Application of thermal analysis to the study of antituberculosis drugs–excipient compatibility

First-line drugs (rifampicin, RIF; isoniazid, INH; ethambutol, ETA; and pyrazinamide, PZA) recommended in conventional treatment of tuberculosis were analyzed in 1:1 w/w binary mixtures with microcrystalline cellulose MC 101 (CEL) and lactose supertab^® (LAC) by differential scanning calorimetry (DSC), thermogravimetry (TG), differential thermal analysis (DTA), and Fourier transformed infrared analysis (FTIR) as part of development of fixed dose combination (FDC) tablets. Evidence of interaction between drug and pharmaceutical excipients was supposed when peaks disappearance or shifting were observed on DTA and DSC curves, as well as decreasing of decomposition temperature onset and TG profiles, comparing to pure species data submitted to the same conditions. LAC was showed to interact with RIF (absence of drug fusion and recrystallization events on DSC/DTA curves); INH (thermal events of the mixtures different from those observed for drug and excipient pure in DSC/DTA curves); PZA (decrease on drug fusion peak in DSC/DTA curves), and ETA (shift on drug onset fusion and absence of pure LAC events on DSC/DTA curves). In all cases, an important decrease on the temperature of drug decomposition was verified for the mixtures (TG analysis). However, FTIR analysis showed good correlation between theoretical and experimental drug-LAC spectra except for INH–LAC mixture, evidencing high incompatibility between these two species and suggesting that those interactions with PZA and RIF were thermally induced. No evidence of incompatibilities in CEL mixtures was observed to any of the four-studied drugs.     

Vitamin E – a new choice for polyolefin stabilization

Vitamin E based systems provide an alternative way to stabilize polyolefins, instead of the current state-of-the-art stabilizers, for certain niche applications. Its very positive public perception together with its excellent ability for melt flow control at a very low concentration can be utilized to a great extent, particularly for special applications like food and medical packaging. Thus, it's use can lead to an overall reduction in the total amount of additive required compared to a traditional stabilization system in certain applications. Other potential benefits, resulting from the positive attributes of Vitamin E, include low migration, high extraction resistance, very good organoleptics, gel suppression, and longer shelf-life of products. This study examines the performance of Vitamin E based systems in LDPE, LLDPE, HDPE and PP.     

Simultaneous HPLC–DAD Determination of Retinol and Eight Vitamin E Isomers in Human Serum

An efficient, high-performance liquid-chromatographic method with diode-array detection (HPLC–DAD) has been established for simultaneous determination of retinol, α, (β + γ), and δ-tocopherols, and α, β, γ, and δ-tocotrienols in human serum. After deproteinization, the target vitamins in serum were extracted with n-hexane and the extract was evaporated under weak nitrogen flow. The residue was redissolved in methanol and the resulting solution was used for HPLC analysis. Retinol acetate and α-tocopherol acetate were used as internal standards. The internal standard calibration curves were linear over the range of 0.010–50.0 µg mL⁻¹, with correlation coefficients >0.999. Mean recoveries of the method were 86.3–110 %, with intra-day and inter-day relative standard deviations less than 12.2 and 14.9 %, respectively. The detection limits of the method ranged from 0.001 to 0. 002 µg mL⁻¹, and the quantification limits ranged from 0.002 to 0.008 µg mL⁻¹. The method was successfully applied to analysis of the target vitamins in 50 human serum samples; all the analytes were detected at concentrations ranging from <0.002–23.0 µg mL⁻¹.

     

Novel Industrial Application of Miniemulsion Polymerization – Use of Alkali Soluble Resin as Surfactant in Miniemulsion Polymerization

Nowadays, the great versatility of the miniemulsion polymerization technique to synthesize novel and high value added materials attracts great interest from both the academic and the industrial community. Recently, a novel process based on the use of alkali soluble resin (ASR) as sole surfactant in miniemulsion polymerization for high solids content latexes has been disclosed. This new technology opens a vast field for the production of high performance latexes for industrial applications, as well as an interesting topic for future academic research. This work presents the key factors influencing the use of ASR in aqueous polymer dispersions, highlighting the differences in terms of types and concentrations of ASR used in conventional and miniemulsion polymerization. The effects of type of initiator, ASR concentration and type, as well as solids content on the miniemulsion polymerization of styrene and acrylic monomers are presented.     

