Studies on Antifungal Agents. Part 22. 3-aryl-5-[(aryloxy)alkyl]-3-[(1H-imidazol-1-yl)methyl]-2-methylisoxazolidines and related derivatives

The synthesis and antifungal activity of a novel series of 3-aryl-5-[(aryloxy)alkyl]-3-[(1H-imidazol-1-yl)-methyl]-2-methylisoxazolidines and related compounds, are discussed. The synthesis of the title compounds was accomplished via a 1,3-dipolar cycloaddition of α-substituted ketonitrones with l-alkenyl phenyl ethers (Scheme 2 and 3). The compounds were evaluated for in vitro antifungal activity in solid agar cultures against a broad variety of yeast and systemic mycoses and dermatophytes. While antifungal activity was evident throughout the series, in general, derivatives having halogen atom(s) in either or both aryl rings demonstrated the highest potency, especially against Trichophyton rubrum and Candida albicans. The dichloro analog 20 (PR 967-248) was found to possess the most useful activity. Its minimum inhibitory concentration (MIC) values ranged between 0.2 and 2.0 μg/ml, as compared to 0.2–20.0 μg/ml for the standard drug ketoconazole (4).     

The determination of the gamma isomer content of hexachlorcyclohexane dipwashes

The gamma BHC content of dipwashes has been deterimined satisfactorily by a cryoscopic method. The dipwash is treated with chromic acid to precipitate the total BHC and to destroy much of the organic impurity. Portions of the isolated impure BHC arc dissolved in both benzene and pure gamma BHC. By measurement of the resultant freezing point depression of the solvents, the proportion of gamma isomer in tho original sample can be calculated. The principle of the method should be applicable to other systems where the determination of one component in a multi-component mixture is required.     

Studies on Antifungal Agents. Part 25. 1-[(3,5-Bisaryl-2-methylisoxazolidin-3-yl)methyl]-1H-1,2,4-triazoles

The synthesis and antifungal activity of a novel series of 1-[(3,5-bisaryl-2-methylisoxazolidin-3-yl)methyl]-1H-1,2,4-triazoles 6 and 7 (i.e. 8 – 19 ) are discussed. The preparation of 8 – 19 was straightforward and highlighted by a regiospecific 1,3-dipolar cycloaddition of α-substituted (E)-ketonitrones 4 with appropriate atyrene derivatives 5 that led to a cis/trans-diastereoisomeric mixture of the corresponding triazoles (Scheme). The title compounds were evaluated for in vitro antifungal activity in solid agar cultures against a broad array of yeast and systemic mycoses and dermatophytes. The in vivo activity was determined in an immune-compromised mouse model of systemic candidiasis. While the in vitro activity was evident throughout the series, it was moderate in potency. However, some of the triazole derivatives demonstrated a potent in vivo activity comparable to that of the standard drug ketoconazole. Analogue 12 (PR 988-399) emerged as the best overall compound demonstrating potent antifungal activity in both in vitro and in vivo assays.     

Low temperature NH(X 3sigma-) radical reactions with NO, saturated, and unsaturated hydrocarbons studied in a pulsed supersonic laval nozzle flow reactor between 53 and 188 K

The reactions of ground-state imidogen radicals (NH(X 3sigma-)) with NO and select saturated and unsaturated hydrocarbons have been measured in a pulsed supersonic expansion Laval nozzle flow reactor in the temperature range 53-188 K. The rate coefficients for the NH + NO system display negative temperature dependence in the temperature regime currently investigated and a global temperature-dependent fit is best represented in a modified power law functional form, with k1(NH + NO) = (4.11 +/- 0.31) x 10(-11) x (T/300)(-0.30+/-0.17) x exp(77+/-21/T) cm3/s. The reactions of NH with ethylene, acetylene, propene, and diacetylene were measured over the temperature range 53-135 K. In addition, the reactions of NH with methane and ethane were also measured at 53 K, for reasons discussed later. The temperature dependence of the reactions of NH with the unsaturated hydrocarbons are fit using power law expressions, k(T) = A(T/300)(-n), and are as follows: k4 = (2.3 +/- 1.2) x 10(-12) x (T/300)(-1.09+/-0.33) cm3/s, k5 = (4.5 +/- 0.3) x 10(-12) x (T/300)(-1.07+/-0.04) cm3/s, k6 = (5.6 +/- 1.9) x 10(-12) x (T/300)(-1.23+/-0.21) cm3/s, and k7 = (7.4 +/- 1.8) x 10(-12) x (T/300)(-1.23+/-0.15) cm3/s for ethylene, acetylene, propene, and diacetylene, respectively. The rate for NH + ethane at 53 K is measured to be k3 = (6.8 +/- 1.7) x 10(-12) cm3/s, while that for methane at the same temperature represents an upper bound of k2 < or = (1.1 +/- 4.3) x 10(-12) cm3/s, as this is at the limits of measurement with our current technique. The behavior of these systems throughout the temperature range explored indicates that these reactions occur over a potential energy surface without an appreciable barrier through a complex formation mechanism. Implications for chemistry in low temperature environments where these species are found are briefly discussed.     

