Biomedical subjects

Eric Block

Publications and source records attributed to Eric Block.

17 recordsLinked to original sources

PubMed2006

Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds.

Inorganic arsenic (arsenite and arsenate) in drinking water has been associated with skin cancers and increased incidence of cardiovascular diseases. Additionally, studies have demonstrated the pro-angiogenic effect of arsenite and its potential promotion of tumor angiogenesis and tumor progression. Furthermore, recent reports demonstrated reversal of skin co-carcinogenesis by an organoselenium compound. The present study was undertaken to determine the effect and mechanism on angiogenesis of arsenite at low level and its potential reversal by various selenium-derived compounds. The pro-angiogenesis effects and mechanisms of sodium arsenite were determined using the chick chorioallantoic membrane (CAM) model over 3 days and compared with standard pro-angiogenesis factors, such as basic fibroblast growth factor (b-FGF). Additionally, the potential effect of various selenium-derived compounds--such as dimethyl selenone, diphenyl selenone, sodium selenite or Se-methyl selenocysteine--in reversing the pro-angiogenesis effect of arsenite or b-FGF was also determined in the CAM model. The pro-angiogenesis effect of arsenite or b-FGF was significantly (P < 0.01) blocked by dimethyl selenone, diphenyl selenone, sodium selenite or Se-methyl selenocysteine. The pro-angiogenesis effect of either sodium arsenite at 33 nM or b-FGF was blocked (P < 0.01) by the extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation inhibitor, PD 98059. Additionally, the pro-angiogenic effect of arsenic or b-FGF was blocked as well (P < 0.01) by the alphavbeta3 antagonist, XT199. These data suggest that the pro-angiogenesis effect of arsenic is initiated at the plasma membrane integrin alphavbeta3, involves activation of the ERK1/2 pathway and is effectively reversed by various selenium-derived compounds.

Angiogenesis Inducing Agents↗

PubMed2006

Synthesis, structure, and chemistry of new, mixed group 14 and 16 heterocycles: nucleophile-induced ring contraction of mesocyclic dications.

More than 40 new 4- to 12-membered ring heterocycles containing various combinations of Group 14 and 16 elements Si, Sn, S, Se, and Te have been synthesized and fully characterized. Synthesis of these small-ring as well as medium-ring (mesocyclic) heterocycles from alpha,omega-dihalides is facilitated by the presence of gem-dialkylsilyl and gem-dialkylstannyl groups in the precursors. Conformations of several of the new ring systems in the solid state have been determined by X-ray crystal structure analysis. Oxidation of mixed S(Se, Te)/Si eight-membered ring mesocycles with NOPF6 or Br2 gives dications or a bicyclic dibromide, respectively, which can be characterized by NMR methods. On treatment with nucleophiles, mesocyclic dications, or the corresponding radical cations undergo ring contraction, giving five- or six-membered ring heterocycles. Photolysis of a S/Se four-membered ring heterocycle gives selenoformaldehyde, trapped in 80% yield with 2,3-dimethyl-1,3-butadiene.

Journal Article↗

PubMed2006

The Si-Si effect on ionization of beta-disilanyl sulfides and selenides.

The ionization energies of conformationally constrained, newly synthesized beta-disilanyl sulfides and selenides were determined by photoelectron spectroscopy. These ionization energies reflect substantial (0.53-0.75 eV) orbital destabilizations. The basis for these destabilizations was investigated by theoretical calculations, which reveal geometry-dependent interaction between sulfur or selenium lone pair orbitals and sigma-orbitals, especially Si-Si sigma-orbitals. These results presage facile redox chemistry for these compounds and significantly extend the concept of sigma-stabilization of electron-deficient centers.

Journal Article↗

PubMed2005

Dimethyl selenoxide.

The title molecule, C2H6OSe, has a trigonal-pyramidal structure analogous to that of its sulfur analog, dimethyl sulfoxide (DMSO). The Se-O distance in dimethyl selenoxide (DMSeO) is 1.6756 (16) A [versus S-O of 1.531 (5) A in DMSO], consistent with a highly polar bond. In the solid state, the molecules of DMSeO are linked into centrosymmetric dimers formed by two C-H...O hydrogen bonds. These dimers further aggregate into a ladder-like supramolecular network via two additional intermolecular C-H...O interactions. As a result, each O atom of DMSeO acts as an acceptor of three hydrogen bonds.