Stereospecifical Preparation of (E)-a-Stannyl-1-alkenylphosphonates and their Application in Stille Reaction

1-Alkenylphosphonates are very useful compounds for organic transformations1 and for the synthesis of biological active compounds 2. On the other hand, alkenylstannes are of particular synthetic interest and have attracted a great deal of attention in recent years3. For this reason, we anticipate the a-stannyl-1-alkenylphosphonates, a new class of 1, 1- difunctional reagents which combined a-stannyl and phosphonate groups in one molecule, will play an important role in organic synthesis. Th…     

Application of multi-capillary column – ion mobility spectrometry (MCC-IMS) in rubber chemistry and technology

In this paper the possibility for authentication and differentiation of various styrene butadiene rubbers (SBRs) was investigated. Seven types of SBR were analyzed by multi-capillary column (MCC) ion mobility spectrometer (IMS) and their spectra compared. The analysis of volatile organic compounds (VOCs) releasing from the rubbers revealed the presence of characteristics signals, which can be assigned only to a specific material. Such “markers”, when defined for other polymer materials, can be used for their authentication. In the second part of the paper, the blend of epoxidized natural rubber and poly-3-hydroxybutyrate-co-4-hydroxybutyrate (ENR/P(3,4)HB) was subjected to different types of aging. MCC-IMS spectra of not aged, thermal, climatic and UV aged samples were collected and differences between the signals discussed. The study showed possibility of authentication of polymeric materials and processes. The paper is a some kind of introduction to the use of analytical properties and advantages of MCC-IMS technique in chemistry, technology and exploitation of polymer materials.     

Application Relevant Studies of Fungal β-galactosidases with Potential Application in the Alleviation of Lactose Intolerance

Functional screening studies revealed that Aspergillus carbonarius ATCC6276 produced extracellular β-galactosidase activity potentially suited for use as a lactase digestive supplement in the treatment of lactose intolerance. The crude preparation contained two β-galactosidase activities, β-gal 1 and β-gal 2, which were separated by ion-exchange chromatography. Both enzymes were purified to homogeneity by a combination of gel filtration, ion-exchange, chromatofocusing and hydrophobic interaction chromatographies. β-gal 1 and β-gal 2 displayed differences in molecular mass (110 kDa versus 120 kDa as judged by SDS PAGE) and in a range of additional physicochemical properties. Km values of 83 and 309 mM, respectively, were recorded using lactose as substrate while temperature optima of 55°C versus 65°C were obtained. Unlike current commercialized supplemental lactases, both of the purified enzymes displayed significant stability when exposed to simulated gastric conditions, with β-gal 1in particular retaining 70% residual activity after exposure to pH 2.0 in the presence of pepsin for 2 h. Overall the results indicate that the β-galactosidases of Aspergillus carbonarius ATCC6276, either individually or in combination, may be suitable for use as a digestive supplement for the alleviation of lactose intolerance.     

Stereoselective Synthesis of （E）-α-Aryltellurenylvinyl-stannanes and Their Application in the Synthesis of Stereodefined Trisubstituted Alkenes

(E)-α-Aryltellurenylvinylstannanes have been synthesized stereoselectively via the hydrozirconation of alkynylstannanes, followed by the reactions with aryltellurenyl iodides. (E)-α-Aryltellurenylvinylstannanes can undergo sequential cross coupling reactions with both electrophiles and nucleophiles in the presence of transition metal complexes to form two carbon-carbon bonds in the same olefinic carbon leading to trisubstituted alkenes stereoselectively.     

Stereospecifical Preparation of （E）-α-Stannyl-1-alkenylphosphonates and their Application in Stille Reaction

The palladium catalyzed hydrostannation of 1-alkenylphosphonates gives the (E)-α-stannyl 1-alkenylphosphonates 2 stereospecifically. Compounds 2 can occur Stille coupling reaction to afford α, β-disubstituted vinylphosphonates with the retention of the configuration.     

Insilico validation and comparison of antifungal competence and druglikeness of some natural xanthones – A step towards antimycotic therapeutics

In the current work, the xanthones (from the plant source) that possess strong experimental evidences for their antifungal properties are chosen from the literatures and docking studies were employed with a fungal protein for computational validation to simplify the process of electing the top hits among a large set of naturally occurring substituted xanthones. The results indicate that computationally 86% of xanthones under study exhibits good binding affinity towards (B.E ≥ ?7 kcal/mol) the target protein (GlcN-6-P). The current docking analysis established the Garcinone D (?10.25 kcal/mol: Garcinia Mangostana), Caledol (?10.14 kcal/mol: Calophyllum Caledonicum), Jacareubin (?9.82 kcal/mol: Calophyllum Brasiliensis), γ-mangostin (?9.79 kcal/mol: Garcinia Mangostana) and 2-deprenylrheedia xanthone (?9.64 kcal/mol: Hypericum Roperanum) as good inhibitors of GlcN-6-P among a large set of natural xanthones. And also, most of xanthones have greater binding ability than the compared antifungal drugs. The effect of substituents on binding energy have also been investigated. A detailed analysis of drug likeness for 50 xanthones were also performed and found that most of the xanthone derivatives falls under the category of drug templates.     

