X-ray diffraction analysis of spontaneously draining calcinosis in scleroderma patients.

OBJECTIVES: Calcium hydroxyapatite (HA) is reported to be the major constituent of soft tissue calcinosis in patients with scleroderma (systemic sclerosis, SSc). Mechanical stress and local tissue hypoxia are thought to be important in the pathogenesis of SSc calcinosis. We sought to analyse spontaneously draining material from calcinosis sites in SSc patients using X-ray diffraction (XRD). METHOD: With approval from our local Institutional Review Board (IRB), eligible SSc patients consented to submit their spontaneously draining calcinosis samples for XRD analysis. All patients met the American College of Rheumatology (ACR) criteria for definite SSc. XRD data were used to determine how much solid phase was present (e.g. HA vs. other calcium phosphate phases) and the percentage of crystalline components. Pertinent clinical data were collected. RESULTS: Draining calcinosis was submitted mostly from the hands of 10 female patients with advanced SSc, whose mean disease duration was 16 (range 9-29) years; six had diffuse cutaneous SSc and four had limited SSc. All 10 developed calcinosis later in their disease course; seven had extensive deposits affecting multiple sites. XRD confirmed that HA was the only crystalline material. However, HA was the minor component and most samples contained more than 50% organic material. Solid samples generally contained more HA and fluid samples contained HA in suspension. CONCLUSIONS: In this large series of SSc calcinosis analysis, XRD confirmed that HA was the only inorganic material that formed less than 50% of most draining samples. More research is needed to fully characterize and improve our understanding of calcinosis formation in SSc.

1-D infinite array of metalloporphyrin cages.

The reaction of Co(II) with 5,15-dipyridyl-10,20-diphenylporphyrin (H(2)DPyP) produces the first metal-organic coordination polymer supported by a trans meso-bifunctional porphyrin ligand. Formulated empirically as [Co(3)(DPyP)(3)] x 4DMF, this compound exhibits a ribbonlike coordination network consisting of tetranuclear metalloporphyrin cages. The DMF guest molecules fill the intra-ribbon cages as well as the inter-ribbon space. Evacuation of [Co(3)(DPyP)(3)] x 4DMF at 130 degrees C generates [Co(3)(DPyP)(3)] that retains crystallinity, as shown by its powder X-ray diffraction pattern, which is consistent with that of [Co(3)(DPyP)(3)] x 4DMF.

Chalcogen rich lanthanide clusters from halide starting materials (II): selenido compounds.

Lanthanides reduce mixtures of I(2) and PhSeSePh in THF, and the resultant heteroligand mixture reacts further with elemental Se in pyridine to give (THF)(6)Ln(4)I(2)(SeSe)(4)(mu(4)-Se).THF (Ln = Tm, Ho, Er, Yb). These selenium rich clusters contain a square array of Ln(III) ions connected through a single (mu(4)-Se) ligand. There are two I(-) ligands coordinating nonadjacent Ln(III) ions on the side of the cluster opposite the (mu(4)-Se), and the edges of the square are bridged by mu(2)-SeSe groups. The electronic spectrum of the Yb compound contains two absorption maxima that can tentatively be assigned as Se(2-) to Yb and SeSe to Yb charge-transfer absorptions, by comparison with the featureless absorption spectra of the Tm, Ho, and Er derivatives. With a 1/1/1/1 Yb/I/Ph(2)S(2)/Se stoichiometry, chalcogen rich compounds are not obtained, but instead, in Yb chemistry, the selenido cluster (THF)(10)Yb(6)Se(6)I(6) can be isolated in 51% yield. The molecular structure of this compound contains a Yb(4)Se(4) cubane fragment, with an additional Yb(2)Se(2) layer capping one face of the cube. Each Yb coordinates a terminal I(-). This intensely colored compound also has an absorption maximum in the visible spectrum. Upon thermolysis, the selenium rich compounds give Ln(2)Se(3) that is free of iodide contamination.

