2-(4,5,6,7-tetrafluorobenzimidazol-2-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, a hydrogen-bonded organic quasi-1D ferromagnet

The title radical (F4BlmNN) is a stable nitronylnitroxide that forms hydrogen-bonded NH center dot center dot center dot ON chains in the solid state. The chains assemble the F4BlmNN molecules to form stacked contacts between the radical groups, in a geometry that is expected to exhibit ferromagnetic (FM) exchange based on spin polarization (SP) models. The experimental magnetic susceptibility of F4BlmNN confirms the expectation, showing 1-D Heisenberg chain FM exchange behavior over 1.8-300 K with an intrachain exchange constant Of J(chain)/k = +22 K. At lower temperatures, ac magnetic susceptibility and variable field heat capacity measurements show that F4BlmNN acts as a quasi-1-D ferromagnet. The dominant ferromagnetic exchange interaction is attributable to overlap between spin orbitals of molecules within the hydrogen-bonded chains, consistent with the SP model expectations. The chains appear to be antiferromagnetically exchange coupled, giving cusps in the ac susceptibility and zero field heat capacity at lower temperatures. The results indicate that the sample orders magnetically at about 0.7 K. The magnetic heat capacity ordering cusp shifts to lower temperatures as external magnetic field increases, consistent with forming a bulk antiferromagnetic phase below a Neel temperature of T-N(0) = 0.72 K, with a critical field of H-c approximate to 1800 Oe. The interchain exchange is estimated to be zJ/k congruent to (-)0.1 K.

Molecular conformation of the racemic indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide

This paper presents the structural characterization of the indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide, which was unambiguously determined by X-ray diffraction (XRD) to be a racemate (R/S: 50/50) crystallizing in an achiral crystal structure (P2(1)/c, a = 9.3180(1) , b = 7.9070(2) , c = 19.7550(4) , beta = 103.250(1)A degrees, V = 1416.75(5) (3) and Z = 4). The diastereomers are related by the inversion symmetry and linked by H bond forming a dimer. The crystal packing is stabilized by hydrogen bonds, including the classical one responsible for the formation of centrosymmetric dimers, and non-classical ones involving C-H center dot center dot center dot O and C-H center dot center dot center dot pi-aryl interactions. The intra and intermolecular geometry of the title compound is compared to the (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxylic acid one, which also present an achiral crystal structure from racemates (R/S: 50/50). The two indan derivatives crystallize in a very similar unit cell.

Vibrational properties, crystal X-ray diffraction structure and quantum chemical calculations on a divalent sulfur substituted phthalimide: 1H-Isoindole-1,3(2H)-dione, 2-[(methoxycarbonyl)thio]

Structural and conformational properties of 1H-Isoindole-1,3(2H)-dione, 2-[(methoxycarbonyl)thio] (S-phthalimido O-methyl thiocarbonate) are analyzed using a combined approach including X-ray diffraction, vibrational spectra and theoretical calculation methods. The vibrational properties have been studied by infrared and Raman spectroscopies along with quantum chemical calculations (B3LYP and B3PW91 functional in connection with the 6-311++G** and aug-cc-pVDZ basis sets). The crystal structure was determined by X-ray diffraction methods. The substance crystallizes in the monoclinic P2(1)/c space group with a = 6.795(1), b = 5.109(1), c = 30.011(3) angstrom, beta = 90.310(3)degrees and Z = 4 molecules per unit cell. The conformation adopted by the N-S-C=O group is syn (C=O double bond in synperiplanar orientation with respect to the N-S single bond). The experimental molecular structure is well reproduced by the MP2/aug-cc-pVDZ method. (C) 2010 Elsevier B.V. All rights reserved.

Ultrasound promoted greener synthesis of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles

A rapid and cleaner procedure for the synthesis of a series of 2-(3,5-diaryl-45-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles under ultrasonic irradiation in ethanol is described. (C) 2010 Elsevier B.V. All rights reserved.

