study describes a sensitive, simple and accurate high-performance liquid chromatographic method with ultraviolet detection for the simultaneous detection of heroin, 6-acetylmorphine, morphine, tramadol and O-desmethyltramadol in the blood of rats using a liquid-liquid back-extraction method. The separation was performed on LichroCART RP-18e with particle size of 5 μm (250 × 4.6 mm) with mobile phase acetonitrile-50 mM KH(2)PO(4) buffer, pH 7.1, using a gradient mode with a 1.0 mL/min flow rate. The calibration curves were linear in the concentration ranges 0.25-100 and 0.1-100 μg/mL for morphine and other analytes, respectively. Recovery values for the substances ranged between 59 and 83%. This technique was successfully used in pharmacokinetic studies measuring 6-acetylmorphine, morphine, tramadol and O-desmethyltramadol in the blood of rats intraperitoneally treated with a blend of 10 mg/kg heroin and 70 mg/kg tramadol. This technique shows promise for analysis of confiscated street heroin.     

Gradient HPLC-DAD stability indicating determination of miconazole nitrate and lidocaine hydrochloride in their combined oral gel dosage form

The pharmaceutical combination of miconazole nitrate (MZ) and lidocaine hydrochloride (LD) is used in the curative and prophylactic therapy of the oral and gastro-intestinal infections caused by Candida albicans. To the best of our knowledge, no attempts have yet been made to assay this combination by any analytical method. A simple and selective high-performance liquid chromatography-diode array detection (HPLC-DAD) stability-indicating method was developed for the simultaneous determination of MZ and LD in their combined formulation. Effective chromatographic separation was achieved using a Zorbax SB-C8 column with gradient elution of the mobile phase composed of 0.05 M phosphoric acid and acetonitrile. The gradient elution started with 25% (by volume) acetonitrile, ramped up linearly to 65% in 6 min, then kept constant until the end of the run. The mobile phase was pumped at a flow rate of 1 mL/min. The multiple wavelength detector was set at 215 nm and analytes were quantified by measuring their peak areas. The retention times for LD and MZ were approximately 4.1 and 8.4 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection and quantification limits. Calibration curves were linear in the ranges of 5-100 μg/ml for both drugs with correlation coefficients > 0.999. Both drugs were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The proposed method proved to be stability-indicating by the resolution of the two analytes from the related substance and potential impurity (2,6-dimethylaniline) and from the forced-degradation products. The validated HPLC method was applied to the analysis of MZ and LD in the combined oral gel preparation, in which the two analytes were successfully quantified and resolved from the pharmaceutical additives. The proposed method made use of DAD as a tool for peak identity and purity confirmation.     

Evaluation of Matrix-Fracture Transfer Functions for Counter-Current Capillary Imbibition

Different functions describing matrix-fracture transfer were tested for counter-current capillary imbibition interaction. The recovery curves obtained from capillary imbibition experiments were used to fit the transfer functions. The exponential coefficients yielding the best fit to the experimental data were obtained and correlated to the effective parameters such as viscosity, IFT, matrix length and diameter, matrix permeability and porosity, and wettability using multivariable regression analysis. In order to obtain the recovery curves, experiments were conducted on Berea sandstone and Indiana limestone samples. Cylindrical samples with different shape factors were obtained by cutting the plugs 1, 2.5, and 5 cm in diameter and 2.5, 5, and 10 cm in length. All sides were coated with epoxy except one end. More than fifty static imbibition experiments were carried out on vertically and horizontally situated samples where the imbibition took place upward and lateral directions, respectively. Brine–air, brine–kerosene, brine–mineral oil, and surfactant solution–mineral oil pairs were used as fluids. For many matrix shape factors (especially longer and small diameter ones), dividing the recovery curve into three parts were needed as the early, intermediate, and late times, which are typically distinguished by the time required for the imbibition front to reach the closed boundary at the end of the core. Correlations among the exponential coefficients and rock/fluid properties were developed. It was observed that different rock/fluid properties and transfer mechanisms (capillary imbibition and gravity drainage) govern the process for each part. Hence, the analyses done in this study were useful not only for developing explicit transfer functions but also identifying the physics of the counter-current imbibition recovery.     

Optimized Green Extraction of Polyphenols from Cassia javanica L. Petals for Their Application in Sunflower Oil: Anticancer and Antioxidant Properties

The total phenolic content (TPC) from Cassia javanica L. petals were extracted using ethanolic solvent extraction at concentrations ranging from 0 to 90% and an SCF-CO₂ co-solvent at various pressures. Ultrasound-assisted extraction parameters were optimized using response surface methodology (RSM). Antioxidant and anticancer properties of total phenols were assessed. An SCF-CO₂ co-solvent extract was nano-encapsulated and applied to sunflower oil without the addition of an antioxidant. The results indicated that the best treatment for retaining TPC and total flavonoids content (TFC) was SCF-CO₂ co-solvent followed by the ultrasound and ethanolic extraction procedures. Additionally, the best antioxidant activity by β-carotene/linoleic acid and DPPH free radical-scavenging test systems was observed by SCF-CO₂ co-solvent then ultrasound and ethanolic extraction methods. SCF-CO₂ co-solvent recorded the highest inhibition % for PC3 (76.20%) and MCF7 (98.70%) and the lowest IC₅₀ value for PC3 (145 µ/mL) and MCF7 (96 µ/mL). It was discovered that fortifying sunflower oil with SCF-CO₂ co-solvent nanoparticles had a beneficial effect on free fatty acids and peroxide levels. The SCF-CO₂ method was finally found to be superior and could be used in large-scale processing.     

Synthesis of Potential Antiviral Agents for SARS-CoV-2 Using Molecular Hybridization Approach

We synthesized a set of small molecules using a molecular hybridization approach with good yields. The antiviral properties of the synthesized conjugates against the SAR-CoV-2 virus were investigated and their cytotoxicity was also determined. Among all the synthesized conjugates, compound 9f showed potential against SARS-CoV-2 and low cytotoxicity. The conjugates’ selectivity indexes (SIs) were determined to correlate the antiviral properties and cytotoxicity. The observed biological data were further validated using computational studies.