Chalcogen-rich lanthanide clusters: cluster reactivity and the influence of ancillary ligands on structure.

Ytterbium metal reacts with PhEEPh (E = S, Se, Te) and elemental Se in pyridine to give (pyridine)(8)Yb(4)(SeSe)(2)(Se)(2)(mu(2)-SPh)(2)(SPh)(2), (py)(8)Yb(4)Se(SeSe)(3)(SeSeSePh)(Se(0.38)SePh), and (py)(8)Yb(4)Se(SeSe)(3)(SeSeTePh)(SeTePh), respectively. The SePh and TePh compounds contain a square array of Ln(III) ions all connected to a central Se(2)(-) ligand. Three edges of the square are bridged by diselenide ligands, with the fourth SeSe unit coordinating to an EPh ligand that has been displaced from an inner Yb coordination sphere. Differences in the two compounds have their origin in the relative strength of the Yb-E(Ph) bond. In the TePh compound, there is a complete insertion of Se into the remaining Yb-Te(Ph) bond to give a terminal SeTePh ligand, while in the SePh compound there is a compositional disorder in the structure comprised of a terminal SePh ligand and a minor component that has Se inserted into the Yb-Se(Ph) bond to give a terminal SeSePh ligand. The thiolate compound differs dramatically, crystallizing as a rhombohedral array of four Yb(III) ions connected by a pair of mu(3)-Se(2)(-) ligands, with the edges of the rhombus spanned by alternating diselenide and SPh. The SPh coordinate directly to Yb(III) ions in terminal or bridging modes. Cluster interconversion is facile: (py)(4)Yb(SePh)(2) reduces (py)(8)Yb(4)Se(SeSe)(3)(SeSeSePh)(Se(0.38)SePh) to give the cubane cluster [(py)(2)YbSe(SePh)](4), and the cubane reacts with elemental Se to give (py)(8)Yb(4)Se(SeSe)(3)(SeSeSePh)(Se(0.38)SePh). Upon thermolysis, these compounds give YbSe(x)().

Synthesis of griseolic acid B by pi-face-dependent radical cyclization.

[reaction: see text]. Radical cyclization of 6 affords the bicyclic vinyl ether 9 with the appropriate stereochemistry for elaboration (seven steps) to griseolic acid B (1).

Assignment of the liposidomycin diazepanone stereochemistry.

The liposidomycins comprise a family of complex nucleoside antibiotics that inhibit bacterial peptidoglycan synthesis. Their structures (1, 2) feature nucleoside, ribofuranoside, diazepanone, and lipid regions. Several stereogenic centers remain unassigned, including three within the diazepanone region: C-6', C-2'", and C-3'". An intramolecular reductive amination reaction has been used to prepare model diazepanones. Analysis of 40 and two of its diastereomers by NMR spectroscopy, X-ray crystallography, and molecular modeling indicates a close relative configurational and conformational match between 40 and the liposidomycin diazepanone degradation product 43 and allows the assignment of stereochemistry of the natural products as either [C-6'(R), C-2'"(R), C-3'"(R)] or [C-6'(S), C-2'"(S), C-3'"(S)].

Heteroleptic lanthanide compounds with chalcogenolate ligands: reduction of PhNNPh/PhEEPh (E = Se or Te) mixtures with Ln (Ln = Ho, Er, Tm, Yb). Thermolysis can give LnN or LnE.

