Acute Effect of Orally Administered Gallium Arsenide,Gallium Nitrate and Disodium Arsenate on Heme Synthesis in Male and Female Mice

Gallium arsenide (GaAs), gallium nitrate and disodium arsenate were each administered orally to mice of both sexes (Jcl:ICR strain) at varying dosage levels and examined for their effects on the heme biosynthetic enzyme system in the spleen, liver, kidney and peripheral blood. The results indicate that the areas most affected by administration of gallium nitrate or disodium arsenate were enzymes in the hematogenous cells of mouse spleen. In mice of the disodium arsenate-treated groups δ-aminolevulinic acid synthase (ALAS, EC 2.3.1.37), the first enzyme in the heme biosynthetic pathway and the rate-limiting enzyme for heme synthesis, δ-aminolevulinic acid dehydratase (ALAD, EC 4.2.1.24) and porphobilinogen deaminase (PBGD, EC 4.3.1.8) activities in the spleen were markedly depressed in a dose-dependent fashion. A similar, but apparently less marked, reduction in these enzyme activities in the spleen was also observed in the gallium nitrate-treated groups. The effects of these treatments were more conspicuous in female than in male mice. An in vitro experiment demonstrated that activities of purified ALAS, ALAD and PBGD were not inhibited to any noticeable extent by arsenic compounds. These results suggest that disodium arsenate may strongly inhibit heme biosynthesis in mouse spleen.     

Bergenin monohydrate from the rhizomae of Astilbe chinensis

The title compound, 4‐methoxy‐2‐[(1S,2R,3S,4S,5R)‐3,4,5,6‐tetrahydro‐3,4,5‐tri­hydroxy‐6‐(hydroxy­methyl)‐2H‐­pyran‐2‐yl]‐α‐resorcylic acid δ‐lactone monohydrate, C₁₄H₁₆O₉·H₂O, is a C‐glucoside of 4‐O‐methylgallic acid which has antiasthmatic, antitussive, anti‐inflammatory, antifungal, anti‐HIV and antihepatotoxic activity. The mol­ecule is composed of three six‐membered rings: an aromatic ring, a glucopyran­ose ring and an annellated δ‐lactone ring. The glucopyran­ose ring exhibits only small deviations from an ideal chair conformation. The annellated δ‐lactone ring possesses the expected half‐chair conformation. There is one intra‐ and six intermolecular hydrogen bonds which form an extensive hydrogen‐bonding network within the crystal.     

X‐ray investigations of bicyclic α‐methyl­ene‐δ‐valerolactones. III. trans‐(4aR,8aR)‐4a‐Methoxy‐3‐methyleneperhydro­chromen‐2‐one

The title compound, C₁₁H₁₆O₃, adopts a conformation in which the δ‐valerolactone and cyclo­hexane rings are almost coplanar with one another. The β‐methoxy substituent occupies an axial position with respect to the cyclo­hexane ring. The δ‐valerolactone moiety adopts a half‐chair arrangement, while the cyclo­hexane ring exists in a chair conformation.     

X‐ray investigations of bicyclic α‐methyl­ene‐δ‐valerolactones. II. (4aS,8aS)‐4a‐Methyl‐3‐methyl­eneper­hydro­chromen‐2‐one

The title compound, C₁₁H₁₆O₂, adopts a semifolded conformation with the δ‐lactone and cyclo­hexane rings almost perpendicular to one another. The β‐methyl substituent occupies an axial position with respect to the cyclo­hexane ring. The δ‐lactone moiety adopts a slightly distorted half‐chair arrangement, while the cyclo­hexane ring exists in an almost ideal chair conformation.     

(4R,4aR,6S,7S,7aS)‐6‐Hydro­xy‐7‐hy­droxy­methyl‐4‐methyl­per­hydro­cyclo­penta­[c]­pyran‐1‐one chloro­form solvate from Valeriana laxiflora

The structure of an iridolactone isolated from Valeriana laxiflora was established as (4R,4aR,6S,7S,7aS)‐6‐hydroxy‐7‐hydroxy­methyl‐4‐methyl­per­hydro­cyclo­penta­[c]­pyran‐1‐one chloro­form solvate, C₁₀H₁₆O₄·CHCl₃. The two rings are cis‐fused. The δ‐lactone ring adopts a slightly twisted half‐chair conformation with approximate planarity of the lactone group and the cyclo­pentane ring adopts an envelope conformation. The hydroxy group, the hydroxymethyl group and the methyl group all have β orientations. The absolute configuration was determined using anomalous dispersion data enhanced by the adventitious inclusion of a chloro­form solvent mol­ecule. Hydro­gen bonding, crystal packing and ring conformations are discussed in detail.     

