Transfer of near-infrared monochromator calibrations for tobacco constituents to tilting-filter instruments

Near-infrared calibrations for water, reducing sugar, glycerin, propylene glycol, nicotine, and menthol in tobacco blends were first obtained with a monochromator instrument. Transfer of calibrations to a tilting-filter instrument for factory trials is shown to be facilitated greatly by the computer-assisted scheme MTRAN. By means of this software, calibration equations were established for a Neotec 51A instrument that is sufficiently rugged for factory use. The predictive capabilities of the transferred calibrations are similar to those of the research monochromator.     

A 3D QSAR pharmacophore model and quantum chemical structure--activity analysis of chloroquine(CQ)-resistance reversal

Using CATALYST, a three-dimensional QSAR pharmacophore model for chloroquine(CQ)-resistance reversal was developed from a training set of 17 compounds. These included imipramine (1), desipramine (2), and 15 of their analogues (3-17), some of which fully reversed CQ-resistance, while others were without effect. The generated pharmacophore model indicates that two aromatic hydrophobic interaction sites on the tricyclic ring and a hydrogen bond acceptor (lipid) site at the side chain, preferably on a nitrogen atom, are necessary for potent activity. Stereoelectronic properties calculated by using AM1 semiempirical calculations were consistent with the model, particularly the electrostatic potential profiles characterized by a localized negative potential region by the side chain nitrogen atom and a large region covering the aromatic ring. The calculated data further revealed that aminoalkyl substitution at the N5-position of the heterocycle and a secondary or tertiary aliphatic aminoalkyl nitrogen atom with a two or three carbon bridge to the heteroaromatic nitrogen (N5) are required for potent "resistance reversal activity". Lowest energy conformers for 1-17 were determined and optimized to afford stereoelectronic properties such as molecular orbital energies, electrostatic potentials, atomic charges, proton affinities, octanol-water partition coefficients (log P), and structural parameters. For 1-17, fairly good correlation exists between resistance reversal activity and intrinsic basicity of the nitrogen atom at the tricyclic ring system, frontier orbital energies, and lipophilicity. Significantly, nine out of 11 of a group of structurally diverse CQ-resistance reversal agents mapped very well on the 3D QSAR pharmacophore model.     

Synthesis,Structure, and Antimalarial Activity of Tricyclic 1,2,4-Trioxanes Related to Artemisinin

Two sets of tricyclic 1,2,4-trioxanes containing the ABC ( 10 , 11 ) and ACD ring portions ( 21 , 22 , 32 , 33 , 37 , and 38 ) of artemisinin ( 1 ) were synthesized by successive photo-oxygenation of appropriate enol-ether precursors to 1,2-dioxanes and inter- and intramolecular reaction with a carbonyl compound or oxo-substituted side-chain. The structures of 10 , 21 , and 22 were determined by X-ray analysis. The anti-malarial activity of all trioxanes, except 37 and 38 , was evaluated in vitro against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum parasites. Trioxanes 11 and 21 were as active as artemisinin ( 1 ). It was found that neither the lactone function nor rings B and D of 1 were essential for activity. A possible pharmacophore for artemisinin-like activity, which embodies a spirocyclopentane group attached to C(3) of 1,2,4-trioxane, was proposed.     

On the kinematics of 2+1-dimensional motions of a fibre-reinforced fluid. Integrable connections

Evolution of foliations of the plane is shown, under a conditionof constant divergence, to be linked to the scattering problemfor the integrable modified Korteweg–de Vries hierarchy.This result is applied to a set of kinematic relations whicharise in the theory of ideal fibre-reinforced fluids. In particular,it is established that the fibres, which are convected withthe fluid, constitute generalized tractrices.     

Synthesis and antimalarial activities of structurally simplified 1,2,4-trioxanes related to artemisinin

Eleven derivatives of the clinically useful, antimalarial, 1,2,4-trioxane artemisinin have been synthesized in only several steps from commercial cyclohexanones. Of these simple, tricyclic 1,2,4-trioxanes, 10 showed considerable in vitro antimalarial activity, with one being as potent as artemisinin. Some structure-activity relationship generalizations are made from this series of artemisinin analogs. Triethylsilyl hydrotrioxide (Et₃SiOOOH), prepared in situ from ozone and triethylsilane, is shown to be a mild, fastacting, and effective dioxetane-forming reagent with vinyl ethers and with a vinyl thioether on relatively small (50–100 mg) scale.