Lanthanide metals reduce mixtures of azobenzene and PhEEPh (E = Se or Te) in pyridine to give the bimetallic compounds [(py)2Ln(EPh)(PhNNPh)]2 (E = Se, Ln = Ho (1), Er (2), Tm (3), Yb (4); E = Te, Ln = Ho (5), Er (6), Tm (7), Yb (8)). The structures of [(py)2Er(mu-eta 2-eta 2-PhNNPh)(SePh)](2).2py (2) and [(py)2Ho(mu-eta 2-eta 2-PhNNPh)(TePh)](2).2py (5) have been determined by low-temperature single-crystal X-ray diffraction, and the nearly identical unit cell volumes of the remaining compounds indicate they are most likely isomorphous to 2 or 5. In all compounds, the Ln(III) ions are bridged by a pair of mu-eta 2-eta 2-PhNNPh ligands that, from the N-N bond length, have clearly been reduced to dianions. Charge is balanced by the single terminal EPh ligand on each Ln, and the coordination sphere is saturated by two pyridine donors to give seven coordinate metal centers. Thermal decomposition of 5 gives HoTe, 8 gives a mixture of YbN and YbTe, and 1 does not give a crystalline solid-state product. Crystal data (Mo K alpha, 153(2) K) are as follows: 2, monoclinic group P2(1)/n, a = 11.864(3) A, b = 14.188(2) A, c = 17.624(2) A, beta = 91.62(2) degrees, V = 2965(1) A3, Z = 4; 5, triclinic space group P1, a = 10.349(2) A, b = 17.662(4) A, c = 17.730(8) A, alpha = 75.82(3) degrees, beta = 74.11(3) degrees, gamma = 89.45(2) degrees, V = 3016(2) A3, Z = 2.

A spiro-linked pyrene-naphthoquinone.

The title molecule, 2'-pyrenylspiro[2, 3-dihydro-1H-cyclopenta[b]naphthalene-2,5'-1',3'-dioxane]-4,9-dione, C(32)H(22)O(4), contains an electron-donating pyrene group spiro-linked to an electron-accepting naphthoquinone. The molecules are V-shaped in profile and stack to form columns along b with alternating, approximately coplanar, pyrene and naphthoquinone fragments. Intermolecular contacts within a column are consistent with some degree of pi contact and possible long-range delocalization. Individual columns form a herringbone pattern when the crystal is viewed along b.

Divalent samarium compounds with heavier chalcogenolate (EPh; E = Se, Te) ligands.

Crystalline coordination complexes of Sm(EPh)2 (E = Se, Te) are described. The selenolate compound Sm(SePh)2 is unstable in solution, but a divalent selenolate can be prepared and isolated when precisely 1 equiv of Zn(SePh)2 is present to form heterometallic [(THF)3Sm(mu 2-SePh)3Zn(mu 2-SePh)]n (1). This compound is a 1D coordination polymer with alternating Sm(II) and Zn(II) ions connected by an alternating (1,3) number of bridging selenolate ligands and three THF ligands bound to each Sm(II) ion. The tellurolate Sm(TePh)2 forms a stable pyridine coordination compound (py)5Sm(TePh)2 (2) that is isostructural with known Eu and Yb benzenetellurolates. Both compounds were characterized by conventional spectroscopic methods. Polymer 1 was characterized by low-temperature single-crystal X-ray diffraction, and the unit cell of the tellurolate was determined. Crystal data (Mo K alpha, 153(5) (K) are as follows. 1: monoclinic space group P21, a = 10.666(2) A, b = 16.270(3) A, c = 12.002(3) A, beta = 114.81(2) degrees, Z = 2.2: orthorhombic space group Pbca, with a = 13.865(3) A, b = 16.453(5) A, c = 31.952(7) A, Z = 8.

Early- and Late-Lanthanide Pyridinethiolates: Synthesis, Redox Stability, and Structure.