ATP pulse and calcium homeostasis in cells from hepatopancreas of Dilocarcinus pagei, a freshwater crab

Calcium (Ca) is critical for crustaceans due to their molting cycle and its presence in the carapace as calcium carbonate, apart from the usual functions of Ca, such as cell signalling. Ca transport in Dilocarcinus pagei, a freshwater crab, was studied in isolated cells from hepatopancreas to further characterize Ca transport mechanisms in these crabs. Cells were isolated and loaded with Fluo-3, a calcium fluorescent dye. Three different cell treatments were performed: Group 1 cells were Ca free during cell dissociation, and calcium was present (at 1mM) for fluorescence cell loading and transport experiments (FC); Group 2 cells were calcium free during cell dissociation and for transport experiments, but not during cell loading (LC); and Group 3 cells were Ca free during cell dissociation, cell loading and transport experiments (WC). Intracellular Ca was recorded through time after ATP was added to the cells and ATP caused an increase in Ca efflux within 30s in all cells. WC cells showed the smallest Ca efflux compared to the other cells, probably because it was intracellularly Ca ""depleted"". Vanadate and amiloride decreased the Ca efflux when ATP was added to the cells, while verapamil did not cause any effect in Ca efflux, confirming the presence of a Ca(2+)-ATPase sensitive to vanadate in hepatopancreas of D. pagei. In a different set of experiments, cells were also exposed to a Ca pulse of 1 and 10mM during 180s. 10mM Ca increased intracellular Ca compared to 1mM, and the increase was not recovered during the experimental time. Additionally, Ca influx was reduced by verapamil and amiloride, but not completely. The results suggest that Ca influx probably occurs through an undefined exchanger, apart from Ca channels (verapamil sensitive) and electrogenic 1Na(+)(1H(+))/1 Ca(2+) exchanger (amiloride-sensitive). Similarities between freshwater and seawater crabs, lobsters and crayfish in relation to plasma membrane Ca transporters, although the environment where they live is quite diverse, suggest that universal mechanisms for Ca homeostasis are widespread among crustaceans. (C) 2010 Elsevier Inc. All rights reserved.

Modulation of rat neutrophil function in vitro by cis- and trans-MUFA

In the present study, the effects of trans-MUFA, elaidic acid (EA; 18 : 1-9t) and vaccenic acid (VA; 18 : 1-11t) on rat neutrophil functions were compared with those of cis-monounsaturated oleic acid (OA) (18 : 1-9c) and saturated stearic acid (SA; 18 : 0) (10-150 mu M). Trans-fatty acids enhanced neutrophil phagocytic capacity, superoxide (O(2)(center dot-)) and hydrogen peroxide production, and candidacidal activity. The same effects were observed for OA. Cells treated with trans-MUFA showed reduced production of NO(center dot), whereas those treated with OA showed an increase in production. Treatment with SA did not provoke significant effect on the parameters investigated. The increase in O(2)(center dot-) production induced by MUFA was not observed when diphenyleneiodonium, an NADPH oxidase inhibitor, was added to the medium. This finding suggests that MUFA stimulate neutrophil NADPH oxidase activity. The addition of 3-[1-[3-(dimethylamino)propyl]-1H-indol-3-yl]-4-(1H-inclol-3-yl)-1H-pyrrole-2,5-dione, a protein kinase C (PKC) inhibitor, and wortmannin, a phosphatidylinositol-3 kinase (PI3K) inhibitor, did not affect O(2)(center dot-) production induced by MUFA. Therefore, the mechanisms by which MUFA stimulate NADPH oxidase are not dependent on PKC and do not seem to involve PI3K. Experiments using Zn(2+), an inhibitor of NADPH oxidase H(+) channel, indicated that MUFA activate the NADPH oxidase complex in rat neutrophil due to opening of H(+) channel.

Prolonged exposure to palmitate impairs fatty acid oxidation despite activation of AMP-activated protein kinase in skeletal muscle cells

