Homopolymer and copolymers of 4-nitro-3-methylphenyl methacrylate with glycidyl methacrylate: Synthesis, characterization, monomer reactivity ratios and thermal properties

The novel methacrylic monomer, 4-nitro-3-methylphenyl methacrylate (NMPM) was synthesized by reacting 4-nitro-3-methylphenol dissolved in ethyl methyl ketone (EMK) with methacryloyl chloride in the presence of triethylamine as a catalyst. The homopolymer and copolymers of NMPM with glycidyl methacrylate having different compositions were synthesized by free radical polymerization in EMK solution at 70 ± 1 °C using benzoyl peroxide as free radical initiator. The homopolymer and the copolymers were characterized by FT-IR, ¹H NMR and ¹³C NMR spectroscopic techniques. The solubility tests were tested in various polar and non-polar solvents. The molecular weight and polydispersity indices of the copolymers were determined using gel permeation chromatography. The glass transition temperature of the copolymers increases with increase in NMPM content. The thermogravimetric analysis of the polymers performed in air showed that the thermal stability of the copolymer increases with NMPM content. The copolymer composition was determined using ¹H NMR spectra. The monomer reactivity ratios were determined by the application of conventional linearization methods such Fineman-Ross (r₁ = 1.862, r₂ = 0.881), Kelen-Tudos (r₁ = 1.712, r₂ = 0.893) and extended Kelen-Tudos methods (r₁ = 1.889, r₂ = 0.884).     

Preparation of polyaniline‐sulfate salt ­by emulsion and aqueous ­polymerization pathway without using ­protonic acid

Aniline was polymerized directly into polyaniline‐sulfate salt without using protonic acid in this work. Polyaniline‐sulfate salt was prepared by emulsion and aqueous polymerization pathways. The dopant i.e. sulfate ion in polyaniline‐sulfate salt was generated from ammonium persulfate which was used for oxidizing aniline. Ammonium persulfate acts both as oxidizing agent as well as protonating agent in the polymerization process of aniline to polyaniline salt. The efficiency of oxidizing and protonating power of ammonium persulfate is increased by the use of surfactant. The activity of ammonium persulfate is further increased by the use of sulfuric acid as protonic acid. It may be necessary to consider the effect of sulfate ion which is generated during the oxidation process of aniline in the chemical polymerization of aniline to polyaniline salt by ammonium persulfate either aqueous or emulsion polymerization pathway in the presence of protonic acid/functionalized protonic acid. Copyright © 2001 John Wiley & Sons, Ltd.     

Rapid determination of desorption efficiency, and analysis of solvent mixtures for occupational exposure studies

Summary An analytical procedure has been developed for simultaneous determination of solvent mixture vapors to enable evaluation of occupational exposure. To determine the desorption efficiency the volatile components of the solvent mixtures were generated from a glass tube filled with glass wool. This device is easy to prepare and use. These vapors were then collected in activated charcoal tubes and analyzed by capillary gas chromatography. The method was tested with a mixture of 22 solvents, including aliphatic and aromatic hydrocarbons, alcohols, ethers, esters, and ketones, all at low concentrations. All the components were detected. When a 99∶1 mixture of carbon disulfide-dimethylformamide was used for desorption the efficiency was>75% for most of the solvents.     