The early and late lanthanides form stable complexes with the pyridinethiolate (2-S-NC(5)H(4), or SPy) ligands. The Ce compound Ce(SPy)(3) is relatively insoluble in neutral organic donor solvents such as THF or pyridine but can be solubilized by the addition of [PEt(4)][SPy] to form the orange homoleptic cerium thiolate [PEt(4)][Ce(SPy)(4)] (1). Low-temperature structural characterization of 1 showed that the complex is isostructural with the known Eu(III) derivative. Further oxidation of Ce(III) with dipyridyl disulfide does not occur. Molecular 1 is colored due to a low-energy f(1)-to-d(1) promotion. As the size of the lanthanide ion decreases, the solubility of neutral Ln(SPy)(3) appears to increase. Colorless [PEt(4)][Ln(SPy)(4)] (Ln = Ho (2), Tm (3)) can also be isolated by fractional crystallization, and the compounds are isostructural with the Ce and Eu derivatives. The neutral complexes of Ho and Tm are also slightly soluble in acetonitrile and dimethoxyethane and very soluble in pyridine. Both divalent and trivalent Yb complexes of the pyridinethiolate ligand dissolve in and crystallize from pyridine. Divalent Yb(SPy)(2) crystallizes as the pentagonal bipyramidal molecule (py)(3)Yb(SPy)(2) (4). One pyridine nitrogen and the four donor atoms of the two pyridinethiolate ligands are bound in equatorial positions, and two neutral pyridine ligands occupy the axial sites. The Yb(III) compound crystallizes readily from pyridine as molecular 8-coordinate (py)(2)Yb(SPy)(3) (5). Compounds 4 and 5 are intensely colored; 4 has a visible Yb(II)-to-pyridine charge transfer excitation that is virtually identical in energy to the analogous excitation in SmI(2)(py)(4), while 5 has a visible S-to-Yb charge transfer absorption. Crystal data (Mo Kalpha, 153(5) K) are as follows: 1, monoclinic space group P2/n, a = 15.118(6) Å, b = 16.117(4) Å, c = 26.443(7) Å, beta = 90.14(3) degrees, Z = 4; 4, monoclinic space group Cc, a = 10.588(1) Å, b = 16.810(3) Å, c = 14.833(5) Å, beta = 109.12(2) degrees, Z = 4; 5, monoclinic space group P2(1)/n, a = 9.672(2) Å, b = 16.293(4) Å, c = 19.214(3) Å, beta = 101.51(2) degrees, Z = 4.

Pyridineselenolate Complexes of Copper and Indium: Precursors to CuSe(x)() and In(2)Se(3).

The pyridineselenolate (2-Se-NC(5)H(4), (SePy)) and the 3-(trimethylsilyl)pyridineselenolate (3-Me(3)Si-2-Se-NC(5)H(4) (SePy)) ligands form air-stable homoleptic coordination compounds of Cu(I) { [Cu(SePy)](4) (1) and [Cu(SePy)](4) (2)} and In(III) {In(SePy)(3) (3) and In(SePy)(3) (4)}. Mass spectroscopic characterization of the Cu(I) compounds indicated a tetrametallic core, and this was confirmed with a single-crystal X-ray structural characterization of crystalline 1 and 2, which both contain a tetrametallic cluster of Cu(I) ions bound to two doubly bridging Se atoms and a pyridine nitrogen. The Cu coordination sphere is completed with two strong Cu-Cu bonds and one weaker Cu-Cu interaction. The indium compounds 3 and 4 are each distorted fac-octahedral molecules with chelating SePy ligands. These compounds are useful low-temperature precursors to the binary selenides. Both 3 and 4 sublime intact; 3 thermally decomposes to give In(2)Se(3). The Cu clusters do not sublime intact but still decompose to give metal selenide phases: 2 decomposes to give pure alpha-CuSe at low temperatures and increasing amounts of Cu(2)(-)(x)()Se at elevated temperatures, while 3 decomposes to give a mixture of CuSe phases at all temperatures. Crystal data (Mo Kalpha: 1, 153(5) K; 2-4, 293(2) K) are as follows: 1, monoclinic space group C2/c, a = 20.643(5) Å, b = 16.967(2) Å, c = 16.025(2) Å, beta = 114.16(2) degrees, Z = 8; 2, tetragonal space group I4(1)/a, a = 14.756(3) Å, c = 19.925(3) Å, Z = 4; 3, trigonal space group P&thremacr;c1, a = 13.352(2) Å, c = 13.526(2) Å, Z = 4; 4, monoclinic space group P2(1)/c, a = 9.793(1) Å, b = 20.828(6) Å, c = 16.505(1) Å, beta = 96.69(1) degrees, Z = 4.