The epimeric 9‐oxobicyclo[3.3.1]nonane‐3‐carboxylic acids: hydrogen‐bonding patterns of the endo acid and the lactol of the exo acid

The two δ‐keto carboxylic acids of the title, both C₁₀H₁₄O₃, are epimeric at the site of carboxyl attachment. The endo (3α) epimer, (I), has its keto‐acid ring in a boat conformation, with the tilt of the carboxyl group creating conformational chirality. The mol­ecules form hydrogen bonds by centrosymmetric pairing of carboxyl groups across the corners of the chosen cell [O⃛O = 2.671 (2) Å and O—H⃛O = 179 (2)°]. Two close intermolecular C—H⃛O contacts exist for the ketone. The exo (3β) epimer exists in the closed ring–chain tautomeric form as the lactol, 8‐hydroxy‐9‐oxatri­cyclo­[5.3.1.0^3,8]­undecan‐10‐one, (II). The mol­ecules have conformational chirality, and the hydrogen‐bonding scheme involves intermolecular hydroxyl‐to‐carbonyl chains of mol­ecules screw‐related in b [O⃛O = 2.741 (2) Å and O—H⃛O = 177 (2)°].     

Cs[Si3O6(OH)] and Rb[Si2O4(OH)]: two novel phyl­losilicates

The crystal structures of two novel phyl­losilicates with compositions Cs[Si₃O₆(OH)] (caesium hydroxo­hexa­oxotetra­otri­silicate) and Rb[Si₂O₄(OH)] (rubidium hydroxo­hexa­oxotetrao­di­silicate) have been characterized by X‐ray diffraction. The topology of the caesium phyl­losilicate silica sheet consists of interconnected four‐ and six‐membered rings and thus differs from all of the previously reported phyl­losilicates. The topology of the rubidium phyl­losilicate silica sheet consists of six‐membered rings only, in boat conformations, resulting in a corrugated sheet similar to that observed in δ‐Na₂Si₂O₅. Both of the title compounds exhibit the characteristic sandwich structure of sheet silicates, with the Cs atom ninefold coordinated and the Rb atom eightfold coordinated to the framework O atoms.     

Three complexes of bis(N‐methyl­benzo­hydro­xamato‐O,O′)copper(II)

The first single‐crystal studies of three bis‐transoid Cu–hydrox­amate salts, bis(3‐methoxy‐4,N‐dimethyl­benzo­hydrox­amato‐O,O′)copper(II), [Cu(C₁₀H₁₂NO₃)₂], bis(4‐chloro‐N‐methyl­benzo­hydro­xamato‐O,O′)copper(II), [Cu­(C₈­H₇­Cl­NO₂)₂], bis(N‐methyl‐3,5‐di­nitro­benzo­hydro­xamato‐O,O′)copper(II)–chloro­form (1/2), [Cu­(C₈­H₆­N₃O₆)₂]·­2CHCl₃, are presented. The Cu atom in each of the title compounds sits at a center of inversion and displays a nearly square‐planar geometry with the hydro­xamate‐O atoms connected to it in a syn configuration. The N atoms are in a transoid configuration. Each five‐membered Cu–hydro­xamate ring is planar, thus providing evidence that a planar N atom is present in each ring. The phenyl groups are twisted with respect to the hydro­xamate group by ～40–54°. The angular strain of the sp² carbonyl oxy­gen is significant (～10° from ideal).     

tert‐Butyl (6S)‐4‐hydroxy‐6‐isobutyl‐2‐oxo‐1,2,5,6‐tetra­hydropyridine‐1‐carboxyl­ate and tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxopiperidine‐1‐carboxyl­ate

X‐ray studies reveal that tert‐butyl (6S)‐6‐iso­butyl‐2,4‐dioxo­piperidine‐1‐carboxyl­ate occurs in the 4‐enol form, viz. tert‐butyl (6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo‐1,2,5,6‐tetra­hydropyri­dine‐1‐carboxyl­ate, C₁₄H₂₃NO₄, when crystals are grown from a mixture of di­chloro­methane and pentane, and has an axial orientation of the iso­butyl side chain at the 6‐position of the piperidine ring. Reduction of the keto functionality leads predominantly to the corresponding β‐hydroxy­lated δ‐lactam, tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo­piperidine‐1‐car­boxyl­ate, C₁₄H₂₅NO₄, with a cis configuration of the 4‐hydroxy and 6‐iso­butyl groups. The two compounds show similar molecular packing driven by strong O—H⋯O=C hydrogen bonds, leading to infinite chains in the crystal structure.     

