Simple tests for density functional methods

The performance of the currently used generalized gradient approximation density functionals is analyzed using several simple, yet critical requirements. We analyze the effects of the self-interaction error, the inclusion of the exact exchange, and the parameter settings used in the popular three-parameter hybrid density functionals. The results show that the elimination of the self-interaction error from the current density functionals lead to very poor results for H₂. The inclusion of the exact exchange does not significantly influence the self-interaction corrected results. The variation of the A, B, and C parameters of a hybrid DFT method influences the H(SINGLE BOND)H equilibrium bond length through a very simple linear equation, and it is possible to reproduce the experimental H(SINGLE BOND)H distance with appropriate selection of these parameters, although an infinite number of solutions exists. Similar results were obtained for the total energy and the electron density along the internuclear axis. The analysis of the exact KS potential at the bond critical point of the dissociating H₂ molecule shows that, for this property, the second order Moller–Plesset perturbation theory yields a better potential than the density functionals studied in this article. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1534–1545, 1997     

3D QSAR methods: Phase and Catalyst compared

The programs Phase and Catalyst HypoGen are compared for their performance in determining three-dimensional quantitative structure-activity relationships. Eight sets of compounds with measured activity were collected from the public literature and partitioned into suitable training and test sets by an automated procedure. A range of models is built with each program, and suggested parameter variations are investigated. The models are assessed by their ability to predict the activity of compounds in the test set, and it is demonstrated that the performance of Phase is better than or equal to that of Catalyst HypoGen, with the data sets and parameters used here. Additionally, compounds in two of the data sets are overlaid on crystallographic structures of similar ligands in complex with the target receptor, in order to guide pharmacophore generation by the two programs, but the resulting models do not perform better.     

Reproducibility estimates from single-laboratory ruggedness tests compared with those derived from collaborative trials of six microbiological measurement methods

This work investigated the feasibility of single-laboratory ruggedness experiments to estimate between-laboratory reproducibility. Six microbiological measurement methods that had already been subject to multi-laboratory validation were studied. Ruggedness experiments were designed and executed to determine sensitivity coefficients for factors judged likely to vary between laboratories. These were combined with estimates of factor variation to give reproducibility estimates. The single-laboratory estimates of reproducibility were generally not similar to those generated from multi-laboratory work. The experimental plans were difficult to design and execute, and were only partially successful in producing useful sensitivity coefficients. The authors conclude that ruggedness tests do not offer a single-laboratory alternative to multi-laboratory method validation or a practical approach to the evaluation of measurement uncertainty for microbiological methods. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Campden BRI was previously known as the Campden and Chorleywood Food Research Association.     

Elastohydrodynamic Collision of Two Spheres Allowing Slip on Their Surfaces

Our goal is to study theoretically the effect of deformation on the collision of two solid spheres allowing slip on their surfaces. The deformed shape of the solid surface is determined via an asymptotic technique assuming that deformation is small compared with the separation between the surfaces. It has previously been shown that the slippage makes collision possible even without any surface attractive force. Here we demonstrate that even a small amount of deformation can preclude spheres from coagulation. Copyright 2000 Academic Press.     

Two methods for direct ortho-arylation of benzoic acids

Two new palladium-catalyzed methods for the direct ortho-arylation of free benzoic acids have been developed. The first method employs stoichiometric silver acetate for iodide removal, aryl iodide as the coupling partner, and acetic acid solvent. This method is applicable to the arylation of electron-rich to moderately electron-poor benzoic acids and tolerates chloride and bromide substituents on both coupling partners. The second method involves the use of aryl chloride, cesium carbonate base, n-butyl-di-1-adamantylphosphine ligand, and DMF solvent and is suitable for both electron-rich and electron-poor benzoic acids. Mechanistic studies of the second method point to the heterolytic C-H bond cleavage as the rate-determining step.     

Two new measurement methods for determining TN structure

A TN structure is characterized by a twist angle (Theta) and a Deltand value, where Deltan is the refractive index anisotropy value of a liquid crystal material and d is the TN cell gap value. Two new methods for measuring these values have been proposed. One is to determine only the Deltand value by rotating the TN cell for a known Theta value. The other is to determine the Deltand value and the Theta value by rotating the analyser. After analysing these measurement methods, the Deltand value, or the Deltand value and Theta can be determined graphically. These methods can easily be applied to automatic measurement systems.     

Two new methods for the synthesis of C-glycosides

Thiophenyl glycosides are converted to C-glycosides by reaction with allyl or methallyltri-$\text{n}$-butylstannane using both “one-electron” and “two-electron” procedures, which give different stereoselectivities in some cases.     