Oxidation with a “Stopover” – Stable Zwitterions as Intermediates in the Oxidation of α-Tocopherol (Vitamin E) Model Compounds to their Corresponding ortho-Quinone Methides

As a prominent member of the vitamin E group, α-tocopherol is an important lipophilic antioxidant. It has a special oxidation chemistry that involves phenoxyl radicals, quinones and quinone methides. During the oxidation to the ortho-quinone methide, an intermediary zwitterion is formed. This aromatic intermediate turns into the quinone methide by simply rotating the initially oxidized, exocyclic methyl group into the molecule's plane. This initial zwitterionic intermediate and the quinone methide are not resonance structures but individual species, whose distinct electronic structures are separated by a mere 90° bond rotation. In this work, we hindered this crucial rotation, by substituting the affected methyl group with alkyl or phenyl groups. The alkyl groups slowed down the conversion to the quinone methide by 18-times, while the phenyl substituents, which additionally stabilize the zwitterion electronically, completely halted the conversion to the quinone methide at −78 °C, allowing for the first time the direct observation of a tocopherol-derived zwitterion. Employing a ¹³C-labeled model, the individual steps of the oxidation sequence could be observed directly by NMR, and the activation energy for the rotation could be estimated to be approximately 2.8 kcal/mol. Reaction rates were solvent dependent, with polar solvents exerting a stabilizing effect on the zwitterion. The observed effects confirmed the central relevance of the rotation step in the change from the aromatic to the quinoid state and allowed a more detailed examination of the oxidation behavior of tocopherol. The concept that a simple bond rotation can be used to switch between an aromatic and an anti-aromatic structure could find its use in molecular switches or molecular engines, driven by the specific absorption of external energy.     

Application of Dried Blood Spots and Serum Samples for the Determination of Vitamin D Metabolites in the Group of Healthy Women and with Hashimoto’s Thyroiditis

Chromatographia - The relationship between Hashimoto's thyroiditis and vitamin D concentration was already presented in many studies. The aim of this study was to analyze the differences in the...     

Preparation of Monolithic Column and Its Application in p-CEC

A novel monolithic stationary phase having long alkyl chain ligands was introduced and evaluated in pressurized-capillary electrochromatography of small neutral and charged compounds.The monolithic column was prepared by the in situ copolymerization of ethylene dimethacrylate,1-hexadecene,allyl alcohol and 2-acrylamido-2-methyl-l-propanesulfonic acid in a quaternary porogenic solvent mixture consisting of 1,4-butanediol,cyclohexanol,dodecanol and water.     

Application of organic selenides and tellurides in organic synthesis

This paper describes the progress on the synthesis of organic selenides and tellurides and their application in organic synthesis.Low valent selenium and telluronium compounds having high reducing selectivity can be used to form carbon-hydrogen bonds as special reducing reagents.Telluronium ylides can react with aldehydes and ketones by Wittig-type condensation to produce (E)-configuration alkenes stereoselectively.α-Phenylselanyl arsonium ylides were prepared by transyl-idation reaction of arsonium ylides with phenylselanyl halides which can undergo Wittig-type reactions with carbonyl compounds to give (Z)-α-selanyl-α,β-unsaturated compounds with high stereoselectiv-ity.Zirconium,tin,boron,halogen,metal or hetero-atom were introduced in organoselenium and telluronium compounds as new difunctional group reagents.Under transition metal catalysis,the corresponding cross coupling reactions provide new methods of formation of carbon-carbon double bonds,which were used in the stereoselective synthesis of     

Application of IATA – A case study in evaluating the global and local performance of a Bayesian network model for skin sensitization

The information characterizing key events in an Adverse Outcome Pathway (AOP) can be generated from in silico, in chemico, in vitro and in vivo approaches. Integration of this information and interpretation for decision making are known as integrated approaches to testing and assessment (IATA). One such IATA was published by Jaworska et al., which describes a Bayesian network model known as ITS-2. The current work evaluated the performance of ITS-2 using a stratified cross-validation approach. We also characterized the impact of replacing the most significant component of the network, output from the expert system TIMES-SS, with structural alert information from the OECD Toolbox and Toxtree. Lack of structural alerts or TIMES-SS predictions yielded a sensitization potential prediction of 79%. If the TIMES-SS prediction was replaced by a structural alert indicator, the network predictivity increased up to 87%. The original network’s predictivity was 89%. The local applicability domain of the original ITS-2 network was also evaluated using reaction mechanistic domains to understand what types of chemicals ITS-2 was able to make the best predictions for. We found that the original network was successful at predicting which chemicals would be sensitizers, but not at predicting their potency.