Human Rad51 protein (HsRad51)-promoted DNA strand exchange, a crucial step in homologous recombination, is regulated by proteins and calcium ions. Both the activator protein Swi5/Sfr1 and Ca2+ ions stimulate different reaction steps and induce perpendicular DNA base alignment in the presynaptic complex. To investigate the role of base orientation in the strand exchange reaction, we examined the Ca2+ concentration dependence of strand exchange activities and structural changes in the presynaptic complex. Our results show that optimal D-loop formation (strand exchange with closed circular DNA) required Ca2+ concentrations greater than 5 mM, whereas 1 mM Ca2+ was sufficient for strand exchange between two oligonucleotides. Structural changes indicated by increased fluorescence intensity of poly(dεA) (a poly(dA) analog) reached a plateau at 1 mM Ca2+. Ca2+ > 2 mM was required for saturation of linear dichroism signal intensity at 260 nm, associated with rigid perpendicular DNA base orientation, suggesting a correlation with the stimulation of D-loop formation. Therefore, Ca2+ exerts two different effects. Thermal stability measurements suggest that HsRad51 binds two Ca2+ ions with KD values of 0.2 and 2.5 mM, implying that one step is stimulated by one Ca2+ bond and the other by two Ca2+ bonds. Our results indicate parallels between the Mg2+ activation of RecA and the Ca2+ activation of HsRad51.

Bridged 1,2,4,5-tetraoxanes were prepared using available acidic ion exchange resin with high yields despite the possibility of peroxide decomposition under heterogeneous conditions. The bridged tetraoxanes demonstrated high cytotoxicity against HeLa cancer cellsin vitro, which in some cases was higher than that of cisplatin, artesunate, and dihydroartemisinin.

Synthetic ozonides and tetraoxanes were shown to have high cytotoxicity in vitro when tested on androgen-independent prostate cancer cell lines DU145 and PC3, which is in some cases was higher than that of doxorubicin, cisplatin, etoposide, artemisinin, and artesunate. Activity of ozonide stereoisomers differs from each other. This difference in activity and absence of correlation between activity of stereoisomers and their oxidative properties allow us to suggest existence of a quite specific mechanism of cytotoxicity of these endoperoxides different from a traditional mechanism based mainly on oxidative properties of peroxides.

Pulmonate gastropod mollusks of the genus Helix are being used by human as food more than 10,000 years and they are quite important in the diet of many European countries.We investigated lipid composition of wild land snails sampled in France, Germany, Luxemburg,Norway, Switzerland, Sweden, and East Mediterranean inhabitants.Plasmalogens, glyceryl ethers, and diacyl phospholipid forms as well as their fatty aldehydes, alkyl ether glycerides, and fatty acid derivatives were studied.PE of snails, containing aldehydes C16 (variations from 17 to 40%), C18 (11-36%), C9-18:1 (22-31%), C11-20:1 (1-3%), and several minor aldehydes, were detected.The major saturated 1-O-alkyl glycerol ethers were C16:0 and C18:0.Eicosatetraenoic (ETA, 34%), α-linolenicacid (ALA, 14%), and eicosapentaenoic acid (EPA, 7%) in PE (all forms) were dominating fatty acids.ETA (49%), EPA (13%), ALA (7%), and docosahexaenoic (DHA, 6%) were major fatty acids in PS (all forms).In PC (all forms), major fatty acids were found oleic (20%), palmitic (15%), ETA (14%), and linoleic (10%).In neutral plasmalogens, the predominant fatty acids were palmitic acid (29%), oleic acid (13%), ALA (8%), and ETA (7.8%).Predominant fatty acids in neutral plasmalogens were found to be 16:0 (29%), C18:0 (13%), ALA (8%), and ETA (7.8%).Distribution of plasmalogens, alkyl glyceryl ethers, and their fatty aldehydes and fatty alcohols in gastropod species and other mollusks is also discussed.