The aim of this study was to investigate the chronic effects of palmitate on fatty acid (FA) oxidation, AMPK/ACC phosphorylation/activation, intracellular lipid accumulation, and the molecular Mechanisms involved in these processes in skeletal muscle cells. Exposure of L6 myotubes for 8 h to 200, 400, 600, and 800 mu M of palmitate did rot affect cel viability but significantly reduced FA oxidation by similar to 26.5%, similar to 43.5%, similar to 50%, and similar to 47%, respectively. Interestingly, this occurred despite significant increases in AMPK (similar to 2.5-fold) and ACC (similar to 3-fold) phosphorylation and in malonyl-CoA decarboxylase activity (similar to 38-60%). Low concentrations of palmitate (50-100 mu M) caused an increase (similar to 30%) in CPT-I activity. However, as the concentration of palmitate increased, CPT-I activity decreased by similar to 32% after exposure for 8 h to 800 mu M of palmitate. Although FA uptake was reduced (similar to 35%) in cells exposed to increasing, palmitate concentrations, intracellular lipid accumulation increased in a dose-dependent manner, reaching values similar to 2.3-, similar to 3-, and 4-fold higher than control in muscle cells exposed to 400, 600, and 800 mu M palmitate, respectively. Interestingly, myotubes exposed to 400 mu M of palmitate for 1h increased basal glucose uptake and glycogen synthesis by similar to 40%. However, as time of incubation in the presence of palmitate progressed from 1 to 8h, these increases were abolished and a time-dependent inhibition of insulin-stimulated glucose uptake (similar to 65%) and glycogen synthesis (30%) was observed in myotubes. These findings may help explain the dysfunctional adaptations that occur in glucose and FA Metabolism in skeletal muscle under conditions of chronically elevated circulating levels of non-esterified FAs. Such as in obesity and Type 2 Diabetes.

Role of a Novel Tetrodotoxin-Resistant Sodium Channel in the Nitrergic Relaxation of Corpus Cavernosum from the South American Rattlesnake Crotalus Durissus Terrificus

Introduction. Coitus in snakes may last up to 28 hours; however, the mechanisms involved are unknown. Aim. To evaluate the relevance of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) system in snake corpus cavernosum reactivity. Methods. Hemipenes were removed from anesthetized South American rattlesnakes (Crotalus durissus terrificus) and studied by light and scanning electronic microscopy. Isolated Crotalus corpora cavernosa (CCC) were dissected from the non-spiny region of the hemipenises, and tissue reactivity was assessed in organ baths. Main Outcome Measures. Cumulative concentration-response curves were constructed for acetylcholine (ACh), sodium nitroprusside (SNP), 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272), and tadalafil in CCC precontracted with phenylephrine. Relaxation induced by electrical field stimulation (EFS) was also done in the absence and presence of N omega nitro-L-arginine methyl ester (L-NAME; 100 mu M), 1H-[1, 2, 4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 mu M) and tetrodotoxin (TTX; 1 mu M). Results. The hemipenes consisted of two functionally concentric corpora cavernosa, one of them containing radiating bundles of smooth muscle fibers (confirmed by alpha-actin immunostaining). Endothelial and neural nitric oxide synthases were present in the endothelium and neural structures, respectively; whereas soluble guanylate cyclase and PDE5 were expressed in trabecular smooth muscle. ACh and SNP relaxed isolated CCC, with the relaxations being markedly reduced by L-NAME and ODQ, respectively. BAY 41-2272 and tadalafil caused sustained relaxations with potency (pEC(50)) values of 5.84 +/- 0.17 and 5.10 +/- 0.08 (N = 3-4), respectively. In precontracted CCC, EFS caused frequency-dependent relaxations that lasted three times longer than those in mammalian CC. Although these relaxations were almost abolished by either L-NAME or ODQ, they were unaffected by TTX. In contrast, EFS-induced relaxations in marmoset CC were abolished by TTX. Conclusions. Rattlesnake CC relaxation is mediated by the NO-cGMP-PDE5 pathway in a manner similar to mammals. The novel TTX-resistant Na channel identified here may be responsible for the slow response of smooth muscle following nerve stimulation and could explain the extraordinary duration of snake coitus. Capel RO, Monica FZ, Porto M, Barillas S, Muscara MN, Teixeira SA, Arruda AMM, Pissinatti, L, Pissinatti A, Schenka AA, Antunes E, Nahoum C, Cogo JC, de Oliveira MA, and De Nucci G. Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus. J Sex Med 2011;8:1616-1625.

fac-/mer-[RuCl(3)(NO)(P-N)] (P-N = [o-(N,N-dimethylamino)phenyl]diphenylphosphine): Synthesis, characterization and DFT calculations