Requirements and tests for HPLC apparatus and methods in pharmaceutical quality control

Summary One possible method has been demonstrated for pharmaceutical quality control which is not restricted to this field and fulfils and documents the prerequisites for reliable, accurate and precise HPLC analysis. This includes validation which shows that the method is able in principle to fulfil the requirements, the apparatus test which shows that the apparatus generally works correctly and precisely and the system suitability test which shows that the method provides accurate and precise results on this apparatus and with this column for the analysis in question when other non-equipment and non-method-induced errors are excluded.     

Two methods for the separation of monounsaturated octadecenoic acid isomers

The identification and quantification of complex mixtures of cis and trans octadecenoic (18:1) fatty acid isomers presents a major challenge for conventional one-dimensional GC/FID analysis of their methyl esters. We have compared the use of two methods to achieve optimized separations of positional and geometrical octadecenoic fatty acid isomers—comprehensive two-dimensional gas chromatography (GC × GC), and silver ion high performance liquid chromatography interfaced to atmospheric pressure photoionization (APPI) mass spectrometry. Nine isomers of octadecenoic acid methyl ester were well separated on a single silver ion column with a mobile phase of 0.018% acetonitrile and 0.18% isopropanol in hexane. Reproducible retention times were obtained with relative standard deviations of around 1% over 5 injections. The extra selectivity and reproducibility afforded by APPI-MS, together with the wide separation of cis and trans isomers by silver ion chromatography, resulted in a promising method for measurement of octadecenoic acid FAME. The GC × GC separation was performed using various column combinations, and optimal separation was obtained by coupling an ionic liquid column (Supelco SLB-IL100 [1,9-di(3-vinyl-imidazolium) nonane bis(trifluoromethyl) sulfonyl imidate]) in the first dimension with a SGE BPX50 (50% phenyl polysilphenylene-siloxane) in the second dimension. These methods have been applied to the analysis of octadecenoic acid in milk and beef fat.     

Recovery and sporicidal resistance of various B. subtilis spore preparations on porcelain penicylinders compared with results from AOAC test methods

Sporicidal test results obtained from carriers inoculated with 4 types of defined Bacillus subtilis spore preparations were compared with the standard AOAC sporicidal test using soil extract nutrient broth (SENB) B. subtilis 19659 spores. Recoveries of spores inoculated on penicylinders from B. subtilis clean spores (washed and suspended in water) and B. subtilis 19659 spores inoculated from culture filtrates according to the AOAC method were compared. Spores were exposed to 6 concentrations (0.5-3.0% w/v) of glutaraldehyde in phosphate buffer (pH 7.5) for 10 h. Concentrations were established by titrimetry and liquid chromatography. Recoveries of surviving spores were determined for 3 types of clean B. subtilis var. niger preparations, one clean B. subtilis 19659 preparation, and the SENB B. subtilis 19659 filtrates. Spore carriers, inoculated by the standard AOAC protocol, resulted in as much as a 2-log number difference in runs 1-12, but not more than 0.5 log number for each clean spore preparation. The SENB spores varied most in resistance to glutaraldehyde, with no growth in recovery media from 3 different batches of 1, 1.5, and 2% glutaraldehyde. Separate batches of SENB preparations of B. subtilis 19659 were resistant and destroyed by 1.0% glutaraldehyde, with 3.98 and 6.0 log numbers of spores on penicylinders, respectively. Clean spore preparations of B. subtilis 19659 on porcelain penicylinders were more resistant to glutaraldehyde than were SENB spores. Nutrient agar/Mg/Ca and nutrient agar/Mg spore preparations of B. subtilis var. niger showed the most uniform resistance to glutaraldehyde. Spores with calcium added showed increased resistance to glutaraldehyde. B. subtilis 19659 spores from the Columbia broth spore preparation were the most resistant and were recovered after exposure to 3.0% glutaraldehyde.     

Two methods of describing adsorption equilibrium

The thermodynamics of adsorption equilibrium with a single-component gas phase have been analyzed for two different models of adsorption. It has been shown that with a cell model of adsorption, the differential energy of the adsorbent/adsorbate system is expressed by the same formula as in the other model, in terms of quantities characterizing the equilibrium gas. An expression is derived for the differential energy, with deformation of the adsorbent taken into account. The two methods of calculating the isosteric heat of adsorption are compared.Institute of Physical Chemistry, Russian Academy of Sciences, Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 19–23, January, 1992.     

Cubic splines compared with other methods for the calculation of programmed temperature retention indices

Summary Program temperature retention indices for fifteen nonalkane solutes have been determined by cubic splines, by other procedures found in the literature and by interpolation of the n-alkanes retention time logarithm for eleven temperature programs. A comparison in terms of variance of the differences between PTRI calculated by CS and each of the remaining methods is made for each of the eleven program runs, for each of the three stationary phases used and for many of the programs. The smallest variances obtained result when the Zenkevich, van den Dool & Kratz and Chen et al. methods are tested. The stationary phase polarity is of no relevance since it has no effect on the specific PTRI found by the different methods employed in this work.     