9‐(1‐Acetoxy­ethyl­idene)­fluorene (`diacetyl­fluorene'), a by‐product from the acetyl­ation of 9‐fluorenyl­lithium

Treatment of 9‐fluorenyl­lithium with acetyl chloride produces 9‐acetyl­fluorene, (I), and several by‐products, among which is `di­acetyl­fluorene', now characterized definitively as 9‐(1‐acetoxy­ethyl­idene)­fluorene [IUPAC name: (1‐fluoren‐9‐yl­idene­)ethyl acetate], (II), C₁₇H₁₄O₂, derived from acetyl­ation of initially formed (I). Various parameters disclose substantial structural distortion within (II) emanating from A^(1,3) strain associated with the 9‐(acetoxy­ethyl­idenyl)­fluorene system.     

Compositional disorder in trans‐[RhBr0.26Cl0.74H(PMe3)4][B(1,2‐O2C6Br4)]·CH2Cl2

The structure of trans‐(bromo/­chloro)­hy­drido­tetra­kis­(tri‐me­thyl­phos­phine)­rhod­ium(III) bis­(tetra­bromo­pyro­catechol‐ato‐O,O′)­borate dichloromethane solvate, [RhCl_0·74Br_0·26H‐(C₃­H₉­P)₄]­(C₁₂­BBr₈­O₄)·­CH₂Cl₂, is reported. The Rh^III com­plex shows bromine/chlorine compositional disorder with a trans arrangement of the hydride and halide ligands. The anion has approximate D_2d symmetry, with a central spiro‐B atom distorted from regular tetrahedral geometry by the small chelating O—B—O angles.     

2‐Acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamides: functionalized amino acid anticonvulsants

In the crystal structure of 2‐acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamide (3L), C₁₂H₁₇N₃O₃, the 2‐acetyl­amino­acetamide moiety has a linearly extended conformation, with an inter­planar angle between the two amide groups of 157.3 (1)°. In 2‐acetamido‐N‐benz­yl‐2‐[meth­oxy(meth­yl)­amino]­acetamide (3N), C₁₃H₁₉N₃O₃, the planes of the two amide groups inter­sect at an angle of 126.4 (4)°, resulting in a chain that is slightly more bent. The replacement of the methoxy­amino H atom of 3L with a methyl group to form 3N and concomitant loss of hydrogen bonding results in some positional/thermal disorder in the meth­oxy­(methyl)­amino group. In both structures, in addition to classical N—H⋯O hydrogen bonds, there are also weak non‐standard C—H⋯O hydrogen bonds. The hydrogen bonds and packing inter­actions result in planar hydro­philic and hydro­phobic areas perpendicular to the c axis in 3L and parallel to the ab plane in the N‐meth­yl derivative. Stereochemical comparisons with phenytoin have identified two O atoms and a phenyl group as mol­ecular features likely to be responsible for the anticon­vulsant activities of these compounds.     

Synthesis of various end‐functionalized polyesters by controlled/living ring‐opening polymerization of lactones using pentafluorophenylbis(triflyl)methane

The ring‐opening polymerizations (ROPs) of ε‐caprolactone (ε‐CL) and δ‐valerolactone (δ‐VL) with pentafluorophenylbis(triflyl)methane (C₆F₅CHTf₂) as the organocatalyst and alcohol initiators were carried out. For the ROP using 3‐phenyl‐1‐propanol (PPA) as the initiator in CH₂Cl₂ at room temperature with the [ε‐CL or δ‐VL]₀/[PPA]₀/[C₆F₅CHTf₂] ratio of 50/1/0.1, the polymerization homogeneously proceeded to afford poly(ε‐caprolactone) (PCL) and poly(δ‐valerolactone) (PVL) having narrow polydispersity indices. The molecular weights of the obtained polymers determined from ¹H NMR spectra showed good agreement with those estimated from the initial ratio of [ε‐CL or δ‐VL]₀/[PPA]₀ and monomer conversions. The ¹H NMR, size exclusion chromatography, and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry measurements strongly indicated that PCL and PVL possessed the 3‐phenylpropoxy group as the α‐chain‐end and the hydroxy group as the ω‐chain‐end. In addition, the controlled/living nature for the C₆F₅CHTf₂‐catalyzed ROP of lactones was confirmed by kinetic and chain‐extension experiments. The block copolymerization of PCL and PVL successfully proceeded to afford PCL‐b‐PVL and PVL‐b‐PCL. In addition, various end‐functionalized PCLs and PVLs with narrow molecular weight distributions were synthesized by the ROP of ε‐CL and δ‐VL using functional initiators, such as 6‐azido‐1‐hexanol, 2‐hydroxyethyl methacrylate, propargyl alcohol, N‐(2‐hydroxyethyl)maleimide, 4‐vinylbenzyl alcohol, 5‐hexen‐1‐ol, and 5‐norbornene‐2‐methanol. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

