Synthesis of penicillin derivatives and study of their cytotoxic properties

By the interaction of heterocyclic thiols with sulfoxides of 6,6-dihydro- and 6-chloropenicillanates, derivatives of 4-heteryldithio-2-azetidinones have been synthesized, as well as products of their cyclization to form 2-heterylthiomethyl-and 2-halomethyl-substituted penicillanates and an ester of 3-chloro-3-methyl-7-chlorocepham-4-carboxylic acid. Also, the desulfurization of 6-chloropenicillanate by Raney nickel has been accomplished. For the substances that have been synthesized, a direct relationship has been established between the intensity of their cytotoxic actionin vitro with respect to tumor cells and the influence of these compounds on the intracellular generation of nitric oxide radicals.Latvian Institute of Organic Synthesis, Riga LV-1006, Translated from Khimiya Geterosiklicheskikh Soedinenii, No. 11, pp. 1494–1503, November, 1998.     

Possibility of separating spent nuclear fuel components by a plasma method in azimuthal magnetic and radial electric fields

We consider the method of plasma separation of spent nuclear fuel in a system with an azimuthal magnetic field and the electric potential produced by electrodes located in a magnetized plasma. The results of calculation of trajectories of ions simulating uranium and the first peak of its fission products in the oneparticle approximation are described. The effect of the initial position and the initial velocity of ions on their trajectories is analyzed. The conditions ensuring the spatial separation of ions in the groups of masses admissible for practical realization are specified; it is shown that currents on the order of 100 kA through the central conductor and electrostatic potentials on the order of 1 kV are required for this purpose.     

Separation of 4C-Substituted Pyrrolidin-2-One Derivatives on Amylose-Based Chiral Stationary Phases

Chromatographia - Our previous studies concerning the enantioseparation of 4C-substituted pyrrolidin-2-one derivatives on coated polysaccharide-based chiral stationary phases have shown that...     

Study of the feasibility of distributed cathodic arc as a plasma source for development of the technology for plasma separation of SNF and radioactive wastes

One of the key problems in the development of plasma separation technology is designing a plasma source which uses condensed spent nuclear fuel (SNF) or nuclear wastes as a raw material. This paper covers the experimental study of the evaporation and ionization of model materials (gadolinium, niobium oxide, and titanium oxide). For these purposes, a vacuum arc with a heated cathode on the studied material was initiated and its parameters in different regimes were studied. During the experiment, the cathode temperature, arc current, arc voltage, and plasma radiation spectra were measured, and also probe measurements were carried out. It was found that the increase in the cathode heating power leads to the decrease in the arc voltage (to 3 V). This fact makes it possible to reduce the electron energy and achieve singly ionized plasma with a high degree of ionization to fulfill one of the requirements for plasma separation of SNF. This finding is supported by the analysis of the plasma radiation spectrum and the results of the probe diagnostics.     

Spin resonance spectroscopy of grown-in defects in Ga(In)NP alloys

We employ the optically detected magnetic resonance (ODMR) technique to study and identify important grown-in defects in Ga(In)NP grown by molecular-beam epitaxy (MBE). Several types of defects were revealed from ODMR studies. The dominant defects were found to be related to Ga interstitials, evident form their characteristic hyperfine interaction arising from the spin interaction between the electron and the Ga nucleus. Some other as yet unidentified intrinsic defects were also found to be commonly present in the alloys. The effects of growth conditions (ion bombardment, N₂ gas flow, etc.) and post-growth rapid thermal annealing on the formation of these defects were studied in detail, shedding light on the formation mechanism of defects.     

CO<Stack><Subscript>2</Subscript><Superscript>−</Superscript></Stack> radicals in synthetic hydroxyapatite

Powders of the B-type synthetic apatite exposed to gamma or ultraviolet irradiation were investigated using EPR spectroscopy. It was shown that ultraviolet irradiation leads to the appearance of the EPR spectrum near g = 2, which is similar to the spectrum observed upon gamma irradiation. The decomposition of the EPR spectra into components and the simulation of the shape of the experimental EPR signals revealed that these signals are associated primarily with two types of CO ₂ ^? radicals, namely, the axial CO ₂ ^? radicals and the orthorhombic CO ₂ ^? radicals. The differences in the shapes of the EPR spectra of the samples exposed to gamma and ultraviolet irradiation were explained by different ratios between the axial and orthorhombic CO ₂ ^? radicals. It was established that thermal annealing results in an increase in the relative contribution to the total EPR spectrum. This increase was explained by the transformation of the orthorhombic radicals into the axial radicals.     