Dimethyl Sulfoxide↗

PubMed2005

Encoding social signals in the mouse main olfactory bulb.

Mammalian urine releases complex mixtures of volatile compounds that are used in reproduction, territoriality and conspecific recognition. To understand how such complex mixtures are represented in the main olfactory bulb, we analysed the electrophysiological responses of individual mitral cells to volatile compounds in mouse urine. In both males and females, urine volatile compounds evoke robust responses in a small subset of mitral cells. Fractionation of the volatile compounds using gas chromatography showed that out of the hundreds of compounds present, mitral cells are activated by single compounds. One cohort of mitral cells responded exclusively to male urine; these neurons were activated by (methylthio)methanethiol, a potent, previously unknown semiochemical present only in male urine. When added to urine, synthetic (methylthio)methanethiol significantly enhances urine attractiveness to female mice. We conclude that mitral cells represent natural odorant stimuli by acting as selective feature detectors, and that their activation is largely independent of the presence of other components in the olfactory stimulus.

Animals↗

PubMed2005

Spirocyclic sulfur and selenium ligands as molecular rigid rods in coordination of transition metal centers.

A set of analogous chalcogen-containing spirocycles, 2,6-dithiaspiro[3.3]heptane, 2,6-diselenaspiro[3.3]heptane, and 2-thia-6-selenaspiro[3.3]heptane [E(2)C(5)H(8), E = S (1), Se (2), and S/Se (3)], has been prepared and fully characterized by spectroscopic methods and by X-ray diffraction. The structural characterization of 2 was presented by us earlier, while the crystal structures of 1 and 3 are reported here for the first time. Molecules 1-3 are built around the central tetrahedral carbon atom and therefore are nonplanar. The E...E separation ranges from 4.690(1) A in 1 to 4.906(1) A in 2. Molecule 3 has statistically mixed positions of sulfur and selenium atoms in the solid state with all geometric characteristics being intermediate between those of 1 and 2. Compounds 2 and 3 have been tested as molecular rigid rod ligands in coordination reactions with transition metal complexes such as Cu(hfac)(2) (4), cis-Co(hfac)(2).2H(2)O (5), and cis-Ni(hfac)(2).2H(2)O (6) (hfac = hexafluoroacetylacetonate). Several coordination products built of two building blocks, M(hfac)(2) (M = Cu, Co, and Ni) and Se(2)C(5)H(8) (2), have been prepared in crystalline form and structurally characterized. The copper-based product (7) is comprised of the oligomeric units {[Cu(hfac)(2)](3).2mu(2)-Se(2)C(5)H(8)-Se,Se'} built on the axial Cu...Se interactions averaged at 2.909 A. These units are further assembled into 1D polymeric chains via intermolecular Cu...F contacts at 2.829 A. The SSeC(5)H(8) (3) ligand was also used in the reaction with Cu(hfac)(2) to afford an analogue of 7, namely {[Cu(hfac)(2)](3).2mu(2)-SSeC(5)H(8)-S,Se} (8). Complex 8 exhibits statistically mixed positions of the donor sulfur and selenium atoms to give an average axial Cu...S/Se contact at 2.892 A. In contrast to the copper complexes of composition 3:2, the stoichiometries of the isolated cobalt and nickel products are 1:1, [M(hfac)(2).Se(2)C(5)H(8)] (M = Co (9) and Ni (10)). Complexes 9 and 10 exhibit 1D polymer structures having alternating metal units cis-M(hfac)(2) and ligands 2 with intermolecuar M...Se separations of 2.6046(8) and 2.5523(16) A, respectively. In all products 7-10 the initial cis or trans geometry of M(hfac)(2) complexes is preserved and the spiro[3.3]heptane ligands act as bidentate linkers bridging transition metal centers via both donor ends. The magnetic properties of this series of new Cu(II), Co(II), and Ni(II) complexes have been tested by variable-temperature magnetic susceptibility measurements.

