Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid

Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37ºC in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 µM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 ± 0.03 and 5.0 ± 1.0 µM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.

Self-assembly of cyclometallated Pd(II) compounds directed by C-H center dot center dot center dot pi interactions: A structural evidence for metalloaromaticity in a cyclopalladated ring

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

(-)-Kolavenic acid

In the two, almost identical, molecules in the asymmetric unit of the title compound [ systematic name: (E)-3-methyl-5-(1,2,4a, 5-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1yl) pent-2-enoic acid], C20H32O2, the rings are trans fused. The cyclohexane ring has a chair conformation and the cyclohexene ring a distorted half-boat conformation. The two independent molecules are connected into a dimer via O-H center dot center dot center dot O hydrogen bonds. The dimers are associated into supramolecular chains along c via C-H center dot center dot center dot O contacts.

THE CRYSTAL-STRUCTURE OF BENZOYL-HISTIDINE MONOHYDRATE

The crystal structure of benzoyl-histidine monohydrate (BYLH hereafter), C-13H-12N-3O-3. H2O was determined from three dimensional data of 3012 independent reflections measured on a Enraf-Nonius (CAD4) single crystal diffractometer. The compound crystallizes in the orthorhombic space group P2(1)2(1)2(1) with cell dimensions alpha = 7.102(1) angstrom, b = 13.783(3) angstrom, c = 14.160(4) angstrom, V = 1385.92 angstrom-3, F.W. = 277.28, F(000) = 584 Q(calc) = 1.32 g cm-3 and Z = 4.The structure was solved with direct methods. All positional and anisotropic thermal parameters were refined by full-matrix least-squares calculations. The final reliability factor was R = 0.040, while the weighted one was Rw = 0.034. The H atoms found in the difference Fourier map were refined isotropically.The compound consists of a histidine molecule bound to a benzoyl group. There is also a cocrystallized water molecule stabilized through a hydrogen bridge.The 5-membered ring of the histidine has its tautomeric form, after the transfer of the H atom from the N(delta) to the N(epsilon) atom of the ring. There is an sp2 conformation around C6 while the conformation around C3 is that of sp3. The histidine ring forms with the benzene ring a dihedral angle of 109.8(1)-degree.All angle values and bond distances agree very well with the expected values in the literature.

Moonlets wandering on a leash-ring

Since the Voyager flybys, embedded moonlets have been proposed to explain some of the surprising structures observed in Saturn's narrow F ring. Experiments conducted with the Cassini spacecraft support this suggestion. Images of the F ring show bright compact spots, and seven occultations of stars by the F ring, monitored by ultraviolet and infrared experiments, revealed nine events of high optical depth. These results point to a large number of such objects, but it is not clear whether they are solid moonlets or rather loose particle aggregates. Subsequent images suggested an irregular motion of these objects so that a determination of their orbits consistent with the F ring failed. Some of these features seem to cross the whole ring. Here we show that these observations are explained by chaos in the F ring driven mainly by the 'shepherd' moons Prometheus and Pandora. It is characterized by a rather short Lyapunov time of about a few hundred orbital periods. Despite this chaotic diffusion, more than 93 per cent of the F-ring bodies remain confined within the F ring because of the shepherding, but also because of a weak radial mobility contrasted by an effective longitudinal diffusion. This chaotic stirring of all bodies involved prevents the formation of 'propellers' typical of moonlets, but their frequent ring crossings explain the multiple radial 'streaks' seen in the F ring. The related 'thermal' motion causes more frequent collisions between all bodies which steadily replenish F-ring dust and allow for ongoing fragmentation and re-accretion processes (ring recycling).

