Jon Songstad

Tetradecylthioacetic acid and tetradecylselenoacetic acid inhibit lipid peroxidation and interact with superoxide radical.

Reactive oxygen species are thought to induce cellular damage and to play a pathological role in several human diseases. Tetradecylthioacetic acid (TTA) was previously reported to prevent the oxidative modification of low-density lipoprotein (LDL) particles and to act as an antioxidant. In this study we present a new fatty acid analogue, namely tetradecylselenoacetic acid (TSA), in which the sulfur atom of TTA is replaced by a selenium atom. TSA was more potent than TTA in increasing the lag time before the onset of LDL oxidation and this effect was dose dependent. TTA and TSA were shown to reduce the iron-ascorbate-induced microsomal lipid peroxidation, TSA being more efficient than TTA. TTA and TSA, in the presence of iron, interacted with the superoxide radical as assessed by direct and indirect testing methods. TSA like TTA failed to scavenge 1.1-diphenyl-2-picrylhydrazyl radicals. TSA bound copper ions as shown by the wavelength spectra measurement. These results suggest that TTA and TSA exert their antioxidant capacity by interaction with copper or iron ions in radical scavenging, TSA being more potent than TTA. Nevertheless, a chelating effect resulting in chemically inactive metal ions cannot be excluded.

Reaction of Selenium with Bromine (Se:Br = 1:1) in Acetonitrile in the Presence of Tetramethylammonium Bromide: Synthesis and Crystal Structure of [(CH3)4N]2[Se16Br18], the Salt of a Unique Bromoselenate(I) Anion

Red crystals of [(CH3)4N]2[Se16Br18] (1) were isolated when selenium and bromine were allowed to react in acetonitrile solution in the presence of tetramethylammonium bromide. The salt 1 crystallizes in the monoclinic space group P 21/n with the cell dimensions a = 12.1876(4) A, b = 18.9670(4) A, c = 12.2390(4) A, s = 91.908(2) ° (123 K). In the solid state structure the [Se16Br18]2— anion consists of two [Br(Se2Br2)4]— subunits which are related by an inversion centre and connected by 4 weak Se—Br bonds (3.2588(9) A and 3.3887(9) A, respectively). Each monoanionic subunit may be regarded as built up of 4 Se2Br2 molecules, coordinated to a central bromide ion at distances of 3.0731(9)—3.1061(9) A. The structure of the [Se16Br18]2— dianion can also be formally derived from the known [Se4Br6]2— dianion which uses each of its two bridging bromo ligands for coordination of 3 additional Se2Br2 molecules. Umsetzung von Selen mit Brom (Se:Br = 1:1) in Acetonitril in Gegenwart von Tetramethylammonium-bromid: Synthese und Kristallstruktur von [(CH3)4N]2[Se16Br18], dem Salz eines neuartigen Bromoselenat(I)-Anions Rote Kristalle von [(CH3)4N]2[Se16Br18] (1) liesen sich isolieren, wenn Selen und Brom in Acetonitril-Losung in Gegenwart von Tetramethylammonium-bromid zur Reaktion gebracht wurden. Das Salz 1 kristallisiert in der monoklinen Raumgruppe P 21/n mit den Zellkonstanten a = 12.1876(4) A, b = 18.9670(4) A, c = 12.2390(4) A, s = 91.908(2)° (123 K). In der Festkorperstruktur besteht das Anion [Se16Br18]2— aus zwei [Br(Se2Br2)4]— Untereinheiten, die uber ein Inversionszentrum in Zusammenhang stehen und uber 4 schwache Se—Br Bindungen (3.2588(9) bzw. 3.3887(9) A) miteinander verknupft sind. Jede der beiden monoanionischen Untereinheiten lasst sich aus 4 Se2Br2-Molekulen aufbauen, die (mit Abstanden von 3.0731(9) bis 3.1061(9) A) an ein zentrales Bromid-Ion koordiniert sind. Die Struktur des Dianions [Se16Br18]2— kann formal auch aus dem bekannten Dianion [Se4Br6]2— abgeleitet werden, wenn an die beiden bruckenstandigen Bromo-Liganden zusatzlich jeweils 3 Molekule Se2Br2 angelagert werden.

Dielectric properties of solutions of tetra-iso-pentylammonium nitrate in dioxane-water mixtures

Dielectric properties of solutions of tetra-iso-pentylammonium nitrate, i-Pen4NNO3. in various dioxane-water mixtures have been studied using dielectric time domain spectroscopy (TDS). The static permittivity of the solutions ɛs increases for low concentrations of solute but levels off to asymptotic values at higher concentrations. The limiting slopedɛsdc, and the asymptotic value depend on the static permittivity of the solvent mixture. The relaxation time due to the solute varies with solute concentration and depends on the solvent mixture. In the solvent mixtures of lowest permittivity the plots of relaxation time vs. concentration go through a maximum, while in the mixtures of highest permittivity the relaxation time initially decreases and then levels off to an asymptotic value. The concentration dependence of the dielectric parameters is discussed in relation to ion association.