Journal Article↗

PubMed2004

Powder diffraction study of a coordination polymer comprised of rigid building blocks: [Rh2(O2CCH3)4.mu2-Se2C5H8-Se,Se']infinity.

The crystal structure of a new hybrid product comprised of two rigid building blocks, namely dirhodium(II) tetraacetate, [Rh(2)(O(2)CCH(3))(4)] (1), and 2,6-diselenaspiro[3.3]heptane, Se(2)C(5)H(8) (2), has been solved ab initio using laboratory source X-ray powder diffraction (XRPD) data. The rigid body refinement approach has been applied to assist in finding an adequate model and to reduce the number of the refined parameters. Complex [Rh(2)(O(2)CCH(3))(4).mu(2)-Se(2)C(5)H(8)-Se,Se'] (3) conforms to the triclinic unit cell with lattice parameters of a = 8.1357(4), b = 8.7736(4), and c = 15.2183(8) A, alpha = 77.417(3), beta = 88.837(3), and gamma = 69.276(4) degrees, V = 989.66(8) A(3), and Z = 2. The centrosymmetric P space group was selected for calculations. The final values of the reduced wR(p), R(p), and chi(2) were calculated at 0.0579, 0.0433, and 5.95, respectively. The structure of 3 is a one-dimensional zigzag polymer built on axial Rh...Se interactions at 2.632(6) A. The 2,6-diselenaspiro[3.3]heptane ligand acts as a bidentate linker bridging dirhodium units via both selenium atoms. The geometrical parameters of individual groups for rigid body refinement have been obtained from X-ray powder data for dirhodium(II) tetraacetate (1) and from single-crystal X-ray diffraction for diselenium molecule 2. The crystal structures of 1 and 2 are reported here for the first time. For 1 indexing based on XRPD data has resulted in the triclinic unit cell P with lattice parameters of a = 8.3392(7), b = 5.2216(5), and c = 7.5264(6) A, alpha = 95.547(10), beta = 78.101(6), and gamma = 104.714(13) degrees, V = 309.51(5) A(3), and Z = 1. The final values were wR(p) = 0.0452, R(p) = 0.0340, and chi(2) = 1.99. The 1D polymeric motif built on axial Rh.O interactions of the centrosymmetric dirhodium units has been confirmed for the solid-state structure of 1. Compound 2,6-diselenaspiro[3.3]heptane (2) conforms to the monoclinic space group P2(1)/c with the unit cell parameters of a = 5.9123(4), b = 19.6400(13), and c = 5.8877(4) A, beta = 108.5500(10) degrees, V = 648.15(8) A(3), and Z = 4.

Copper↗

PubMed2004

Identification and synthesis of a novel selenium-sulfur amino acid found in selenized yeast: Rapid indirect detection NMR methods for characterizing low-level organoselenium compounds in complex matrices.

After proteolytic digestion, aqueous extraction, and derivatization with diethyl pyrocarbonate or ethyl chloroformate, HPLC-inductively coupled plasma (ICP)-MS, GC-atomic emission detection (AED), and GC-MS analysis of high-selenium yeast stored at room temperature for more than 10 years showed selenomethionine as the major Se product along with substantial amounts of selenomethionine selenoxide hydrate and the previously unreported selenoamino acid having a Se-S bond, S-(methylseleno)cysteine. The identity of the latter compound was confirmed by synthesis. The natural product was shown to be different from a synthetic sample of the isomeric compound Se-(methylthio)selenocysteine. Selenium-specific NMR spectroscopic methods were developed to directly analyze the aqueous extracts of the hydrolyzed selenized yeast without derivatization or separation. Selenomethionine and S-(methylseleno)cysteine were identified by 77Se-1H HMQC-TOCSY experiments.

Chromatography, High Pressure Liquid↗

PubMed2004

Aversion of European starlings (Sturnus vulgaris) to garlic oil treated granules: garlic oil as an avian repellent. Garlic oil analysis by nuclear magnetic resonance spectroscopy.