Description and comparison of chromatographic tests and chemometric methods for packed column classification

The main tests developed in last 20 years to investigate the chromatographic behaviour and the stationary phase properties are described in this paper. These properties are the hydrophobicity, depending on the surface area and the bonding density, the number of accessible residual silanol groups having sometimes different acidity, which can interact with neutral solutes by hydrogen bonds or with the ionic form of basic compounds and the shape or steric selectivity, depending on both the functionality of the silanising agent and the bonding density. Two types of tests are performed, either based on key solutes having well defined properties such as phenol, caffeine, amitriptyline, benzylamine, acenaphtene, o-terphenyl, triphenylene, p-ethylaniline, carotenoid pigments, or on retention models (solvation parameter, hydrophobic subtraction) obtained from the analyses of numerous and varied compounds. Thus, the chromatographic properties are either related to selectivities or retention factors calculated from key solutes, or they are described by interaction coefficients provided by multilinear regression from retention models. Three types of comparison methods are used based on these data. First, simple plots allow the study of differences between the columns as regards to one or two properties. Columns located in the same area of the plot display close properties. Second, chemometric methods such as principal component analysis (PCA) or hierarchical cluster analysis (HCA) can be performed to compare columns. In this case, all the studied properties are included in the comparison, done either by data projection to reduce the space in which the information is located (PCA) or by distance calculation and comparison for drawing a classification (HCA). Neighbouring columns are expected to provide identical chromatographic performances. These two chemometric methods can be used together, PCA before HCA. The third way is to calculate a discrimination factor from a reference column, through calculation methods based on the Pythagorean Theorem: the lower this factor, the closer the column properties. Following the presentation of the analytical conditions, the compounds and the data treatments used by the teams working in this field, the pertinence of the different selectivities, i.e. of the different probe solute couples or of the different interaction coefficients, are discussed as regards their discrimination capacity. The accuracy of chemometric treatments in the discrimination of stationary phases having different functionalities (octadecylsiloxane (ODS), cyano, fluorinated, phenyl, polar embedded group or "aqua" type) will be discussed, as well as their performances in the finer ODS discrimination. New two-dimensional plots, from data gained by different studies will be suggested, to improve the classification of stationary phases having different nature of bonded chains.     

Two new graph-theoretical methods for generation of eigenvectors of chemical graphs

Two new graph-theoretical methods, (A) and (B), have been devised for generation of eigenvectors of weighted and unweighted chemical graphs. Both the methods show that not only eigenvalues but also eigenvectors have full combinatorial (graph-theoretical) content. Method (A) expresses eigenvector components in terms of Ulam’s subgraphs of the graph. For degenerate eigenvalues this method fails, but still the expressions developed yield a method for predicting the multiplicities of degenerate eigenvalues in the graph-spectrum. Some well-known results about complete graphs (K _n) and annulenes (C _n ), viz. (i)K _n has an eigenvalue −1 with (n−1)-fold degeneracy and (ii) C _n cannot show more than two-fold degeneracy, can be proved very easily by employing the eigenvector expression developed in method (A). Method (B) expresses the eigenvectors as analytic functions of the eigenvalues using the cofactor approach. This method also fails in the case of degenerate eigenvalues but can be utilised successfully in case of accidental degeneracies by using symmetry-adapted linear combinations. Method (B) has been applied to analyse the trend in charge-transfer absorption maxima of the some molecular complexes and the hyperconjugative HMO parameters of the methyl group have been obtained from this trend.     

Two high-performance liquid chromatographic methods for quantitation of theophylline in plasma

Two high-performance liquid chromatographic methods are described for the assay of theophylline in plasma. Both allowed the separation of theophylline from the caffeine metabolites, theobromine and 1,7-dimethylxanthine. Method A, using 8-chlorotheophylline as internal standard, involved back extraction of theophylline from organic extract with 0.1 M sodium hydroxide. Method B used generally accepted solvent extraction followed by evaporation and beta-hydroxyethyltheophylline as internal standard. High-performance liquid chromatographic analyses were performed on reversed-phase phenyl columns (25 X 0.46 and 25 X 0.41 cm) using 20% methanol in 20 mM phosphate buffer at pH 5.6 for Method A and 2% acetonitrile and 8% methanol in 20 mM phosphate buffer for Method B. The column effluent was monitored at UV 273 nm. Standard curves for both Methods A and B were fitted by linear regression (r greater than 0.999) in the concentration range of 0.05-50 micrograms/ml. Either method was selective, accurate and reproducible over the concentration range 0.08-26 micrograms/ml. However, compared with Method B, Method A provided significant advantages in terms of simplicity, speed and efficiency.     