Nitroxyl radicals are widely used in chemistry, materials sciences, and biology. Imide-N-oxyl radicals are subclass of unique nitroxyl radicals that proved to be useful catalysts and mediators of selective oxidation and CH-functionalization. An efficient metal-free method was developed for the generation of imide-N-oxyl radicals from N-hydroxyimides at room temperature by the reaction with (diacetoxyiodo)benzene. The method allows for the production of high concentrations of free radicals and provides high resolution of their EPR spectra exhibiting the superhyperfine structure from benzene ring protons distant from the radical center. An analysis of the spectra shows that, regardless of the electronic effects of the substituents in the benzene ring, the superhyperfine coupling constant of an unpaired electron with the distant protons at positions 4 and 5 of the aromatic system is substantially greater than that with the protons at positions 3 and 6 that are closer to the N-oxyl radical center. This is indicative of an unusual character of the spin density distribution of the unpaired electron in substituted phthalimide-N-oxyl radicals. Understanding of the nature of the electron density distribution in imide-N-oxyl radicals may be useful for the development of commercial mediators of oxidation based on N-hydroxyimides.

A one-pot procedure was developed for the assembly of bicyclic compounds containing 1,2-dioxolane and tetrahydrofuran rings based on the reaction of 2-allyl-1,3-diketones with the I2/H2O2 system. A fivefold molar excess of H2O2 and a twofold excess of I2 are required for the selective formation of tetrahydrofurodioxoles. The synthesis of these structurally complex molecules is unusual in that it does not produce the expected bridged tetraoxanes, products of the addition of several H2O2 molecules to a carbonyl group, or the products of double bond iodoperoxidation.

Dmitri O Levitsky1, Tatyana A Gloriozova2, Vladimir V Poroikov2, Valery M Dembitsky3 1CNRS UMR 6204, Biotechnologie, Biocatalyse et Biorégulation, Faculté des Sciences et des Techniques, Université de Nantes Nantes, 44322 Nantes Cedex 03, France. 2Institute of Biomedical Chemistry, Moscow 119121, Russia. 3Institute for Drug Discovery, P.O. Box 45289, Jerusalem 91451, Israel. Corresponding Author: Valery M. Dembitsky, Institute for Drug Discovery, 8 Ha-Marpe Str, P.O. Box 45289, Jerusalem 91451, Israel, Tel: +972-526877444; Email: iddrdo@gmx.com

A new organocatalytic approach for the synthesis of peroxides based on СН activation of a sp3-hybridized carbon atom is reported. Peroxides were prepared in 31–89% yield by the reaction of malonates, β-ketoesters, and cyanoacetic esters with a Bu4NI/tert-butyl hydroperoxide system. The formation of the expected hydroxylation products was not observed. In the discovered reaction, tert-butyl hydroperoxide plays a dual role by acting as the oxidant and the O-reagent for the C–O coupling. The synthesis can be scaled up to generate gram quantities of the target products.

Upon emergence of modern anticancer therapy, medical community is divided into two opposite camps, one of them claiming absolute necessity of using isolated or synthesized chemical compounds for efficient patient treatment and another one advocating alternative cancer therapies, in particular those based on natural sources, including extracts from plants. It seems, in reality, that the two camps are reconcilable: while natural sources, plant extracts or juices play both curative and protective role, drugs represent the ultimate possibility to inhibit or reverse tumor development. In this paper we tried to analyze anti-breast cancer potencies of quite a few extracts from different plant sources and to compare their anti-proliferative efficiency of crude extracts with actions of their purified ingredients.

A facile method was developed for the preparation of microsized cerium chloride, which is an efficient catalyst in the Michael addition reaction.

The reaction of β,δ-triketones with an ethereal solution of H2O2 catalyzed by heteropoly acids in the presence of a polar aprotic co-solvent proceeds via three pathways to form three classes of peroxides: tricyclic monoperoxides, bridged tetraoxanes, and a pair of stereoisomeric ozonides. The reaction is unusual in that produces bridged tetraoxanes and ozonides with one of the three carbonyl groups remaining intact. In the synthesis of bridged tetraoxanes, the peroxide ring is formed by the reaction of hydrogen peroxide with two carbonyl groups at the β positions. The synthesis of ozonides from ketones and hydrogen peroxide is a unique process in which the ozonide ring is formed with the participation of two carbonyl groups at the δ positions. Rearrangements of ozonides were found for the first time after more than one century of their active investigation. Ozonides are interconverted with each other and rearranged into tricyclic monoperoxides, whereas ozonides and tricyclic monoperoxides are transformed into bridged tetraoxanes. The individual reaction products were isolated by column chromatography and characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. One representative of each class of peroxides was characterized by X-ray diffraction.