A hydro­gen-bonded `trimer' of two symmetric dipyridones

The isomers 3,3′-(1,2-ethynediyl)­bis­(2-pyridone), (I), and 6,6′-(1,2-ethyne­diyl)­bis­(2-pyridone), (II), were designed to form a hydrogen-bonded pair through alignment of their complementary cyclic lactam moieties. Instead, an equimolar mixture of (I) and (II) dissolved in methanol produced crystals of 3,3′-(1,2-ethynediyl)­bis(2-pyridone)–6,6′-(1,2-ethynediyl)­bis(2-py­ri­done)–methanol (1/2/2), 0.5C₁₂H₈N₂O₂·C₁₂H₈N₂O₂·CH₄O, in which one mol­ecule of (I), situated at a center of symmetry, is hydrogen bonded to two mol­ecules of (II) and to two mol­ecules of methanol.     

[Fe(C12H8N3O2)Cl2(ROH)], with R = Me and Et

The title octahedral complexes, [bis(pyridine‐2‐carbonyl)­amin­ate]­di­chloro­(methanol)­iron(III), [Fe(C₁₂H₈N₃O₂)­Cl₂‐(CH₄O)], and [bis­(pyri­dine‐2‐carbonyl)­amin­ate]­di­chloro‐(ethanol)­iron(III), [Fe­(C₁₂H₈N₃O₂)Cl₂(C₂H₆O)], both crystallize in space group and have similar structures. Mono­anionic bpca^? [bis(pyridine‐2‐carbonyl)­amin­ate] acts as a planar tridentate ligand in both cases. Coordination bond distances are in the range typical of high‐spin Fe^III complexes. Carbon–oxygen distances are typical of a C=O double bond suggesting the negative charge of the bpca^? ligand is localized on the central N atom.     

Two biologically active thio­phene‐3‐carbox­amide derivatives

The compounds 2‐{[(E)‐(4‐methoxy­phenyl)­methyl­ene]­amino}‐N‐(3‐methyl­phenyl)‐4,5,6,7‐tetra­hydro‐1‐benzo­thio­ph­ene‐3‐carbox­amide, C₂₄H₂₄N₂O₂S, (I), and N‐(4‐meth­yl­phenyl)‐2‐{[(E)‐(4‐methyl­phenyl)­methyl­ene]­amino}‐4,5,6,7‐tetra­hydro‐1‐benzo­thio­phene‐3‐carbox­amide, C₂₄H₂₄N₂OS, (II), show antibacterial and antifungal activities. The m‐toluidine ring in (I) and the p‐toluidine ring in (II) are coplanar with their respective thio­phene rings. In (I), an intermolecular C—H⋯O hydrogen bond is present, whereas (II) does not exhibit any significant intermolecular interactions. However, in both compounds, an intramolecular N—H⋯N hydrogen bond forms a pseudo‐six‐membered ring, thus locking the molecular conformation and eliminating conformational flexibility.     

Complexes of mixed silicon halides with 4‐picoline

The reaction products of an addition reaction of five different silicon tetrahalides with the aromatic nitro­gen base 4‐methyl­pyridine are presented. The following five structures are isomorphous: (I) tetra­chloro­bis(4‐methyl­pyridine)­silicon, C₁₂H₁₄­Cl₄­N₂Si, (II) bromo­tri­chloro­bis(4‐methyl­pyridine)­silicon, C₁₂H₁₄­Br­Cl₃N₂Si, (III) di­bromo­di­chloro­bis(4‐methyl­pyridine)­silicon, C₁₂H₁₄­Br₂­Cl₂N₂Si, (IV) tri­bromo­chloro­bis(4‐methyl­pyridine)­silicon, C₁₂H₁₄Br₃­Cl­N₂Si, and (V) tetra­bromo­bis(4‐methyl­pyridine)­silicon, C₁₂H₁₄Br₄N₂Si. The mol­ecules of (I) and (V), with D_2h symmetry, have crystallographic C_2h symmetry, while the molecules of (II), (III) and (IV) have a lower molecular symmetry, but as a result of the disorder of the halogen ligands, they appear to be of the same crystallographic symmetry. The environment around the Si atom can be described as a slightly distorted octahedron with the methyl­pyridine ligands occupying axial positions and the four halogen ligands in the equatorial plane. In spite of the different substitution pattern of the silicon centre, there are only insignificant differences between these five structures.     

