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.

Antioxidant and antimicrobial properties of 2-(4,5-dihydro-1H-pyrazol-1-yl)-pyrimidine and 1-carboxamidino-1H-pyrazole derivatives

Five previously synthesized 4-trifluoromethyl-2-(5-aryl-3-styryl-1H-pyrazol-1yl)-pyrimidines and six 5-aryl-3-styryl-1-carboxamidino-1H-pyrazole derivatives were screened for their antioxidant proprieties. The antioxidant activities were evaluated by using the DPPH and the HRP/luminol/H2O2 chemiluminescence assay systems and for their antimicrobial activity (MIC). The results were good for those series in some concentration in comparison with the standards.

2,2,6-Trimethyl-5-[2-(4-methylphenyl)ethynyl]-4H-1,3-dioxin-4-one

The 1,3-dioxin-4-one ring in the title compound, C(16)H(16)O(3), is in a half-boat conformation with the quaternary O-C(CH(3))(2)-O atom lying 0.546 (1) angstrom out of the plane defined by the remaining five atoms. The crystal structure is consolidated by C-H center dot center dot center dot O contacts that lead to supramolecular layers.

5-Methyl-2,4-bis(methylsulfanyl)tricyclo[6.2.1.0(2,7)]undeca-4,9-diene-3,6-dione

The structure analysis of the title compound, C(14)H(16)O(2)S(2), shows the SMe and H atoms of the bond linking the six-membered rings to be syn and also to be syn to the bridgehead -CH(2)- group. Each of the five-membered rings adopts an envelope conformation at the bridgehead -CH(2)- group. The dione-substituted ring adopts a folded conformation about the 1,4-C center dot center dot center dot C vector, with the ketone groups lying to one side. The cyclohexene ring adopts a boat conformation.

2-(4-Methylphenyl)-1H-anthraceno-[1,2-d]imidazole-6,11-dione: a fluorescent chemosensor

In the title compound, C(22)H(14)N(2)O(2), the five rings of the molecule are not coplanar. There is a significant twist between the four fused rings, which have a slightly arched conformation, and the pendant aromatic ring, as seen in the dihedral angle of 13.16 (8)degrees between the anthraquinonic ring system and the pendant aromatic ring plane.

Lead(II)-induced formation and coordination of 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one

Cyclization of (n)butyl glyoxylate thiosemicarbazone (HBuTSC) under reflux in the presence of Pb(OAc)(2) led to tile formation of the complex [Pb(HTz)(2)] (H(2)Tz = 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one), which after recrystallization from DMSO afforded the polymer [Pb(Tz)](n), the first example of a Tz(2-) metal complex. (C) 2008 Elsevier B.V. All rights reserved.

New insights on surface-enhanced Raman scattering based on controlled aggregation and spectroscopic studies, DFT calculations and symmetry analysis for 3,6-bi-2-pyridyl-1,2,4,5-tetrazine adsorbed onto citrate-stabilized gold nanoparticles

Asystematic study on the surface-enhanced Raman scattering (SERS) for 3,6-bi-2-pyridyl-1,2,4,5-tetrazine (bptz) adsorbed onto citrate-modified gold nanoparticles (cit-AuNps) was carried out based on electronic and vibrational spectroscopy and density functional methods. The citrate/bptz exchange was carefully controlled by the stepwise addition of bptz to the cit-AuNps, inducing flocculation and leading to the rise of a characteristic plasmon coupling band in the visible region. Such stepwise procedure led to a uniform decrease of the citrate SERS signals and to the rise of characteristic peaks of bptz, consistent with surface binding via the N heterocyclic atoms. In contrast, single addition of a large amount of bptz promoted complete aggregation of the nanoparticles, leading to a strong enhancement of the SERS signals. In this case, from the distinct Raman profiles involved, the formation of a new SERS environment became apparent, conjugating the influence of the local hot spots and charge-transfer (CT) effects. The most strongly enhanced vibrations belong to a(1) and b(2) representations, and were interpreted in terms of the electromagnetic and the CT mechanisms: the latter involving significant contribution of vibronic coupling in the system. Copyright (C) 2010 John Wiley & Sons, Ltd.