Phosphomolybdic acid (PMA) and phosphotungstic acid (PTA) efficiently catalyze the addition of H2O2 to β-diketones to form bridged 1,2,4,5-tetraoxanes. These reactions are not accompanied by the formation of monocyclic peroxides containing hydroxy and hydroperoxide groups or polymeric peroxides. The use of these catalysts made it possible to obtain bridged tetraoxanes from easily oxidizable benzoylacetone derivatives and α-unsubstituted β-diketones. The syntheses are scaled up to ten grams. The resulting peroxides can be easily isolated from the reaction mixture by column chromatography. The yield of tetraoxanes depends on the structure of β-diketone and varies from 12 to 83%. NMR monitoring of two bridged 1,2,4,5-tetraoxanes synthesis was carried out.

Sodium-calcium exchange across plasma membrane is regulated by intracellular calcium ions. The sodium-calcium exchanger (NCX1) is activated by successive saturation of numerous Ca2+-binding sites located in the intracellular loop of the protein. The progressive saturation of the binding domain CBD12 by Ca2+ results in a series of conformational changes of CBD12 as well as of entire NCX1 molecule. Like other soluble and membrane Ca2+-binding proteins, NCX1 can also be regulated by Mg2+ that antagonises Ca2+ at the level of divalent cation-binding sites. This chapter summarises data on Mg2+ impacts in the cells. Regulatory action of Mg2+ on intracellular Ca2+-dependent processes can be achieved due to changes of its cytoplasmic level, which take place in the range of [Mg2+]i from 0.5 to 3 mM. Under normal conditions, these changes are ensured by activation of plasmalemmal Mg2+ transport systems and by variations in ATP level in cytoplasm. In heart and in brain, some pathological conditions, such as hypoxia, ischemia and ischemia followed by reperfusion, are associated with an important increase in intracellular Ca2+. The tissue damage due to Ca2+ overload may be prevented by Mg2+. The protective actions of Mg2+ can be achieved due to its ability to compete with Ca2+ for the binding sites in a number of proteins responsible for the rise in intracellular free Ca2+, including NCX1, in case when the reverse mode of Na+/Ca2+ exchange becomes predominant. Saturation of CBD12 by Mg2+ results in important changes of NCX1 conformation. Modulating actions of Mg2+ on the conformation of NCX1 were detected at a narrow range of Mg2+ concentration, from 0.5 to 1 mM. These data support an idea that variations of intracellular Mg2+ could modify transmembrane Ca2+ movements ensured by NCX1.

Endogenous low molecular weight redox active compounds (RACs) comprise antioxidants, pro-oxidants, transition metal cations and metal chelators. Traditional electrochemical methods of measuring RACs are limited to aqueous solutions, thus providing information of only hydrophilic RAC pools. In a large number of diseases associated with oxidative stress and/or with metal toxicity, redox states of hydrophilic as well as hydrophobic compartments are modified, and therefore development of methods for their detection is both necessary and important. The pools of lipid soluble RACs in reduced and oxidized forms in n-hexane extracts obtained from blood plasma, erythrocytes and whole blood of healthy donors were determined by spectrophotometric detection of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals, which stoichiometrically interacts with hydrogen donors in non polar solutions. Measurements of RACs in extracts before and after treatment with NaBH4 provided information about the levels of both reduced and oxidized RACs. Vitamin E was also determined using a fluorescence method. The results have shown that vitamin E is the major RAC in blood plasma lipids but not in blood cell lipids, where other phenols and quinones appear to predominate.

A comparative study on the free amino acids of 15 wild edible mushroom species belonging to the genus Boletus (phylum Basidiomycota) was developed. The major amino acids in the fruit bodies were arginine, alanine, glutamine, and glutamic acid. The most abundant fatty acids were oleic (9-18:1), linoleic acid (9,1218:2), and palmitic acid (16:0), but a great variation of the ester composition from one to another one was found. Chemical constituents were characterized by GC-MS, and other chemical methods.

Biodiversity of secondary lichen metabolites by the epiphytic and lithophilic lichens of the genus Collema is reported. The most abundant fatty acids were α-linolenic acid (18:3n-3), oleic acid (18:1n-9), and palmitic acid (16:0), but a great variation of the ester composition from one to another was found. A comparison of neutral lipids, glycolipids, polar lipids and fatty acid composition of four species was done. DGTS, DGTA, PC, and PI were found as major components among polar lipids. Chemical constituents were characterized by GC-MS, HPLC, HR-TLC, and other chemical methods. Biological activity of isolated compounds from Collema species is also discusses. Several indole alkaloids and other nitrogen-containing metabolites have been isolated

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