Synthesis and stereoisomerism of derivatives of <Emphasis Type="Italic">tert</Emphasis>-butyl 7-alkylideneceph-3-em-4-carboxylate

By condensation of tert-butyl 3-methyl-7-oxoceph-3-em-4-carboxylate and its 3-acetoxymethyl analog with acetylmethylenetriphenylphosphorane and 3-trimethylsilylpropyn-2-ylindenetriphenylphosphorane tert-butyl 7Z-acetylmethylene-3-methylceph-3-em-4-carboxylate and also 7Z-and 7E-isomers of tert-butyl 3-acetoxymethyl-7-(3-trimethylsilylpropyn-2-ylidene)ceph-3-em-4-carboxylates were synthesized. Oxidation of these compounds with 1 equivalent of meta-chloroperbenzoic acid gave their 1R-and 1S-sulfoxides, and oxidation with 2 equivalents gave the corresponding sulfones. According to data from ¹H NMR spectroscopy, the carbonyl of the β-lactam descreens proton H-9 of the alkylidene group in the 7Z-isomers more strongly than in the 7E-isomers, shifting their signals to weaker field. Analogous shifts of the H-6 signal to weaker field was observed in the 1R-sulfoxides in comparison with that for the 1S-sulfoxide. These results were confirmed by X-ray crystallography of tert-butyl 7Z-acetylmethylene-3-methyl-1S-oxoceph-3-em-4-carboxylate and tert-butyl 7Z-acetylmethylene-3-methyl-1,1-dioxoceph-3-em-4-carboxy-late. In memory of Professor A.A. Potekhin __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 618–626, April, 2008.     

Synthesis and cytotoxic properties of derivatives of the tert-butyl ester of 7-alkylidene-3-methyl-3-cepheme-4-carboxylic acid

Sulfones of the tert-butyl esters of 7-arylmethylene-and 7-(2-furyl)methylene-3-methyl-3-cepheme-4-carboxylic acid were obtained by the condensation of the tert-butyl ester of 3-methyl-7-oxo-3-cepheme-4-carboxylic acid with arylmethylene-and 2-furylidenetriphenylphosphoranes and subsequent oxidation of the intermediate products by meta-chloroperbenzoic acid. The combination of the tert-butyl esters of 7E-bromomethylene-and 7,7-dibromomethylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acids with trimethylsilylacetylene under conditions of the Sonogashira reaction gave the tert-butyl esters of 3-methyl-1,1-dioxo-7E-(3-trimethylsilyl-2-propynylidene)-3-cepheme-4-carboxylic acid and 3-methyl-1,1-dioxo-7-[1,5-bis(trimethylsilyl)-1,4-pentadiyn-3-ylidene]-3-cepheme-4-carboxylic acid. The Vilsmeier reagent was used to incorporate the dimethylaminomethylene group at C-2 of the 7Z-and 7E-isomers of the tert-butyl ester of 7-(4-chlorophenyl)methylene-3-methyl-1,1-dioxo-3-cepheme-4-carboxylic acid. The cytotoxic properties of the derivatives of the tert-butyl ester of 7-alkylidene-3-methyl-3-cepheme-4-carboxylic acid in regard to cancer and normal cells in vitro depends on the structure and 7Z-or 7E-isomerism of the substituent in the 7-alkylidene group as well as the presence of a dimethylaminomethylene group at C-2 of the 3-cepheme system.     

Tetrazoles with oxygen-, sulfur-, and selenium-containing substituents

The data on the synthesis, properties, reactions, and practical application of tetrazoles with oxygen-, sulfur-, and selenium-containing substituents are systematized. Comparative analysis of structure and reactivity was carried out for the compounds under consideration.     

Effect of pre-annealing on NO32- centers in synthetic hydroxyapatite

Effect of pre-annealing of synthetic hydroxyapatite (HAP) on properties of γ- and UV- induced NO₃^2- centers was studied by electron paramagnetic resonance (EPR). Nitrate-containing hydroxyapatite powders ((N)HAP)) and the powders with an admixture of carbonate and nitrate ions ((C,N)HAP) were annealed in the temperature range T_ann = 20 °C ? 600 °C before irradiation. It was found that pre-annealing of (N)HAP samples changes the parameters of NO₃^2- centers while no changes took place in (C,N)HAP. Moreover, at the pre-annealing temperatures T_ann > 200 °C two new NO₃^2- centers were observed in (N)HAP samples; they are characterized by larger value of A_⊥ (3.67 and 4.41 mT) as compared to the known centers. It was also found that the dependence of NO₃^2- centers amount on T_ann is non-monotonous in both types of samples. Presumably this is caused by the escape of water molecules from HAP during the annealing and essential modification of the defect subsystem of HAP.