Enhancement of Oral Bioavailability of Rofecoxib Using β-Cyclodextrin

The purpose of the present work was to investigate the effect ofcomplexation of rofecoxib with -cyclodextrin on its dissolutioncharacteristics and bioavailability. Inclusion complexes of rofecoxibwith -cyclodextrin were made by freeze-drying technique. Phasesolubility studies were conducted as suggested by Higuchi and Connors.The samples were characterized by performing dissolution studies, X-rayDiffraction studies and Differential Scanning Calorimetry. The complexeswere compressed into tablets and compared in-vitro with various marketedformulations. A single dose study on healthy human volunteers was performedin comparison with a marketed formulation of rofecoxib (without-cyclodextrin) to investigate the relative bioavailability.Phase solubility studies confirmed the formation of a 1 : 1complex in solution of rofecoxib with -cyclodextrin. Tablets ofsolid inclusion complexes of rofecoxib with -cyclodextrin preparedby freeze drying technique showed enhanced dissolution rate in distilledwater in comparison with all the marketed formulations analyzed. This isattributed to the increased solubility and wettability along with decreasedcrystallinity caused by complex formation, which is confirmed, by XRD and DSCstudies. The bioequivalence studies performed showed statistically significantenhancement in bioavailability as compared to the marketed formulation.Apparently, tablets containing complexes of rofecoxib with -cyclodextrinshows faster onset of action due to improved solubility, enhanced dissolutionand faster absorption of the molecule. The results of this investigation withrofecoxib in -cyclodextrin lend ample credence to its better oralbioavailability on complexation.     

Calorimetric study of cesium hexafluoroarsenate CsAsF<Subscript>6</Subscript> at elevated temperatures

Summary Cobalt(II), nickel(II) and copper(II) complexes of some aroylhydrazone Schiff’s bases derived from isoniazide (hydrazide of isonicotinic acid) with p-hydroxybenzaldehyde; 2,4-dihydroxybenzaldehyde or 2-hydroxy-1-naphthaldehyde are prepared and characterized. The study reveals that the ligands coordinate in the keto form. That transformed to the enol through the loss of HCl upon heating the solid complexes. The copper(II) complexes are thermochromic in the solid-state while the cobalt(II) complex, 3 of 2,4-dihydroxybenzaldehyde moiety is solvatochromic in hot DMF. The chromisms obtained were discussed in terms of change in the ligand field strength and/or coordination geometry.     

Conformational studies of soluble and immobilized frog epidermis tyrosinase by fluorescence

Fluorescence spectra and soluble quenching of intrinsic protein fluorescence were used as indexes of conformational changes suffered by frog epidermis tyrosinase. The activation process and the immobilization of the enzyme involving either free amino groups or its carbohydrate moiety were studied. The conformational changes resulting from denaturation of each one of the protein derivatives, as well as the effect of active center copper extraction, were followed by fluorescence studies. The results showed that: (a) both activation and immobilization were accompanied by conformational changes of the protein leading to more unfolded states; (b) neither enzyme nor immobilized enzyme were fully unfolded upon denaturation although enzymic activity was lost; (c) the enzyme immobilized through its carbohydrate moiety was more unfolded upon denaturation than the enzyme immobilized through amino groups, thus pointing to a higher conformational stabilization in the last situation; and (d), that tryptophyl residues moved to a localization near the active site upon activation.     

High speed liquid chromatography with small bore columns

Using a specially designed column system, we have systematically investigated the effect of mobile phase velocity on column efficiency. The performance of small bore columns operated at different linear velocities of mobile phase was examined for three different types of injection system. Using the value of H^∞/u or n^∞/t${}_{\text{r}}^{\text{º}}$ as a criterion of a high speed separation, we calculated values of n/t${}_{\text{r}}^{\text{º}}$ for different solutes according to the equation \documentclass{article}\pagestyle{empty}\begin{document}$ {{\rm n}\mathord{\left/ {\vphantom {{\rm n} {{\rm t}_{\rm r}^ \circ }}}\right. \kern-\nulldelimiterspace} {{\rm t}_{\rm r}^ \circ }} = {{{\rm n}^\infty } \mathord{\left/ {\vphantom {{{\rm n}^\infty } {{\rm t}_{\rm r}^ \circ }}} \right. \kern-\nulldelimiterspace} {{\rm t}_{\rm r}^ \circ }}\left({\frac{{1 + {\rm k'}}}{{{\rm k' + }\beta }}} \right)^2 $\end{document}; the results obtained are in agreement with the experimentally determined values. These systematic investigations culminated in the separation of seven compounds in less than 10 s; the respective chromatogram is shown.     