Complex fac-[RuCl(3)(NO)(P-N)] (1) was synthesized from the reaction of [RuCl(3)(H(2)O)(2)(NO)] and the P-N ligand, o-[(N,N-dimethylamino)phenyl]diphenylphosphine) in refluxing methanol solution, while complex mer,trans-[RuCl(3)(NO)(P-N)] (2) was obtained by photochemical isomerization of (1) in dichloromethane solution. The third possible isomer mer, cis-[RuCl(3)(NO)(P-N)] (3) was never observed in direct synthesis as well as in photo-or thermal-isomerization reactions. When refluxing a methanol solution of complex (2) a thermally induced isomerization occurs and complex (1) is regenerated. The complexes were characterized by NMR ((31)P{(1)H}, (15)N{1H} and 1H), cyclic voltammetry, FTIR, UV-Vis, elemental analysis and X-ray diffraction structure determination. The (31)P{(1)H} NMR revealed the presence of singlet at 35.6 for (1) and 28.3 ppm for (2). The (1)H NMR spectrum for (1) presented two singlets for the methyl hydrogens at 3.81 and 3.13 ppm, while for (2) was observed only one singlet at 3.29 ppm. FTIR Ru-NO stretching in KBr pellets or CH(2)Cl(2) solution presented 1866 and 1872 cm(-1) for (1) and 1841 and 1860 cm(-1) for (2). Electrochemical analysis revealed a irreversible reduction attributed to Ru(II)-NO(+) -> Ru(II)-NO(0) at -0.81 V and -0.62 V, for (1) and (2), respectively; the process Ru(II) -> Ru(III), as expected, is only observed around 2.0 V, for both complexes. Studies were conducted using (15)NO and both complexes were isolated with (15)N-enriched NO. Upon irradiation, the complex fac-[RuCl(3)(NO)(P-N)] (1) does not exchange (14)NO by (15)NO, while complex mer, trans-[RuCl(3)(NO)(P-N)] (2) does. Complex mer, trans-[RuCl(3)((15)NO)(P-N)] (2`) was obtained by direct reaction of mer, trans-[RuCl(3)(NO)(P-N)] (2) with (15)NO and the complex fac-[RuCl(3)((15)NO)(P-N)] (1`) was obtained by thermal-isomerization of mer, trans-[RuCl(3)((15)NO)(P-N)] (2`). DFT calculation on isomer energies, electronic spectra and electronic configuration were done. For complex (1) the HOMO orbital is essentially Ru (46.6%) and Cl (42.5%), for (2) Ru (57.4%) and Cl (39.0%) while LUMO orbital for (1) is based on NO (52.9%) and is less extent on Ru (38.4%), for (2) NO (58.2%) and Ru (31.5%). (C) 2011 Elsevier B. V. All rights reserved.

Synthesis and structural characterization of a new polymeric zinc(II) complex with thiophene-2-carboxylic acid

A new polymeric zinc(II) complex with thiophene-2-carboxylic acid (-tpc) of composition [Zn2(C20H12O8S4)]n was obtained and structurally characterized by X-ray diffraction, thermal analysis, nuclear magnetic resonance (NMR), and infrared spectroscopies. Upfield shift in the 1H-NMR spectrum is explained by the crystalline structure, which shows the thiophene rings overlapping each other in parallel pairs. The compound crystallizes in the monoclinic system, space group P21/c, with a = 9.7074(4) angstrom, b = 13.5227(3) angstrom, c = 18.9735(7) angstrom, = 95.797(10)degrees, and Z = 4. Three -tpc groups bridge between two Zn(II) ions through oxygens and the fourth one bridges between one of these ions and the third one, symmetry related by a twofold screw axis. This arrangement gives rise to infinite chains along the crystallographic a direction. The metal atoms display an approximate tetrahedral configuration. The complex is insoluble in water, ethanol, and acetone, but soluble in dimethyl sulfoxide.