European starlings significantly reduced their consumption of a food mixture that was 50% food-grade garlic oil (GO)-impregnated granules, even after overnight food deprivation, as demonstrated by "one-choice" ("no-choice") tests. Food consumption during 3 h following overnight food deprivation was reduced by 61-65% compared to controls. By testing the same subjects with 25, 10, and 1% mixtures of granules in feed, it was shown that commercial GO granules were repellent to birds in lower concentrations, with more than a 50% decrease in feeding for birds presented with a 10% mixture of commercial GO granules in food and a 17% decrease for the 1% treatment. Products containing GO show considerable promise as inexpensive, environmentally benign, nonlethal bird repellents. In comparing various GO preparations used in this work, nuclear magnetic resonance (NMR) spectroscopic methods prove to be particularly useful for rapid quantitation of major and minor components without requiring fractionation or isolation procedures, which could adversely effect the less stable components.

Allyl Compounds↗

PubMed2004

Chloromethanesulfonylethene and dichloromethanesulfonylethene: new reagents for tandem Diels-Alder/Ramberg-Bäcklund reactions.

[reaction: see text] Chloromethanesulfonylethene (3a) and dichloromethanesulfonylethene (3b) were prepared by oxidation of the adducts of ethylene and ClCH(2)SCl or Cl(2)CHSCl, respectively, followed by NaHCO(3) dehydrochlorination. With dienes, 3a gave Diels-Alder adducts that, with base, underwent Ramberg-Bäcklund reaction, giving products corresponding to the adducts of the dienes and allene. Similarly, 3b gave Diels-Alder adducts that, with base in the presence of the novel chlorine source MeSO(2)CCl(3), cleanly afforded products corresponding to the adducts of the dienes and 1,1-dichloropropa-1,2-diene.

Journal Article↗

PubMed2004

The sulfur chemistry of shiitake mushroom.

Allium herbs, such as Chinese chive, garlic, and onion, share a common sulfur biochemistry that occurs on cell breakage. Sulfoxide precursors are converted enzymatically to sulfenic acid intermediates and thence to a variety of pungent and in some cases noxious sulfur species that probably act to deter herbivores. Very similar biochemistry has been proposed to occur in shiitake mushrooms. Prior to the present work, our understanding of the sulfur biochemistry of these plants and fungi has been derived largely from conventional analysis procedures. We have used in situ sulfur K-edge X-ray absorption spectroscopy in intact and disrupted allium plants and shiitake mushroom. The expected changes in sulfur forms following cell breakage are indeed observed for the alliums, but no significant changes occur for the fungus. Thus, any changes involving the sulfur-containing compounds of shiitake mushroom following cell breakage occur to a far smaller extent than those involving allium plants, presumably reflecting the need in shiitake for action by multiple enzymes, namely a gamma-glutamyl transpeptidase and a C-S lyase. The shiitake C-S lyase occurs in far lower concentrations than the corresponding enzyme in garlic. Furthermore, cleavage of the flavorant precursor by the shiitake C-S lyase is reported to cease before cleavage of the precursor has been completed, presumably due to a product or suicide inhibition mechanism.

Shiitake Mushrooms↗

PubMed2003

The first coordination complexes of selenones: a structural comparison with complexes of sulfones.

Reactivity of the two classes of very weak donors R(2)XO(2) (X = S, R = Me (1) and Ph (2); X = Se, R = Me (3) and Ph (4)) have been studied. Coordination properties of sulfones and selenones in solution and in the gas phase have been compared for the first time using a model bidentate metal complex, [Rh(2)(O(2)CCF(3))(4)]. Two coordination modes, bridging mu(2)-O,O' and terminal eta(1)-O, have been detected. These types of binding were realized in two series of sulfone and selenone metal complexes, polymeric mono-adducts [Rh(2)(O(2)CCF(3))(4).(R(2)XO(2))]( infinity ) (X = S, R = Me (1a); R = Ph (2a); X = Se, R = Ph (4a)) and discrete bis-adducts [Rh(2)(O(2)CCF(3))(4).(R(2)XO(2))(2)] (X = S, R = Ph (2b); X = Se, R = Me (3b)). The compositions and structures of new compounds have been confirmed by NMR and IR spectroscopy, chemical analyses, and X-ray diffraction studies. Compounds 3b and 4a are the first crystallographically characterized metal complexes having selenone ligands coordinated to the metal centers. Preparation and X-ray study of analogous metal complexes of sulfone and selenone ligands allow, for the first time, tracking the structural changes induced by metal coordination. In addition, the X-ray structure of dimethyl selenone, Me(2)SeO(2) (3), an analogue of Me(2)SO(2), has been determined. Geometries of coordinated sulfone and selenones ligands have been compared with those of the corresponding "free" molecules.