Some comments on the F ring-Prometheus-Pandora environment

The system formed by the F ring and two close satellites, Prometheus and Pandora, has been analysed since the time that Voyager visited the planet Saturn. During the ring plane crossing in 1995 the satellites were found in different positions as predicted by the Voyager data. Besides the mutual effects of Prometheus and Pandora, they are also disturbed by a massive F ring. Showalter et al. [Icarus 100 (1992) 394] proposed that, the core of the ring has a mass which corresponds to a moonlet varying in size from 15 to 70 kin in radius which can prevent the ring from spreading due to dissipative forces, such as Poynting-Robertson drag and collisions. We have divided this work into two parts. Firstly we analysed the secular interactions between Prometheus-Pandora and a massive F ring using the secular theory. Our results show the variation in eccentricity and inclination of the satellites and the F ring taking into account a massive ring corresponding to a moonlet of different sizes. There is also a population of dust particles in the ring in the company of moonlets at different sizes [Icarus 109 (1997) 304]. We also analysed the behaviour of these particles under the effects of the Poynting-Robertson drag and radiation pressure. Our results show that the time scale proposed for a dust particle to leave the ring is much shorter than predicted before even in the presence of a coorbital moonlet. This result does not agree with the confinement model proposed by Dermott et al. [Nature 284 (1980) 309]. In 2004, Cassini mission will perform repeated observations of the whole system, including observations of the satellites and the F ring environment. These data will help us to better understand this system. (C) 2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

A new shadow-ring device for measuring diffuse solar radiation at the surface

A new shadow-ring device for measuring diffuse solar radiation at the surface is presented. In this device the seasonal variation of shadow is followed by moving the detector horizontally. This unique characteristic facilitates its application for long and continuous periods of time. The blocking effect caused by the ring and other related geometric properties are formulated considering the diffuse solar radiation isotropic. The correction factor, shadow size, and ring-detector distance are derived as a function of radius and width of the ring, sun position, and local latitude. The largest blocking occurs during summer, when the ring-detector distance and the shadow width are the smallest, and it is compensated by a smaller blocking effect in the winter period. The performance of the new device is verified comparing daily values of diffuse solar radiation measured simultaneously with a similar device from Kipp & Zonen, Inc. The results show a very good agreement (within 2.5%) between both devices. The new device was also able to reproduce the radiometric properties of the local atmosphere based on 3-yr-long measurements of direct solar radiation using a pyrheliometer. The new device can be applied to estimate daily values of diffuse solar radiation at the surface in the range of 30degreesN-30degreesS with results comparable to other similar apparatuses.

Novel allosteric conformation of human HB revealed by the hydration and anion effects on O-2 binding

The effect of anions on the stability of different functional conformations of Hb is examined through the determination of the dependence of O-2 affinity on water activity (a(w)). The control of a(w) is effected by varying the sucrose osmolal concentration in the bathing solution according to the osmotic stress method. Thus, the hydration change following Hb oxygenation is determined as a function of Cl- and of DPG concentration. We find that only similar to 25 additional water molecules bind to human Hb during the deoxy-to-oxy conformation transition in the absence of anions, in contrast with similar to 72 that bind in the presence of more than 50 mM Cl- or more than 15 mu M DPG. We demonstrate that the increase in the hydration change linked with oxygenation is coupled with anion binding to the deoxy-Hb. Hence, we propose that the deoxy-Hb coexists in two allosteric conformations which depend on whether anion is bound or not: the tense T-state, with low oxygen affinity and anion bound, or a new allosteric P-state, with intermediate oxygen affinity and free of bound anions. The intrinsic oxygen affinity of this unforeseen P-state and the differential binding of Cl-, DPG, and H2O between states P and T and P and R are characteristics which are consistent with those expected for a putative intermediate allosteric state of Hb. These findings represent a new opportunity to explore the structure-function relationships of hemoglobin regulation.