Diphenyllead(IV) thiosemicarbazonates and pyrazolonates: Synthesis and characterization

Cyclization of thiosemicarbazones derived from beta-keto esters and beta-keto amides (HTSC) in the presence of diphenyllead(IV) acetate was explored in methanol solution at room temperature and under reflux. All beta-keto ester TSCs underwent cyclization to give the corresponding pyrazolone (HL), which, except in one case, deprotonated and coordinated the PbPh(2)(2+) moiety to form homoleptic [PbPh(2)(L)(2)] or heteroleptic [PbPh(2)(OAc)(L)] derivatives. Cyclization did not occur with beta-keto amide TSCs and only [Pbph(2)(TSC)(2)] or [PbPh(2)(OAc)(TSC)] thiosernicarbazonates were isolated. The complexes were characterized by IR spectroscopy in the solid state and by (1)H, (13)C and (207)Pb NMR spectroscopy in DMSO-d(G) solution, in which they evolve and decompose with time. Additionally, crystals of p-acetoacetanisidide thiosemicarbazone (HTSC(10)), [PbPh(2)(OAc)(L(5))] center dot MeOH (HL(5) = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazolone-1-carbothioamide), [PbPh(2)Cl(L(2))] (HL(2) = 2,5-dihydro-5-oxo-3-phenyl-1H-pyrazolone-1-carbothioamide), [PbPh(2)(OAc)(TSC(8))]center dot 2MeOH (HTSC(8) = acetoacetanilide thiosemicarbazone), [PbPh(2)(OAc)(TSC(10))]center dot H(2)O and [PbPh(2)(OAc)(TSC(11))] center dot 0.75MeOH (HTSO(11) = o-acetoacetotoluidide) were studied by X-ray crystallography. The complexes, monomers or dimers with almost linear C-Pb-C moieties, are compared with the corresponding derivatives of Pb(II). (C) 2009 Elsevier Ltd. All rights reserved.

Synthesis and characterization of a new mebendazole salt: Mebendazole hydrochloride

Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ.HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is stabilized by the presence of three N-H...Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ center dot HCI indicates that the compound is stable up to 160 degrees C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:542-552, 2008.

New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: Molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity

New Pd(II) and Pt(II) complexes [ML2] (HL = a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M = Pd, Pt) or Pd(OAc)(2) with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cis-platinum-resistant cell line A2780cisR. (c) 2007 Elsevier Inc. All rights reserved.

Evidence of a Ca(2+)-(center dot)NO-cGMP signaling pathway controlling zoospore biogenesis in the aquatic fungus Blastocladiella emersonii

The sporulation stage of the aquatic fungus Blastocladiella emersonii culminates with the formation and release to the medium of a number of zoospores, which are motile cells responsible for the dispersal of the fungus. The presence in the sporulation solution of 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclases, completely prevented biogenesis of the zoospores. In addition, this compound was able to significantly reduce cGMP levels, which increase drastically during late sporulation, suggesting the existence of a nitric oxide-dependent mechanism for cGMP synthesis. Furthermore, increased levels of nitric oxide-derived products were detected during sporulation by fluorescence assays using DAF-2 DA, whose signal was drastically reduced in the presence of the nitric oxide synthase inhibitor N omega-Nitro-L-arginine methyl ester (L-NAME). These results were confirmed by quantitative chemiluminescent determination of the intracellular levels of nitric oxide-derived products. A putative nitric oxide synthase (NOS) activity was detected throughout sporulation, and this enzyme activity decreased significantly when L-NAME and 1-[2-(Trifluoromethyl)phenyl]imidazole (TRIM) were added to the assays. NOS assays carried out in the presence of EGTA showed decreased enzyme activity, suggesting the involvement of calcium ions in enzyme activation. Additionally, expressed sequence tags (ESTs) encoding putative guanylyl cyclases and a cGMP-phosphodiesterase were found in B. emersonii EST database (http://blasto.iq.usp.br), and the mRNA levels of the corresponding genes were observed to increase during sporulation. Altogether, data presented here revealed the presence and expression of guanylyl cyclase and cGMP phosphodiesterase genes in B. emersonii and provided evidence of a Ca(2+)-(center dot)NO-cGMP signaling pathway playing a role in zoospore biogenesis. (C) 2009 Elsevier Inc. All rights reserved.

Computer-Assisted Approach to Structural Elucidation of Lignans

This paper reports an expert system (SISTEMAT) developed for structural determination of diverse chemical classes of natural products, including lignans, based mainly on 13C NMR and 1H NMR data of these compounds. The system is composed of five programs that analyze specific data of a lignan and shows a skeleton probability for the compound. At the end of analyses, the results are grouped, the global probability is computed, and the most probable skeleton is exhibited to the user. SISTEMAT was able to properly predict the skeletons of 80% of the 30 lignans tested, demonstrating its advantage during the structural elucidation course in a short period of time.