Journal Article↗

PubMed2003

Synthesis, electrochemistry, and gas-phase photoelectron spectroscopic and theoretical studies of 3,6-bis(perfluoroalkyl)-1,2-dithiins.

3,6-bis(trifluoromethyl)- and 3,6-bis(pentafluoroethyl)-1,2-dithiin (1a,b), the first known perfluoroalkyl-substituted 1,2-dithiins, were synthesized from (Z,Z)-1,4-bis(tert-butylthio)-1,3-butadiene (2) to evaluate the effects of electron-withdrawing groups on the ionization and oxidation potentials of 1,2-dithiins. Analysis of the photoelectron spectra of 1a and 1b provided a basis for assigning orbital compositions. Ab initio calculations on these compounds showed that they adopt a twist geometry as does 1,2-dithiin (1c) itself. Cyclic voltammetric studies on 1a and 1b revealed a reversible oxidation followed by an irreversible oxidation at much more positive potentials than for 1,2-dithiin and 3,6-dimethyl-1,2-dithiin (1d). The oxidation potentials determined electrochemically do not correlate with the ionization potentials determined by photoelectron spectroscopy. This result supports the previously advanced hypothesis that there is a geometry change on electrochemical oxidation leading to a planar radical cation.

Journal Article↗

PubMed2003

Revised structure of a purported 1,2-dioxin: a combined experimental and theoretical study.

3,6-Bis(p-tolyl)-1,2-dioxin (1g) was suggested by Shine and Zhao as a product in an electron-transfer (ET) photochemical reaction. This photoproduct is instead shown to be (E)-1,4-di-p-tolylbut-2-ene-1,4-dione ((E)-4a). Ab initio and DFT calculations indicate that ring-closed 1,2-dioxin is thermodynamically far less stable than open-chain but-2-ene-1,3-dione. These calculations indicate that (E)-4a is formed via the cation radical of 1g, which sequentially isomerizes to a novel sigma-radical with an O,O 3e bond [(Z)-4a](+)(*), undergoes ET to give (Z)-4a, and then photoisomerizes to (E)-4a.

Cyclization↗

PubMed2003

Perthio- and perseleno-1,3-butadienes, -but-1-ene-3-ynes, and -[3]-cumulenes: one-step syntheses from 1,4-dilithio-1,3-butadiyne.

[reaction: see text] Treatment of 1,4-dilithio-1,3-butadiyne (1) with dichalcogenides RSSR or RSeSeR affords dithio- and diseleno-1,3-butadiynes (2, 3), perthio- and perseleno-[3]-cumulenes (4, 5), perthio- and perseleno-1,3-butadienes (6, 7), and/or perthio- and perseleno-but-1-ene-3-ynes (8, 9). The products can be controlled by stoichiometry and temperature, by the presence or absence of oxygen, and by choice of the "R" group. By X-ray crystallography, hexa(methylthio)-1,3-butadiene is highly twisted, with a torsion angle [Phi(CCCC)] of 84.7 degrees and an elongated C(2)-C(3) distance of 1.484(3) A.

Journal Article↗

PubMed2003

Small organoselenium molecules. 1. Dimethyl selenoxide: structure, complexation, and gas-phase transformation.