Single-shot Thomson scattering on argon plasmas created by the Microwave Plasma Torch; evidence for a new plasma class

To determine the fine-structure size of plasmas created by a Microwave Plasma Torch (MPT), single-shot Thomson scattering (TS) measurements were performed. The aim was to find a solution for the long-standing discrepancy between experiments and Global Plasma Models (GPMs). Since these GPMs are based on the assumption that (ambipolar) diffusion is the main loss process for charged particles, the diffusion length and thus the fine-structure size should be known with high precision before an appropriate theory-experiment comparison can be carried out. In order to avoid the effect of blurring, which is created during the accumulation of multi-shot TS signals and which obscures the fine-structures, single-shot measurements are indispensable to determine the diffusion length.     

Synthesis and structural characterization of hexa-tert-butyl-hexa-peri-hexabenzocoronene, its radical cation salt and its tricarbonylchromium complex

The hexa-tert-butyl substituted hexa-peri-hexabenzocoronene was synthesized in an overall yield of 83% from 4-tert-butylphenylacetylene. The key step was the oxidative cyclodehydrogenation of hexa(4-tert-butylphenyl)benzene with anhydrous FeCl3 in CH2Cl2 The high solubility of hexa-tert-butyl-hexa-peri-hexabenzocoronene in common organic solvents allowed a comprehensive spectroscopic characterization of this compound in solution. Electrochemical oxidation at -30 degrees C in the presence of tetrabutylammonium hexafluoroarsenate led to the formation of a stable radical cation salt. Reaction of hexa-tert-butyl-hexa-peri-hexabenzocoronene with an excess of tricarbonyl(naphthalene)chromium in THF/dioxane afforded a mixture of mono- and bis-tricarbonylchromium complexes which could be separated by chromatography. The molecular structures of the parent compound, its radical cation salt and its mono- tricarbonylchromium complex were determined by X-ray analysis and discussed in detail. Remarkably, the crystal structures of these compounds are mainly dominated by the formation of dimers of the aromatic cores.     

Trithiacyclononane as a ligand for potential technetium and rhenium radiopharmaceuticals: synthesis of [M(9S3)(SC2H4SC2H4S)][BF4] (M = 99Tc, Re, 188Re) via C-S bond cleavage

Chemical or electrochemical reduction of the 1,4,7-trithiacyclononane (9S3) complexes [MII(9S3)2][BF4]2 (M = Re (3a) or Tc (3b)) results in instantaneous C-S bond cleavage to yield ethene and the stable MIII thiolate complexes [MIII(9S3)L][BF4] (M = Re (4a) or Tc (4b), L = SCH2CH2SCH2CH2S). Compounds 4 have been characterized by 1H NMR spectroscopy, and the pseudo-octahedral geometry of 4b has been confirmed by X-ray crystallography. Upon electrochemical reduction 4a loses ethene, while 4b can be reversibly reduced to [TcII(9S3)L], which is then further reduced to Tc(I) with loss of ethene. Successive ethene loss is observed in the mass spectra of compounds 3 and 4. The radiosynthesis of 4a with 188Re can be comfortably completed within 10 min starting with 188ReO4- from a 188W/188Re generator, with a radiochemical yield in excess of 90%, and thus represents a practical approach to the preparation of stable 188Re (and 99mTc) thioether complex derivatives/conjugates for clinical use. Crystal data: 4b, C10H20S6Tc, orthorhombic Pbca, a = 12.233(2) A, b = 14.341(2) A, c = 20.726(3) A, Z = 8.     

Mössbauer spectra obtained by modulation of a scattering crystal

We have carried out numerous experiments with supersources having intensities in the 100 Curie range. These sources usually require massive shielding, and are not easily moved to carry out Mössbauer spectroscopy. Several of these sources can be used with microfoil conversion electron (MICE) detectors, but they cannot be moved easily either because of the delicate microfoils used, which ideally have thicknesses less than the range of the internally converted electrons. Here, we describe a technique for doing Mössbauer spectroscopy by oscillating a monochromating crystal parallel to the reciprocal lattice vector of the Bragg reflection, this being used to filter out extraneous photons from the beam. Specifically, an LiF crystal is used in diffraction experiments as a filter to scatter the 46.5-keV Mössbauer gamma rays from¹⁸³Ta by setting it at the (200) Bragg reflection. In the present measurements, the LiF crystal was mounted in the transmission mode and oscillated with a crank along the scattering vectorQ to produce the velocity modulation, with the source, sample and absorber all at rest. The velocity components of the filtering crystal along the incident and scattered beams cause the measured linewidth to be equal to the usual Mössbauer width divided by 2 sin, where is the Bragg angle. Measured widths for the (200), (400), (600) and (800) Bragg reflections agreed with the calculated values of 12.08, 6.04, 4.03 and 3.02 cm/s, within our experimental uncertainties. The technique could have applications not only to MICE detectors, but also to very narrow resonances such as⁶⁷Zn, where the increased velocities required for small Bragg angles could be an advantage and lead to enhanced resolution.     

An active spectroscopical study on the plasma parameters of an ICP

Various techniques to measure the electron density and temperature of a 100 MHz inductively coupled plasma (ICP) are compared with each other. Apart from passive spectroscopy of measuring the shape of (e.g. H(beta)) and the area under emission lines we explored the field of active spectroscopy. Non-intrusive and specific are the methods of diode laser absorption (DLA) of an argon 4s-4p transition and Thomson scattering (TS). Intrusive and global is the power interruption (PI) technique: the response of line (argon and analytes) and continuum emission is followed during PI. Finally, a combination of two active techniques, namely TS during PI, is studied. By using the different techniques on the same plasma condition (frequency, power and flows) this intercomparison will reveal the validity region of the various techniques. In this way a strong basis will be created for understanding plasma phenomena.