Thia fatty acids with the sulfur atom in even or odd positions have opposite effects on fatty acid catabolism.

As tools for mechanistic studies on lipid metabolism, with the long-term goal of developing a drug for the treatment of lipid disorders, thia FA with the sulfur atom inserted at positions 3–9 from the carboxyl group were fed to male Wistar rats for 1 wk to determine their impact on key parameters in lipid metabolism and hepatic levels of thia FA metabolites. Thia FA with the sulfur atom in even positions decreased hepatic and cardiac mitochondrial β-oxidation and profoundly increased hepatic and cardiac TAG levels. The plasma TAG level was unchanged and the hepatic acyl-CoA oxidase activity increased. In contrast, thia FA with the sulfur atom in odd positions, especially 3-thia FA, tended to increase hepatic and cardiac FA oxidation and acyl-CoA oxidase and carnitine palmitoyltransferase-II activities, and decreased the plasma TAG levels. The effects seem to be related to differences in the catabolic rate of the thia FA. Differences between the two groups of acids were also observed with respect to the regulation of genes involved in FA transport and catabolism. Feeding experiments with 3- and 4-thia FA in combination indicated that the 4-thia FA partly attenuated the effects of the 3-thia FA on mitochondrial FA oxidation and the hepatic TAG level. In summary, the position of the sulfur atom in the alkyl chain, especially whether it is placed in the even or odd position, is crucial for the biological effect of the thia FA.

Enhanced hepatic fatty acid oxidation and upregulated carnitine palmitoyltransferase II gene expression by methyl 3-thiaoctadeca-6,9,12,15-tetraenoate in rats

This study reports the effects of a novel polyunsaturated 3-thia fatty acid, methyl 3-thiaoctadeca-6,9,12,15-tetraenoate on serum lipids and key enzymes in hepatic fatty acid metabolism compared to a saturated 3-thia fatty acid, tetradecylthioacetic acid. Palmitic acid treated rats served as controls. Fatty acids were administered by gavage in daily doses of 150 mg/kg body weight for 10 days. The aim of the present study was: (a) To investigate the effect of a polyunsaturated 3-thia fatty acid ester, methyl 3-thiaoctadeca-6,9,12,15-tetraenoate on plasma lipids in normolipidemic rats: (b) to verify whether the lipid-lowering effect could be consistent with enhanced fatty acid oxidation: and (c) to study whether decreased activity of esterifying enzymes and diversion to phospholipid synthesis is a concerted mechanism in limiting the availability of free fatty acid as a substrate for hepatic triglyceride formation. Repeated administration of the polyunsaturated 3-thia fatty acid ester for 10 days resulted in a reduction of plasma triglycerides (40%), cholesterol (33%) and phospholipids (20%) compared to controls. Administration of polyunsaturated and saturated 3-thia fatty acids (daily doses of 150 mg/kg body weight) reduced levels of lipids to a similar extent and followed about the same time-course. Both mitochondrial and peroxisomal fatty acid oxidation increased (1.4-fold- and 4.2-fold, respectively) and significantly increased activities of carnitine palmitoyltransferase (CPT) (1.6-fold), 2,4-dienoyl-CoA reductase (1.2-fold) and fatty acyl-CoA oxidase (3.0-fold) were observed in polyunsaturated 3-thia fatty acid treated animals. This was accompanied by increased CPT-II mRNA (1.7-fold). 2,4-dienoyl-CoA reductase mRNA (2.9-fold) and fatty acyl-CoA oxidase mRNA (1.7-fold). Compared to controls, the hepatic triglyceride biosynthesis was retarded as indicated by a decrease in liver triglyceride content (40%). The activities of glycerophosphate acyltransferase, acyl-CoA: 1,2-diacylglycerol acyltransferase and CTP:phosphocholine cytidylyltransferase were increased. The cholesterol lowering effect was accompanied by a reduction in HMG-CoA reductase activity (80%) and acyl-CoA:cholesterol acyltransferase activity (33%). In hepatocytes treated with methyl 3-thiaoctadeca-6,9,12,15-tetraenoate, fatty acid oxidation was increased 1.8-fold compared to controls. The results suggest that treatment with methyl 3-thiaoctadeca-6,9,12,15-tetraenoate reduces plasma triglycerides by a decrease in the availability of fatty acid substrate for triglyceride biosynthesis via enhanced fatty acid oxidation, most likely attributed to the mitochondrial fatty acid oxidation. It is hypothesized that decreased phosphatidate phosphohydrolase activity may be an additive mechanism which contribute whereby 3-thia fatty acids reduce triglyceride formation in the liver. The cholesterol-lowering effect of the polyunsaturated 3-thia fatty acid ester may be due to changes in cholesterol/cholesterol ester synthesis as 60% of this acid was observed in the hepatic cholesterol ester fraction.