For the first time the structural characterization of dimethyl selenoxide coordinated to metal complexes has been performed confirming the Me(2)SeO arrangement assigned by spectroscopic techniques for the molecule in solution and solid state. The structure of Me(2)SeO is trigonal pyramidal with Se-O and Se-C bond lengths of 1.70 and 1.92 A, respectively, and sigma(X-Se-Y) = 301 degrees. As a ligand, dimethyl selenoxide was found to bind to the rhodium centers of various Lewis acidity strengths by using only its oxo functionality in both terminal and bridging fashions. This O-directed coordination preference contrasts with an ambidentate (-S and -O) binding character revealed by dimethyl sulfoxide upon formation of analogous donor-acceptor complexes. The study of dimethyl selenoxide in the gas phase at 135-140 degrees C resulted in a thermal degradation of this molecule. The major decomposition product has been entrapped by a metal complex and identified as dimethyl selenide. The isolation of the coordinated Me(2)Se fragment clearly demonstrates that the Me(2)SeO molecule is less thermally stable than Me(2)SO, which under similar reaction conditions shows no sign of decomposition at temperatures up to 160 degrees C.

Journal Article↗

PubMed1999

Synthesis and Structural Characterization of Neutral Silver(I) Complexes with Arenephosphinothiols. Crystal Structures of [Ag(4){2-(Ph(2)P)-6-(Me(3)Si)C(6)H(6)S}(4)] and [Ag(4){2-(Ph(2)PO)-6-(Me(3)Si)C(6)H(3)S}(4)].

Silver complexes of the anionic forms of 2-(diphenylphosphino)benzenethiol [2-(Ph(2)P)C(6)H(4)SH] (1), 2-(diphenylphosphino)-6-(trimethylsilyl)benzenethiol [2-(Ph(2)P)-6-(Me(3)Si)C(6)H(3)SH] (2), and 2-(diphenylphosphinyl)-6-(trimethylsilyl)benzenethiol [2-(Ph(2)PO)-6-(Me(3)Si)C(6)H(3)SH] (3) have been prepared by an electrochemical procedure and characterized by spectroscopic (IR, (1)H, (13)C, and (31)P NMR) methods, and ligand 3 and [Ag(4){2-(Ph(2)P)-6-(Me(3)Si)C(6)H(3)S}(4)] (5) and [Ag(4){2-(Ph(2)PO)-6-(Me(3)Si)C(6)H(3)S}(4)] (6) complexes were characterized by X-ray crystallographic techniques. Crystal data for 3: C(21)H(23)OPSSi, monoclinic, P2(1)/n, a = 11.3730(4) Å, b = 11.1562(4) Å, c = 17.1153(6) Å, beta = 103.961(1) degrees, V = 2107.4(1) Å(3), Z = 4, 2730 reflections with I(o) > 2sigma(I(o)), R = 0.0621. Crystal data for 5: C(84)H(88)Ag(4)P(4)S(4)Si(4), tetragonal, P4(2)2(1)2, a = 18.8454(7) Å, b = 18.8454(7) Å, c = 24.596(2) Å, V = 8735.1(7) Å(3), Z = 4, 4676 reflections with I(o) > 2sigma(I(o)), R = 0.0286. Crystal data for 6: C(90)H(97)Ag(4)N(3)O(4)P(4)S(4)Si(4), trigonal, P1, a = 13.4567(1) Å, b = 14.4148(2) Å, c = 14.8080(2) Å, alpha = 99.130(1) degrees, beta = 98.815(1) degrees, g = 114.211(1) degrees, V = 2509.38(5) Å(3), Z = 1, 6345 reflections with I(o) > 2sigma(I(o)), R = 0.0505. The [Ag(4){2-(Ph(2)P)-6-(Me(3)Si)C(6)H(3)S}(4)] (5) compound is tetranuclear with an array of four silver atoms bridged by four sulfur atoms. Each silver atom has a distorted trigonal [AgS(2)P] environment with each ligand acting as P,S bidentate S-bridging ligand. The [Ag(4)(2-(Ph(2)PO)-6-(Me(3)Si)C(6)H(3)S}(4)] (6) complex is also tetranuclear, but in this case two of the silver atoms are [AgO(2)S(2)] tetracoordinated and the other two Ag atoms are [AgS(2)] two coordinated.

Journal Article↗