Two efficient methods for the synthesis of novel indole-based chalcone derivatives

Two powerful methods for the synthesis of indole-based chalcone derivatives, namely (E)-1-(2-chloro-1-(4-chlorobenzyl)-1H-indol-3-yl)-3-aryl(hetaryl)prop-2-en-1-ones (3a–l), are described, involving the ultrasound-assisted or solvent-free Claisen–Schmidt condensation reaction of 3-acetyl-2-chloro-1-(4-chlorobenzyl)indole (1) and various aromatic aldehydes (2a–l). The ultrasound-assisted Claisen–Schmidt condensation reaction was carried out using 1,4-dioxane as solvent and KOH as base at room temperature to give the corresponding products (3a–l) in yields ranging from 75 to 88 %. Alternatively, the Claisen–Schmidt condensation reaction could also be conducted under solvent-free conditions to obtain the products (3a–l) in comparable yields. The two procedures offer easy access to indole-based chalcone derivatives in short reaction times and good yields under mild conditions. Particularly, the advantageous aspect of the solvent-free method could avoid the use of environmentally hazardous and toxic solvents, and also reduced costs. The structures of all the newly synthesized indole-based chalcones 3a–l were confirmed by spectral data and elemental analyses.     

Two quality and stability indicating imaged CIEF methods for mRNA vaccines

Two imaged capillary isoelectric focusing methods were developed to provide insight into the quality and stability of messenger ribonucleic acid (mRNA) vaccines, specifically, mRNA encapsulated in lipid nanoparticles (LNPs). A variety of stressed and lipid composition-modified samples were measured and detected by their UV absorption. The results were supported by the data of an encapsulation assay and particle sizing. One method, using 9 M urea as an additive, shows two broad and jagged peaks in which the peak shape offers detailed information. The summed peak area of both peaks showed RSDs from 2% to 8% when one batch was measured in triplicate and apparently depends on the size of the LNPs. In the second method, a combination of 5.5 M urea and 2 M N-ethylurea was used. This method is characterized by a high repeatability of the isoelectric point (pI, <0.5%). The repeatable peak area (RSD of 2%–7%) correlates linearly with the mRNA content, which also applies to the first method, and added stress is evident by the change in pI and peak area. Furthermore, experiments with the addition of a fluorescent dye were performed (fluorescence detection), which tremendously increased the sensitivity of the methods. Both methods can be used to characterize the stability of mRNA-loaded LNPs, for example, when investigating various storage times at different temperatures and freeze–thaw cycles, as well as the ability of the methods to distinguish lipid compositions and measure batch-to-batch variability.     

Methodology for the validation of analytical methods involved in uniformity of dosage units tests

Validation of analytical methods is required prior to their routine use. In addition, the current implementation of the Quality by Design (QbD) framework in the pharmaceutical industries aims at improving the quality of the end products starting from its early design stage. However, no regulatory guideline or none of the published methodologies to assess method validation propose decision methodologies that effectively take into account the final purpose of developed analytical methods. In this work a solution is proposed for the specific case of validating analytical methods involved in the assessment of the content uniformity or uniformity of dosage units of a batch of pharmaceutical drug products as proposed in the European or US pharmacopoeias. This methodology uses statistical tolerance intervals as decision tools. Moreover it adequately defines the Analytical Target Profile of analytical methods in order to obtain analytical methods that allow to make correct decisions about Content uniformity or uniformity of dosage units with high probability. The applicability of the proposed methodology is further illustrated using an HPLC-UV assay as well as a near infra-red spectrophotometric method.     

Preparation of thermal-enhanced epoxy resin adhesive with organic PCM for applying wood flooring

Epoxy resins are well-known materials that show beneficial properties, such as high tensile strength and modulus, good adhesive properties, low cost, and ease of processing and environmental advantages. However, epoxy resin adhesive has no characteristic of thermal storage. Latent heat storage is one of the favorable kinds of thermal energy storage methods considered for energy saving and thermal efficiency in various fields, such as solar air conditioning systems and buildings. So we prepared thermal-enhanced epoxy resin adhesive by using PCM. This paper addresses the effects of n-hexadecane and sodium lauryl sulfate on the thermal properties and chemical properties of epoxy resin adhesive and HEAC, using differential scanning calorimetry, thermal gravimetric analysis, and Fourier transform-infrared spectroscopy. Also, we evaluated the applicability of composite epoxy resin adhesive to wood-based flooring using n-hexadecane, through measurement of bonding strength from universal testing machine analysis.