The strands of the F ring disturbed by its closest satellites

Some Voyager images showed that the F ring of Saturn is composed of at least four separate, non-intersecting, strands covering about 45 degrees in longitude. According to Murray et al. [Murray, C.D., Gordon, M., Giuliatti Winter, S.M. Unraveling the strands of Saturn's F ring. Icarus 129, 304, 1997.] this structure may be caused by undetected satellites embedded in the gaps.Due to precession, the satellites Prometheus and Pandora and the ring particles can experience periodic close encounters. Giuliatti Winter et al. [Giuliatti Winter, S.M, Murray, C.D., Gordon, M. Perturbations to Saturn's F-ring strands at their closest approach to Prometheus. Plan. Space Sciences, 48, 817, 2000.] analysed the behaviour of these four strands at closest approach with the satellite Prometheus. Their work suggests that Prometheus can induce the ring particles to scatter in the direction of the planet, thus increasing the population of small bodies in this region.In this work we analysed the effects of Prometheus on the radial structure of Saturn's F ring during the Voyager and early Cassini epochs. Our results show that at Voyager epoch Prometheus, and also Pandora, had a negligible influence in the strands. However, during the Cassini encounter Prometheus could affect the strands significantly, scattering particles of the inner strand in the direction of the planet. This process can contribute to the replenishment of material in the region between the F ring and the A ring, where two rings have recently been discovered [Porco, C. et al. Cassini imaging science. Initial results on Saturn's rings and small Satellites. Science, 307, 1226, 2005].We also analyse the behaviour of undetected satellites under the effects of these two satellites by computing the Lyapunov Characteristic Exponent. Our results show that these satellites have a chaotic behaviour which leads to a much more complex scenario. The new satellite S/2004 S6 also presents a chaotic behaviour with can alter the dynamic of the system, since this satellite crosses the orbit of the strands. (C) 2006 COSPAR. Published by Elsevier Ltd. All rights reserved.

Crystal and molecular structures of 4-substituted 3,4-dihydropyrimidin-2(1H)-ones studied by X-ray and AM1 and B3LYP calculations

(1) C13H13N3O5, Mr = 291.26, P (1) over bar, a = 7.4629(9), b = 7.9203(9), c = 12.126(2) angstrom, alpha = 86.804(5), beta = 78.471(7), gamma = 69.401(8)degrees, V = 657.3(2)angstrom(3), Z = 2, R-1 = 0.0454; (2) C11H12N2O4, Mr=236.23, Pbca, a=7.2713(9), b=14.234(1), c=20.848(3)angstrom, V= 2157.8(4) angstrom(3), Z=8, R-1=0.0504; (3) C13H13N2O3Cl, Mr = 280.70, P2/n, a = 17.344(2), b = 9.237(1), c = 18.398(2) angstrom; beta = 92.61(2)degrees, V = 2944.4(6) angstrom(3), Z = 8, R-1 = 0.0714. The conformational features of three 4-substituted-3-4-dihydropyrimidin-2(1H)-ones were investigated by computational and single crystal X-ray crystallographic studies. The geometries were optimized using semiempirical (AM1) and first principle calculations (B3LYP/6-31G**) methods, the rotational barriers for important functional groups were studied. In all structures the pyrimidinone rings are in a more or less distorted boat conformation. The phenyl and the furane rings are almost perpendicular to the best least-squares plane through the dihydropyrimidinone ring.

Periodic collisions between the moon Prometheus and Saturn's F ring

Saturn's F ring, which lies 3,400 km beyond the edge of the main ring system, was discovered by the Pioneer 11 spacecraft(1) in 1979. It is a narrow, eccentric ring which shows an unusual 'braided' appearance in several Voyager 1 images' obtained in 1980, although it appears more regular in images from Voyager 2 obtained nine months later(3). The discovery of the moons Pandora and Prometheus orbiting on either side of the ring provided a partial explanation for some of the observed features(4). Recent observations of Prometheus(5,6) by the Hubble Space Telescope show, surprisingly, that it is lagging behind its expected position by similar to 20 degrees. By modelling the dynamical evolution of the entire Prometheus-F ring-Pandora system, we show here that Prometheus probably encountered the core of the F ring in 1994 and that it may still be entering parts of the ring once per orbit. Collisions with objects in the F ring provide a plausible explanation for the observed lag and imply that the mass of the F ring is probably less than 25% that of Prometheus.

1,5-Diphenyl-4,8-bis(3-phenylpyrazol-1-yl)pyrazabole

The six-membered B(2)H(4) ring of the title compound, C(36)H(30)B(2)N(8), adopts a slightly distorted boat conformation, with the terminal B substituents in a trans orientation. One 3-phenylpyrazolyl group is in an equatorial position, whereas the second is in an axial position with respect to the plane defined by the B atoms.