Crystal Structure, Electrical Transport, and Magnetic Properties of Niobium Monophosphide.

Large single crystals of NbP have been prepared. A single-crystal X-ray diffraction study shows that it crystallizes in tetragonal symmetry with space group I4(1)md (No. 109) and lattice parameters a = 3.3324(2) Å, c = 11.3705(7) Å, and Z = 4. A full matrix least-squares refinement based on a unique data set of 285 reflections (I> 2sigma(I)) yielded R(F) = 0.017 and R(w)(F(2)) = 0.046 for nine variables. The unit cell consists of one unique Nb and one P, each in trigonal prismatic coordination with the other element. There are two short and four long bond distances of Nb-P. The Nb-Nb bond distances are significantly shorter than R(c) = 4.09 Å, the critical distance required for good Nb-Nb 4d orbital overlap for niobium metal-metal bonds. NbP shows metallic behavior with rho = 4.5 x 10(-)(5) Omega cm at room temperature. Magnetic susceptibility measurements on a collection of randomly oriented single crystals indicate very weak Pauli paramagnetism ( approximately 10(-)(5) emu/mol). A discussion of the structure as well as the physical properties of NbP compared with those of previous results are presented. The band structure of NbP based on the extended Hückel (tight-binding) calculations is presented along with an analysis that reveals that the valence band is built up from three center bonds localized within Nb(3) triangles.

Pyridineselenolate Complexes of Tin and Lead: Sn(2-SeNC(5)H(4))(2), Sn(2-SeNC(5)H(4))(4), Pb(2-SeNC(5)H(4))(2), and Pb(3-Me(3)Si-2-SeNC(5)H(3))(2). Volatile CVD Precursors to Group IV-Group VI Semiconductors.

Pyridineselenolate forms stable homoleptic coordination compounds of Sn(II), Sn(IV), and Pb(II). The complexes can be prepared either by metathesis or by insertion of the metal into the Se-Se bond of dipyridyl diselenide, and they are soluble in coordinating solvents such as pyridine. Isolation of the Pb(II) complex from both Pb(0) and Pb(IV) starting materials indicates that the pyridineselenolate ligand cannot stabilize Pb(IV). The compounds all sublime intact and decompose at elevated temperatures: the divalent complexes give MSe (M = Sn, Pb), while the Sn(IV) compound delivers SnSe(2). In order to isolate a crystalline Pb compound, the 3-trimethylsilyl-2-pyridineselenolate ligand was prepared. Attachment of the Me(3)Si functional group increases compound solubility, and leads to the isolation of crystalline Pb(3-Me(3)Si-2-SeNC(5)H(4))(2). The structure of [Sn(2-SeNC(5)H(4))(2)](2) (1) was determined by single-crystal X-ray diffraction and shown to be a dimer, with one chelating pyridineselenolate per Sn(II) and a pair of pyridineselenolates that asymmetrically span the two metal centers to form an eight membered (-Sn-Se-C-N-Sn-Se-C-N-) ring, with weak Sn-Se interactions connecting the dimeric units. Crystal data for 1 (Mo Kalpha, 298(2) K): orthorhombic space group Pbca, a = 8.214(1) Å, b = 21.181(3) Å, c = 14.628(2) Å.

Platinum(II) triamine complexes: cis-[PtCl(NH3)2(C10H13N5O5)]NO3.2H2O and [PtCl(C2H8N2)(C4H6N2)]NO3.

The structures of cis-diamminechloro(guanosine-N7)-platinum(II) nitrate dihydrate, cis-[PtCl(NH3)2-(C10H13N5O5)]NO3.2H2O, (I), and chloro(ethylenediamine)(1-methylimidazole-N3)platinum(II) nitrate, [PT-(C2H8N2)(C4H6N2)Cl]NO3, [PtCl(en)(1-MeIm)]NO3, (II), were determined by single-crystal X-ray diffraction. The former complex crystallized in the orthorhombic system and the latter in the monoclinic system. In compound (I), water molecules were found to connect the metal complex with the nitrate counter ions via hydrogen bonding.