3,3'-Selenobis(propionic acid)

In contrast to Se[CH(2)C(O)OH](2) versus S[CH(2)C(O)OH](2), the title compound, Se[CH(2)CH(2)C(O)OH](2) or C(6)H(10)O(4)Se, is structurally quite similar to its sulfur analogue. The molecule has twofold symmetry. The C-Se-C bond angle is 96.48 (8) degrees and the Se-C bond lengths are 1.9610 (14) A. The shortest Se.O intermolecular distance is 3.5410 (11) A. The O.O distances in the carboxylic acid dimers are 2.684 (2) A. The temperature dependence of the IR spectrum suggests tautomerism in the solid state.

Spectral studies of tetrabutylammonium bis(thiocyanate-S)phenylpyridinate(C,N)platinate(II)

The spectral and luminescent properties of tetrabutylammonium bis(thiocyanate-S)phenylpyridinate(C, N)platinate(II) were studied at 77 and 298 K in the polycrystalline state, frozen solutions, and polystyrene and polymethyl methacrylate films. The nature and properties of the electronically excited state of the complex responsible for its luminescence are determined.

Ditetradecyl selenide, (C14H29)2Se, a new chemical shift reference compound for 77Se NMR

Ditetradecyl selenide, (C14H29)2Se, is suggested as an alternative to Me2Se as a reference compound for 77Se NMR in organic solvents. This selenide, a crystalline, non‐odorous and stable compound, is readily prepared and purified and is sufficiently soluble in most of the usual organic solvents at room temperature to give a satisfactory 77Se signal; in methanol, acetonitrile and dimethyl sulfoxide temperatures above ∼310 K are required. The chemical shifts, +162.3 ppm in CDCl3 at 298 K relative to a 60% solution of Me2Se in CDCl3, defined as 0.0 ppm, and +167.2 ppm relative to a 0.25 M solution of Me2Se in CDCl3, is independent of the concentration in the 0.01–0.40 M range. The shift in CDCl3 increases fairly linearly with temperature in the 270–345 K range with a slope of ∼0.075 ppm K−1. The shift appears to be less dependent upon the solvent than the shift of Me2Se. Copyright

Preparation and NMR studies of 3-selenaheptadecanoic and 4-selenaoctadecanoic acid, RSe(CH2)nC(O)OH (R = C14H29, n = 1 and 2), and their methyl esters

The synthesis of the title compounds and their precursor, ditetradecyl diselenide, R2Se2, in high yield and of high purity is described. A 600 MHz 1H NMR study at 298 K in CDCl3 and CCl4 has revealed that 4-selenaoctadecanoic acid displays a singlet for the 2- and 3-H2 protons integrating for four protons, while the corresponding sulfur compound shows the expected doublet of triplets. Only in C6D6, and partly in (CD3)2SO, are the signals due to these protons sufficiently separated to give two triplets. No obvious relationship between the form of the spectra and any of the usual solvent parameters could be found. The particular form of the 1H NMR spectrum in CDCl3 and CCl4 was found to be independent of the concentration, i.e. the monomer∶dimer ratio. A temperature study has revealed that while the signal due to the 3-H2 protons is essentially independent of the temperature, the 2-H2 proton signal is shifted downfield with decreasing temperature, causing the close-lying signals to be indistinguishable in the 290–310 K range. NMR spectra of the carboxylic OH group and IR spectra of the carbonyl group of dilute solutions of 3-selena- and 3-thiaheptadecanoic acids in CCl4 suggest that the monomers of these acids exist predominantly as 4-membered cyclic species with Se(S)⋯OC or Se(S)⋯O(H) intramolecular interactions.

4-(Trifluoromethyl)benzonitrile

4-(Trifluoromethyl)benzonitrile, C(8)H(4)F(3)N, at 123K contains molecules linked together through one C-H...F bond and two C-H...N hydrogen bonds into sheets that are further crosslinked to form a dense two-dimensional network without pi...pi ring interactions. The aromatic ring is slightly deformed due to the two para-related electronegative groups.