2-(4-Methoxyphenylsulfinyl)cyclohexan-1-one

The cyclohexanone ring in the title compound, C(13)H(16)O(3)S, is in a distorted chair conformation. The intramolecular S center dot center dot center dot O(carbonyl) distance is 2.814 (2) angstrom. Molecules are connected into a two-dimensional array via C-H center dot center dot center dot O contacts involving the carbonyl and sulfinyl O atoms.

trans-[Ru(NO)(NH(3))(4)(py)](BF(4))(3)center dot H(2)O encapsulated in PLGA microparticles for delivery of nitric oxide to B16-F10 cells: Cytotoxicity and phototoxicity

The NO donor trans-[Ru(NO)(NH(3))(4)(py)](BF(4))(3).H(2)O (py = pyridine) was loaded into poly-lactic-co-glycolic acid (PLGA) microparticles using the double emulsification technique. Scanning electron microscopy (SEM) and dynamic light scattering revealed that the particles are spherical in shape, have a diameter of 1600 nm, and have low tendency to aggregate. The entrapment efficiency was 25%. SEM analysis of the melanoma cell B16-F10 in the presence of the microparticles containing the complex trans-[Ru(NO)(NH(3))(4)(py)](BF(4))(3).H(2)O (pyMP) showed that the microparticles were adhered to the cell surface after 2 h of incubation. The complex with concentrations lower than 1 x 10(-4) M did not show toxicity in B16-F 10 murine cells. The complex in solution is toxic at higher concentrations (> 1 x 10(-3) M), with cell death attributed to NO release following the reduction of the complex. pyMP is not cytotoxic due to the lower bioavailability and availability of the entrapped complex to the medium and its reducing agents. However, pyMP is phototoxic upon light irradiation. The phototoxicity strongly suggests that cell death is due to NO release from trans-[Ru(NO)(NH(3))(4)(py)](3+). This work shows that pyMP can serve as a model for a drug delivery system carrying the NO donor trans-[Ru(NO)(NH(3))(4)(py)](BF(4))(3).H(2)O, which can release NO locally at the tumor cell by radiation with light only. (c) 2007 Elsevier Inc. All rights reserved.

Mechanisms underlying the vasorelaxant action of the pimarane ent-8(14),15-pimaradien-3 beta-ol in the isolated rat aorta

Pimarane-type diterpenes were described to exert antispasmodic and relaxant activities. Based on this observation we hypothesized that the diterpene ent-8(14),15-pimaradien-3 beta-ol (PA-3 beta-ol) induced vascular relaxation. With this purpose, the present work investigates the mechanisms involved in the vasorelaxant effect of the pimarane-type diterpene PA-3 beta-ol. Vascular reactivity experiments, using standard muscle bath procedures, were performed in isolated aortic rings from male Wistar rats. Cytosolic calcium concentration ([Ca(2+)]c) was measured by confocal microscopy using the fluorescent probe Fluo-3AM. PA-3 beta-ol (10, 50 and 100 mu mol/l) inhibited phenylephrine and KCl-induced contraction in either endothelium-intact or denuded rat aortic rings. PA-3 beta-ol also reduced CaCl(2)-induced contraction in Ca(2+)-free solution containing KCl (30 mmol/l) or phenylephrine (0.1 mu mol/l). PA-3 beta-ol (1-300 mu mol/l) concentration dependently relaxed phenylephrine-pre-contracted rings with intact or denuded endothelium. The diterpene also relaxed KCl-pre-contracted rings with intact or denuded endothelium. Moreover, Ca(2+) mobilization study showed that PA-3 beta-ol (100 mu mol/l) and verapamil (1 mu mol/l) inhibited the increase in Ca(2+)-concentration in smooth muscle and endothelial cells induced by phenylephrine (10 mu mol/l) or KCl (60 mmol/l). Pre-incubation of intact or denuded aortic rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mu mol/l) and 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ 1 mu mol/l) produced a rightward displacement of the PA-3 beta-ol concentration-response curves. On the other hand, 7-nitroindazole (100 mu mol/l), 1400 W (1 mu mol/l), indomethacin (10 mu mol/l) and tetraethylammonium (1 mmol/l) did not affect PA-3 beta-ol-induced relaxation. Collectively, our results provide evidence that the effects elicited by PA-3 beta-ol involve extracellular Ca(2+) influx blockade. Its effects are also partly mediated by the activation of NO-cGMP pathway. (C) 2009 Elsevier B.V. All rights reserved.

Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR

Aneas I, Rodrigues MV, Pauletti BA, Silva GJ, Carmona R, Cardoso L, Kwitek AE, Jacob HJ, Soler JM, Krieger JE. Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR. Physiol Genomics 37: 52-57, 2009. First published January 6, 2009; doi: 10.1152/physiolgenomics.90299.2008. - To dissect the genetic architecture controlling blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four previously mapped BP quantitative trait loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway rat (BN) averaging 13 - 29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12 or 13 generations. Under normal salt intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect. On high salt intake (1% NaCl in drinking water for 2 wk), the chromosome 16 QTL had a marked impact on SBP, as did the QTLs on chromosome 2a and 2c (18, 17, and 19 mmHg, respectively), but not the QTL on chromosome 4. Thus these four QTLs affected BP phenotypes differently: 1) in the presence of high salt intake (chromosome 16), 2) only associated with normal salt intake (chromosome 4), and 3) regardless of salt intake (chromosome 2c and 2a). Moreover, salt sensitivity was abrogated in congenics SHR. BN2a and SHR. BN16. Finally, we provide evidence for the influence of genetic background on the expression of the mapped QTLs individually or as a group. Collectively, these data reveal previously unsuspected nuances of the physiological roles of each of the four mapped BP QTLs in the SHR under basal and/or salt loading conditions unforeseen by the analysis of the F2 cross.

Reduction of ICAM-1 expression by carbon monoxide via soluble guanylate cyclase activation accounts for modulation of neutrophil migration

Previously, it was demonstrated that the heme/heme oxygenase (HO)/carbon monoxide (CO) pathway inhibits neutrophil recruitment during the inflammatory response. Herein, we addressed whether the inhibitory effect of the HO pathway on neutrophil adhesion and migration involves the reduction of intracellular adhesion molecule type (ICAM)-1 and beta(2)-integrin expression. Mice pretreated with a specific inhibitor of inducible HO (HO-1), zinc protoporphyrin (ZnPP) IX, exhibit enhanced neutrophil adhesion and migration induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). These findings are associated with an increase in ICAM-1 expression on mesentery venular endothelium. In accordance, HO-1 inhibition did not enhance LPS-induced neutrophil migration and adhesion in ICAM-1-deficient mice. Furthermore, the treatment with a CO donor (dimanganese decacarbonyl, DMDC) that inhibits adhesion and migration of the neutrophils, reduced LPS-induced ICAM-1 expression. Moreover, neither DMDC nor ZnPP IX treatments changed LPS-induced beta(2)-integrin expression on neutrophils. The effect of CO on ICAM-1 expression seems to be dependent on soluble guanylate cyclase (sGC) activation, since 1H-(1,2,4)oxadiazolo (4,3-a)quinoxalin-1-one (sGC inhibitor) prevented the observed CO effects. Finally, it was observed that the nitric oxide (NO) anti-inflammatory effects on ICAM-1 expression appear to be indirectly mediated by HO-1 activation, since the inhibition of HO-1 prevented the inhibitory effect of the NO donor (S-nitroso-N-acetylpenicillamine) on LPS-induced ICAM-1 expression. Taken together, these results suggest that CO inhibits ICAM-1 expression on endothelium by a mechanism dependent on sGC activation. Thus, our findings identify the HO-1/CO/guanosine 3`5`-cyclic monophosphate pathway as a potential target for the development of novel pharmacotherapy to control neutrophil migration in inflammatory diseases.