Hydrogen bonding in two salts of 3‐methylthio‐4‐(propargylthio)quinoline

In 3‐methyl­thio‐4‐(propargyl­thio)­quinolinium chloride monohydrate, C₁₃H₁₂NS₂⁺·Cl^?·H₂O, and 3‐methyl­thio‐4‐(propargyl­thio)­quinolinium tri­chloro­acetate, C₁₃H₁₂­NS₂⁺·­C₂Cl₃O₂^?, the terminal alkyne group forms C[triple‐bond]C—H?O hydrogen bonds of favourable geometry. The conformation of the flexible propargyl­thio group is different in the two structures.     

Hydrogen-bonded sheets in the 1:1 salt of tet-b and trimesic acid

Tet-b (racemic 5,5,7,12,12,14-hexa­methyl-1,4,8,11-tetra­aza­cyclo­tetra­decane, C₁₆H₃₆N₄) and trimesic acid (1,3,5-benzene­tri­carboxylic acid, C₉H₆O₆) form a salt partially solvated by both water and methanol, i.e. 5,5,7,12,12,14-hexa­methyl-1,4,8,11-tetra­aza­cyclo­tetra­decane–1,3,5-benzene­tri­carboxyl­ic acid–methanol–water (1/1/0.78/1.12), C₁₆H₃₈N₄²⁺·C₉H₄O₆²⁻·0.78CH₄O·1.12H₂O. The anions are linked by O—H⃛O hydrogen bonds [O⃛O 2.442 (4) and 2.458 (4) Å; O—H⃛O 170 and 171°] into zigzag chains; orientationally disordered cations are linked to the anion chains by means of N—H⃛O hydrogen bonds [major orientation: N⃛O 2.695 (3)–3.071 (4) Å, N—H⃛O 148–179°; minor orientation: N⃛O 2.75 (2)–3.34 (2) Å, N—H⃛O 147–170°] and link the chains into sheets. The solvent mol­ecules are all disordered, but appear to play no significant structural role apart from space filling.     

Methoxy‐ether and crown‐ether ­derivatives of tetrahomodioxa‐ and octahomotetraoxacalix­[4]­arenes

Three methoxy­‐ether and one methoxy‐­ether/crown‐ether derivatives of p‐tert‐butyl­tetrahomodioxa‐ and p‐R‐octahomo­tetraoxacalix­[4]­arenes (R = methyl, tert‐butyl, H) have been investigated. The first three compounds, 7,15,21,27‐tetra‐tert‐butyl‐29,30,31,32‐tetra­methoxy‐3,11‐dioxapenta­cyclo­[23.3.­1.1^5,9.1^13,17.1^19,23]­ditriaconta‐1(29),5,7,­9(30),­13,15,‐17(31),­19,21,23(32),25,27‐dodecaene, C₅₀H₆₈O₆, 33,34,35,36‐tetra­methoxy‐7,15,23,31‐tetra­methyl‐3,11,19,27‐tetra­oxa­penta­cyclo[27.3.1.1^5,9.1^13,17.1^21,25]­hexa­tri­aconta‐1(33),5,7,9(34),13,15,­17(35),21,23,25(36),29,31‐dodecaene, C₄₀H₄₈O₈, and 7,23‐di‐tert‐butyl‐33,34,35,36‐tetra­methoxy‐3,11,19,27‐tetraoxapenta­cyclo­[27.3.1.1^5,9.1^13,17.1^21,25]­hexatriaconta‐1(33),5,7,9(34),13,15,­17(35),‐ 21,23,25(36),29,31‐dodecaene, C₄₄H₅₆O₈, in the partial‐cone or 1,2‐alternate conformations, present the common feature of methoxy‐­ether self‐inclusion, while the fourth, 42,43‐di­methoxy‐7,15,23,31‐tetra­methyl‐3,11,19,27,34,37,40‐heptaoxahexa­cyclo[15.15.9.1^5,9.1^21,25.0^13,41.0^29,33]­tritetra­conta‐5(42),6,8,13(41),­14,16,21(43),22,24,29(33),30,32‐dodecaene, C₄₂H₅₀O₉, adopts the 1,3‐alternate conformation owing to the presence of a 1,3‐polyether chain.