Unveiling the Hidden Therapeutic Potential of Carnosine,a Molecule with a Multimodal Mechanism of Action: A Position Paper

Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous dipeptide and an over-the-counter food supplement with a well-demonstrated multimodal mechanism of action that includes the detoxification of reactive oxygen and nitrogen species, the down-regulation of the production of pro-inflammatory mediators, the inhibition of aberrant protein formation, and the modulation of cells in the peripheral (macrophages) and brain (microglia) immune systems. Since its discovery more than 100 years ago, a plethora of in vivo preclinical studies have been carried out; however, there is still substantial heterogeneity regarding the route of administration, the dosage, the duration of the treatment, and the animal model selected, underlining the urgent need for “coordinated/aligned” preclinical studies laying the foundations for well-defined future clinical trials. The main aim of the present position paper is to critically and concisely consider these key points and open a discussion on the possible “alignment” for future studies, with the goal of validating the full therapeutic potential of this intriguing molecule.     

Simultaneous Estimation of Escitalopram and Clonazepam in Tablet Dosage Forms Using HPLC-DAD Method and Optimization of Chromatographic Conditions by Box-Behnken Design

The study aimed to develop a new reverse-phase high-performance liquid chromatography (RP-HPLC) method with diode array detection (DAD) detection for simultaneous estimation of escitalopram (EST) and clonazepam (CZP) in tablet dosage forms with a quality by design (QbD) approach. The chromatographic conditions were optimized by Box-Behnken design (BBD) and developed method was validated for the linearity, system suitability, accuracy, precision, robustness, sensitivity, and solution stability according to International Council for Harmonization (ICH) guidelines. EST and CZP standard drugs peaks were separated at retention times of 2.668 and 5.046 min by C-18 column with dimension of 4.6 × 100 mm length and particle size packing 2.5 µm. The mobile phase was methanol: 0.1% orthophosphoric acid (OPA) (25:75, v/v), with a flow rate of 0.7 mL/min at temperature of 26 °C. The sample volume injected was 20 µL and peaks were detected at 239 nm. Using the standard calibration curve, the % assay of marketed tablet was founded 98.89 and 98.76 for EST and CZP, respectively. The proposed RP-HPLC method was able to detect EST and CZP in the presence of their degradation products, indicating the stability-indicating property of the developed RP-HPLC method. The validation parameter’s results in terms of linearity, system suitability, accuracy, precision, robustness, sensitivity, and solution stability were in an acceptable range as per the ICH guidelines. The newly developed RP-HPLC method with QbD application is simple, accurate, time-saving, and economic.     

The Effectiveness of Rhodiola rosea L. Preparations in Alleviating Various Aspects of Life-Stress Symptoms and Stress-Induced Conditions—Encouraging Clinical Evidence

Rhodiola rosea L. has a long history of use in traditional medicine to stimulate the nervous system, treat stress-induced fatigue and depression, enhance physical performance and work productivity and treat gastrointestinal ailments and impotence. Apart from its well-established traditional use, a significant number of publications on the clinical efficacy of various R. rosea preparations can be found in the literature. The majority of these studies are related to the efficacy of R. rosea in terms of cognitive functions and mental performance, including various symptoms of life-stress, fatigue and burnout. The beneficial effects of this medicinal plant on enhancing physical performance have also been evaluated in professional athletes and non-trained individuals. Moreover, even though most evidence originates from pre-clinical trials, several clinical studies have additionally demonstrated the remediating effects of R. rosea on cardiovascular and reproductive health by addressing non-specific stress damage and reversing or healing the disrupted physiologies and disfunctions. Overall, in accordance with its aim, the results presented in this review provide an encouraging basis for the clinical efficacy of R. rosea preparations in managing various aspects of stress-induced conditions.