Synthesis, characterization, X-ray structure and in vitro anti mycobacterial and antitumoral activities of Ru(II) phosphine/diimine complexes containing the ""SpymMe(2)"" ligand, SpymMe(2)=4,6-dimethyl-2-mercaptopyrimidine

The reaction of cis-[RuCl2(dppb)(N-N)], dppb = 1,4-bis(diphenylphosphino)butane, complexes with the ligand HSpymMe(2), 4,6-dimethyl-2-mercaptopyrimidine, yielded the cationic complexes [Ru(SpymMe(2))(dppb)(N-N)]PF6, N-N = bipy (1) and Me-bipy (2), bipy = 2,2`-bipyridine and Me-bipy = 4,4`dimethyl-2,2`-bipyridine, which were characterized by spectroscopic and electrochemical techniques and X-ray crystallography and elemental analysis. Additionally, preliminary in vitro tests for antimycobacterial activity against Mycobacterium tuberculosis H37Rv ATCC 27264 and antitumor activity against the MDA-MB-231 human breast tumor cell line were carried out on the new complexes and also on the precursors cis-[RuCl2(dppb)(N-N)], N-N = bipy (3) and Me-bipy (4) and the free ligands dppb, bipy, Me-bipy and SpymMe(2). The minimal inhibitory concentration (MIC) of compounds needed to kill 90% of mycobacterial cells and the IC50 values for the antitumor activity were determined. Compounds 1-4 exhibited good in vitro activity against M. tuberculosis, with MIC values ranging between 0.78 and 6.25 mu g/mL, compared to the free ligands (MIC of 25 to >50 mu g/mL) and the drugs used to treat tuberculosis. Complexes I and 2 also showed promising antitumor activity, with IC50 values of 0.46 +/- 0.02 and 0.43 +/- 0.08 mu M, respectively, against MDA-MB-231 breast tumor cells. (C) 2008 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.

Spectroscopic and theoretical studies of some N-methoxy-N-methyl-2-[(4 `-substituted) phenylsulfonyl]propanamides

The analysis of the IR carbonyl band of the N-methoxy-N-methyl-2-[(4`-substituted)phenyisulfonyI]propanamides Y-PhSO(2)CH(Me)C(O)N(OMe)Me (Y = OMe 1, Me 2, H 3, Cl 4, NO(2) 5), supported by HF/6-31G(d,p) calculations of 3,, indicated the existence of two gauche conformers (g(1) and g(2)), the g, conformer being the most stable and the least polar one (in gas phase and in solution). Both conformers are present in solution of the non polar solvent (CCl(4)) for 1-5 and in solution of the more polar solvents (CHCl(3)) for 1. 4, 5 and (CH(2)Cl(2)) for 5, while only the g(1) conformer is present in solution of the most polar solvent (CH(3)CN) for 1-5. The g, and g2 conformers correspond to the enantiomeric pairs of diastereomers (diast(1) and diast(2)) whose relative configurations are [C(3)(R)N(R)]/[C(3)(s)N(s)] and [C(3)(R)N(s)]/[C(3)(s)N(R)], respectively. The computed carbonyl frequencies for g(1) (diast(1)) and g(2) (diast(2)) stereoisomers of3 match well the experimental values. The NBO analysis, for 3 shows the important role of the orbital interactions in conformer stabilization and the overall balance of these interactions corroborates that the g, conformer is more stable than the 92 one. The observed abnormal solvent effect on the relative intensities of the carbonyl doublet components is attributed to the molecular crowding in the g2 conformer which hinders its solvation in comparison to the g, conformer (diast(1)). X-ray single crystal analysis performed for 3 shows the existence Of two 92, and g(1b) conformers of diastereomers (diast2, and diast(1b)) whose absolute configurations are [C(3)(R)N(s)] and [C(3)(R)N(R)], respectively. The larger population and. thus, the larger stabilization of the g(2), conformer over the gib form in the crystals may be associated with a larger energy gain deriving from dipole moment coupling in the former conformer along with a series of C-H center dot center dot center dot O electrostatic and hydrogen bond interactions, (C) 2009 Elsevier B.V. All rights reserved.