J. Appl. Cryst.の発刊に際して

Adequate initial configurations for molecular dynamics simulations consist of arrangements of molecules distributed in space in such a way to approximately represent the system's overall structure. In order that the simulations are not disrupted by large van der Waals repulsive interactions, atoms from different molecules must keep safe pairwise distances. Obtaining such a molecular arrangement can be considered a packing problem: Each type molecule must satisfy spatial constraints related to the geometry of the system, and the distance between atoms of different molecules must be greater than some specified tolerance. We have developed a code able to pack millions of atoms, grouped in arbitrarily complex molecules, inside a variety of three-dimensional regions. The regions may be intersections of spheres, ellipses, cylinders, planes, or boxes. The user must provide only the structure of one molecule of each type and the geometrical constraints that each type of molecule must satisfy. Building complex mixtures, interfaces, solvating biomolecules in water, other solvents, or mixtures of solvents, is straightforward. In addition, different atoms belonging to the same molecule may also be restricted to different spatial regions, in such a way that more ordered molecular arrangements can be built, as micelles, lipid double-layers, etc. The packing time for state-of-the-art molecular dynamics systems varies from a few seconds to a few minutes in a personal computer. The input files are simple and currently compatible with PDB, Tinker, Molden, or Moldy coordinate files. The package is distributed as free software and can be downloaded from http://www.ime.unicamp.br/~martinez/packmol/.

/pdf/packmol-a-package-for-building-initial-configurations-for-qsy9r74wrw.pdf

PACKMOL: a package for building initial configurations for molecular dynamics simulations.

基礎講座 電気泳動(Electrophoresis)

It is important that the medical profession plays a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.

Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular tests or therapies are considered as well as frequency of follow-up and cost effectiveness. When available, information from studies on cost will be considered; however, review …

/pdf/acc-aha-esc-2006-guidelines-for-management-of-patients-with-5a3f1emfzy.pdf

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

The concept of metabolite profiling has been around for decades, but technical innovations are now enabling it to be carried out on a large scale with respect to the number of both metabolites measured and experiments carried out. Here we provide a detailed protocol for gas chromatography mass spectrometry (GC-MS)-based metabolite profiling that offers a good balance of sensitivity and reliability, being considerably more sensitive than NMR and more robust than liquid chromatography-linked mass spectrometry. We summarize all steps from collecting plant material and sample handling to derivatization procedures, instrumentation settings and evaluating the resultant chromatograms. We also define the contribution of GC-MS-based metabolite profiling to the fields of diagnostics, gene annotation and systems biology. Using the protocol described here facilitates routine determination of the relative levels of 300-500 analytes of polar and nonpolar extracts in approximately 400 experimental samples per week per machine.

Gas chromatography mass spectrometry–based metabolite profiling in plants

1H and 13C NMR data for 1-cyano-, 4-cyano-, 4-bromo- and 4-bromo-5-nitro-substituted isoquinolines, isoquinoline N-oxides and N-methoxy and N-ethyl salts in different solvents are reported. The substituent chemical shifts are discussed with regard to the reactivity of the N-methoxy compounds in the presence of nucleophilic reagents.

1H and 13C NMR studies of substituted isoquinolinium derivatives in different solvents

Allosteric Ligands for G Protein‐Coupled Receptors: A Novel Strategy with Attractive Therapeutic Opportunities

Der 3,11-dipyridylsubstituierte 5-Oxo-2,6-methano-2-benzazocin-6-carbonsaureester 1 wird mit Grignard- bzw. lithiumorganischen Reagentien zu tertiaren Alkoholen umgesetzt. Auf diesem Wege gelingt die stereoselektive Einfuhrung von Methyl-, Phenyl-, Propargyl- und Ethinylsubstituenten an C-5 des Methanobenzazocingerustes. Die Aufklarung der relativen Konfiguration der so erhaltenen Alkohole erfolgt mit Hilfe der 1H- und 13C-NMR-Spektroskopie.



Stereoselective Syntheses at tertiary 2,6-Methano-2-benzazocin-5-oles



The conversion of the 3,11-dipyridine substituted methyl 5-hydroxy-2,6-methano-2-benzazocine-6-carboxylates 1 with Grignard- and lithium organic compounds stereoselectively yields tertiary alcohols with methyl-, phenyl-, propargyl- and ethinylsubstituents at C-5. The relative configuration of the alcohols so obtained is determined by means of 1H-NMR and 13C-NMR spektroscopic data.

Stereoselektive Synthese tertiärer 2,6‐Methano‐2‐benzazocin‐5‐ole

The temperature and concentration dependence of the 1 H NMR spectra of four anilinomethylenemalonic acid derivatives were determined in CDCl 3 and DMSO-d 6 to assign the E-Z isomers and to investigated the formation of intra- and intermolecular hydrogen bonds. Chemical shifts and coupling constant in the 13 C NMR spectra correspond with the results of the 1 H NMR investigations in the case of the cyanoacetate ester derivative. Contradictory results for the acetoacetate derivative were found by semi-empirical calculations

E–Z isomerism of anilinomethylenemalonic acid derivatives

Pyrimethamine is an important antiparasitic drug in the treatment of malaria and toxoplasmosis and is often used in combination with either sulfadoxine, sulfalene, or sulfadiazine. Determining the content of pyrimethamine and investigating the related substances is currently possible applying either a compendial monograph utilizing thin layer chromatography as well as liquid chromatographic methods used by the respective manufacturers. To provide a simple method which is capable of determining the content of pyrimethamine and of resolving four of its potential synthetic impurities a very simple, cheap, precise, and accurate isocratic RP-HPLC method was developed. All analytes can be separated within a total runtime of 30 min and the method was linear within the concentration ranges of 0.12–0.740, 0.104–0.621, 0.120–0.710, 2.0–11.8, and 1.01–5.80 µg mL−1 for pyrimethamine, impurity A, impurity B, impurity C, and impurity D, respectively. These substances were separated by employing a Eurospher-II C18H column (250 × 4.6 mm, 5 µm particle size), a mobile phase being a mixture of a 0.05 M KH2PO4 buffer solution (pH 2.6) and methanol in the ratio 40:60 (v/v). The analysis was carried out at 30 °C, applying a flow rate of 1.2 mL min−1, and a detection wavelength of λ = 215 nm. The coefficients of determinations (R
 2) for the five analytes were greater than 0.994 for pyrimethamine and all impurities. Results of recovery studies were within the range of 89.1–105.1% for all substances. In all tested genuine batches of pyrimethamine raw material impurities within the specified limits were present which is concurrent with results obtained from using the present manufacturer’s method.

Development of a Simple, Rapid, and Robust Isocratic Liquid Chromatographic Method for the Determination of Pyrimethamine and its Synthetic Impurities in Bulk Drugs and Pharmaceutical Formulations

Ulrike Holzgrabe

Papers

1H and 13C NMR studies of substituted isoquinolinium derivatives in different solvents

Allosteric Ligands for G Protein‐Coupled Receptors: A Novel Strategy with Attractive Therapeutic Opportunities

Stereoselektive Synthese tertiärer 2,6‐Methano‐2‐benzazocin‐5‐ole

E–Z isomerism of anilinomethylenemalonic acid derivatives

Development of a Simple, Rapid, and Robust Isocratic Liquid Chromatographic Method for the Determination of Pyrimethamine and its Synthetic Impurities in Bulk Drugs and Pharmaceutical Formulations