Structure-function analysis of antimicrotubule dinitroanilines against promastigotes of the parasitic protozoan Leishmania mexicana.

Although leishmaniasis is a major tropical disease, the currently available drugs are toxic and inadequate. We show that the antimicrotubule herbicide trifluralin has antileishmania activity. The present study aimed at deducing the relationship between the structure of the molecule and its antiprotozoan activity. Nine dinitroanilines, all of which were analogs of trifluralin, were compared. We found that pendimethalin was 2.5-fold more potent than trifluralin, and the higher efficacy may be correlated with molecular structural features that increase the accessibility to one nitro group. This association was further supported by molecular modeling. Moreover, trifluralin samples from two sources differed in their activities by more than threefold, and gas column chromatography showed that impurities were present in the more potent sample.

Expression of rat L-FABP in mouse fibroblasts: role in fat absorption.

Fatty acid-binding proteins (FABP) are abundant cytosolic proteins whose levels is responsive to nutritional, endocrine, and a variety of pathological states. Although FABPs have been investigated in vitro for several decades, little is known of their physiological function. Liver L-FABP binds both fatty acids and cholesterol. Competitive binding analysis and molecular modeling studies of L-FABP indicate the presence of two ligand binding pockets that accommodate one fatty acid each. One fatty acid binding site is identical to the cholesterol binding site. To test whether these observations obtained in vitro were physiologically relevant, the cDNA encoding L-FABP was transfected into L-cells, a cell line with very low endogenous FABP and sterol carrier proteins. Uptake of both ligands did not differ between control cells and low expression clones. In contrast, both fatty acid uptake and cholesterol uptake were stimulated in the high expression cells. In high expression cells, uptake of fluorescent cis-parinaric acid was enhanced more than that of trans-parinaric acid. This is consistent with the preferential binding of cis-fatty acids to L-FABP but in contrast to the preferential binding of trans-parinaric acid to the L-cell plasma membrane fatty acid transporter (PMFABP). These data show that the level of cytosolic fatty acids in intact cells can regulate both the extent and specificity of fatty acid uptake. Last, sphingomyelinase treatment of L-cells released cholesterol from the plasma membrane to the cytoplasm and stimulated microsomal acyl-CoA: cholesteryl acyl transferase (ACAT). This process was accelerated in high expression cells. These observations show for the first time in intact cells that L-FABP, a protein most prevalent in liver and intestine where much fat absorption takes place, may have a role in fatty acid and cholesterol absorption.

Identification of the sites of modification on bovine carbonic anhydrase II (BCA II) by the salt-bridge reagent cyanogen, C2N2.

The hydrolase activities of bovine carbonic anhydrase B (BCA II carbonate hydrolyase, EC 4.2.1.1) were modified by cyanogen (C2N2, N identical to C-C identical to N, ethanedinitrile) with decreases in Vmax of as much as 99%. This was not accompanied by a reduction in hydrolyase activity. These changes were not reversed at lower pH values but the enzymatic activity was restored by incubation at pH 10. 14C-labeled glycine ethyl ester ([14C]GEE) specifically and covalently bound to the cyanogen-treated BCA II, as verified by HPLC and 14C monitoring. It was shown that sites of cyanogen-introduced modifications in BCA II could be effectively labeled and identified by incubation with the nucleophile [14C]GEE. Three radiolabeled tryptic peptides from BCA II arising from a labeling process designed to study cyanogen-induced modifications leading to nucleophile labile covalent bonds have been isolated. The residues identified by [14C]GEE labeling were Asp-34, Glu-117 and Asp-152. Three moieties attached to the omega-carboxyls by C2N2 were tentatively identified by molecular modeling; they were Arg-111, His-107 and/or His-119 and Ser-216, respectively. The use of C2N2 afforded a means to compare the salt bridges in two species and showed that two of three were not conserved.