Heats of melting of sodium nitrate and indium by differential scanning calorimetry: a suggestion for a new calibration substance

Measurments with a Perkin-Elmer DSC-2 differential scanning calorimeter that has been calibrated with indium, tin, and lead have yielded values for the heat of melting of sodium nitrate. Analysis of these results along with those from earlier investigations gives ΔH_m ? 3615 cal mol^?1 as a recommended “best” value for the heat of melting of NaNO₃. The consistency of our results over a period of three years in which many samples were investigated, in combination with results of earlier investigations, leads us to suggest that NaNO₃ is a useful substance for calibration of differential scanning calorimeters. Results of our measurements of the heat of melting of indium are presented and discussed in relation to earlier investigations.     

Unsymmetrical Diarylketones from Electron-rich Heterocyclic Arenes

Summary.  AlCl₃-mediated chlorocarbonylation of a first arene by oxalyl chloride followed by in situ Friedel-Crafts acylation of a second electron-rich arene expeditiously provides, in a one-pot procedure, either symmetrical or unsymmetrical benzophenones with yields ranging from 17–52%. Best results are obtained when the more activated substrate is used as the second arene. Another advantage is that the resultant benzophenone precipitates from the reaction mixture allowing facile workup. Corresponding author. E-mail: Poupaert@cmfa.ucl.ac.be Received October 4, 2002; accepted October 15, 2002 Published online March 6, 2003     

PIC code simulation of pulsed radiation in a tapered closed-cavitygyrotron

MAGIC, a two-and-one-half-dimensional particle-in-cell (PIC) code, has been used to investigate mode locking in closed-cavity gyrotrons. A cavity, with equally spaced modal frequencies, composed of a radially tapered section and a straight section of waveguide, is designed, built, and cold-tested. Experimental cold test results agree well with the MAGIC PIC code simulations. Using a sinusoidal current density modulation with an amplitude of 5% of the dc current and frequency of 280 MHz, the simulation results show radiation output in a train of narrow pulses (full width at half maximum ~1 us) at a 280 MHz repetition rate. Though the gyrotron does not appear to be mode locked, uniform pulse trains of 30-50 pulses can be obtained     

On the possibility of analytically continuing stabilization graphs to determine resonance positions and widths accurately

Previous efforts to extract resonance widths by analytic continuation of stabilization graphs were limited by non-analytic behavior of the eigenvalues as functions of the stabilization parameter. We describe a procedure which avoids this difficulty by numerical analytic continuation of the characteristic polynomial, truncated to low order, of the hamiltonian matrix.     

Investigation of phenolic bioisosterism in opiates: 3-sulfonamido analogues of naltrexone and oxymorphone

[formula: see text] The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. On the basis of its putative role as a hydrogen-bonding donor in the interaction with opioid receptors, it was replaced with a sulfonamide group because of their similar pKa values. The first thebaine-derived 3-amino (8a, 8b) and subsequent sulfonamide analogues (10a, 10b) were synthesized from naltrexone (1a) and oxymorphone (1b) in a linear nine-step synthesis. The sulfonamides were tested in vitro and found inactive.     

Toward <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> DXR inhibitor design: homology modeling and molecular dynamics simulations

Mycobacterium tuberculosis 1-deoxy-d-xylulose-5-phosphate reductoisomerase (MtDXR) is a potential target for antitubercular chemotherapy. In the absence of its crystallographic structure, our aim was to develop a structural model of MtDXR. This will allow us to gain early insight into the structure and function of the enzyme and its likely binding to ligands and cofactors and thus, facilitate structure-based inhibitor design. To achieve this goal, initial models of MtDXR were generated using MODELER. The best quality model was refined using a series of minimizations and molecular dynamics simulations. A protein–ligand complex was also developed from the initial homology model of the target protein by including information about the known ligand as spatial restraints and optimizing the mutual interactions between the ligand and the binding site. The final model was evaluated on the basis of its ability to explain several site-directed mutagenesis data. Furthermore, a comparison of the homology model with the X-ray structure published in the final stages of the project shows excellent agreement and validates the approach. The knowledge gained from the current study should prove useful in the design and development of inhibitors as potential novel therapeutic agents against tuberculosis by either de novo drug design or virtual screening of large chemical databases. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Simple, Sensitive, High-Throughput Method for the Quantification of Mitragynine in Rat Plasma Using UPLC-MS and Its Application to an Intravenous Pharmacokinetic Study

A simple, sensitive and rapid ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method was developed and validated for the quantification of mitragynine in rat plasma using amitriptyline hydrochloride as an internal standard. Sample preparation involved a one-step liquid?Cliquid extraction using methyl t-butyl ether. Mitragynine was separated on an Acquity UPLC^? BEH HILIC column using isocratic elution with a mobile phase of 10 mM ammonium formate buffer containing 0.1% formic acid:acetonitrile (15:85, v/v). At a flow rate of 0.2 mL min^?1, the retention time of mitragynine was found to be 1.3 min. Ionization was performed in the positive ion electrospray mode. The selected mass-to-charge (m/z) ratio transition of mitragynine ion [M + H]⁺ used in the selected ion recording (SIR) was 399.1. The calibration curve was found to be linear over a concentration range of 1?C5,000 ng mL^?1 (r = 0.999) with a lower limit of quantification (LLOQ) of 1 ng mL^?1. Intra- and inter-day assay variations were found to be less than 15%. The extraction recoveries ranged from 85?C93% at the three concentrations (2, 400 and 4,000 ng mL^?1) in rat plasma. This method was successfully used to quantify mitragynine in rat plasma following intravenous administration of the compound.