Water regulation of actinomycin-D binding to DNA: the interplay among drug affinity, DNA long-range conformation, and hydration

Actiaomycin-D (actD) binds to natural DNA at two different classes of binding sites, weak and strong. The affinity for these sites is highly dependent on DNA se(sequence and solution conditions, and the interaction appears to be purely entropic driven Although the entropic character of this reaction has been attributed to the release of water molecules upon drug to DNA complex formation, the mechanism by which hydration regulates actD binding and discrimination between different classes of binding sites on natural DNA is still unknown. In this work, we investigate the role of hydration on this reaction using the osmotic stress method. We skew that the decrease of solution water activity, due to the addition of sucrose, glycerol ethylene glycol, and betaine, favors drug binding to the strong binding sites on DNA by increasing both the apparent binding affinity Delta G, and the number of DNA base pairs apparently occupied by the bound drug n(bp/actD). These binding parameters vary linearly with the logarithm of the molar fraction of water in solution log(X-w), which indicates the contribution of water binding to the energetic of the reaction. It is demonstrated that the hydration change measured upon binding increases proportionally to the apparent size of the binding site n(bp/uctD). This indicates that n(bp/actD) measured from the Scatchard plod is a measure of the size of the DNA molecule changing conformation due to ligand binding. We also find that the contribution of DNA deformation, gauged by n(bp/act) to the total free energy of binding Delta G, is given by Delta G = Delta G(local) + n(bp/actD) x delta G(DNA), where Delta G(local), = -8020 +/- 51 cal/mol of actD bound and delta G(DNa) = -24.1 +/- 1.7cal/mol of base pair at 25 degrees C. We interpret Delta G(local), as the energetic contribution due to the direct interactions of actD with the actual tetranucleotide binding site, and it n(bp/actB) X delta G(DNA) as that due to change inconformation, induced by binding, of it n(bp/actD) DNA base pairs flanking the local site. This interpretation is supported by the agreement found between the value of delta G(DNA) and the torsional free energy change measured independently. We conclude suggesting an allosteric model for ligand binding to DNA, such that the increase in binding affinity is achieved by increasing the relaxation of the unfavorable free energy of binding storage at the local site through a larger number of DNA base pairs. The new aspect on this model is that the size of the complex is not fixed but determined by solutions conditions, such as water activity, which modulate the energetic barrier to change helix conformation. These results may suggest that long-range allosteric transitions of duplex DNA are involved in the inhibition of RNA synthesis by actD, and more generally, in the regulation of transcription. (C) 2000 John Wiley & Sons, Inc.

THE FLUID SYSTEMS FOR THE SLD CHERENKOV RING IMAGING DETECTOR

We describe the design and operation of the fluid delivery, monitor and control systems for the SLD barrel Cherenkov Ring Imaging Detector (CRID). The systems deliver drift gas (C2H6+TMAE), radiator gas (C5F12+N2) and radiator liquid (C6F14). MeasUred critical quantities such as electron lifetime in the drift gas and ultra-violet (UV) transparencies of the radiator fluids, together with the operational experience, are also reported.

The brightening of Saturn's F ring

Image photometry reveals that the F ring is approximately twice as bright during the Cassini tour as it was during the Voyager flybys of 1980 and 1981. It is also three times as wide and has a higher integrated optical depth. We have performed photometric measurements of more than 4800 images of Saturn's F ring taken over a 5-year period with Cassini's Narrow Angle Camera. We show that the ring is not optically thin in many observing geometries and apply a photometric model based on single-scattering in the presence of shadowing and obscuration, deriving a mean effective optical depth tau approximate to 0.033. Stellar occultation data from Voyager PPS and Cassini VIMS validate both the optical depth and the width measurements. In contrast to this decades-scale change, the baseline properties of the F ring have not changed significantly from 2004 to 2009. However, we have investigated one major, bright feature that appeared in the ring in late 2006. This transient feature increased the ring's overall mean brightness by 84% and decayed with a half-life of 91 days. (c) 2012 Elsevier B.V. All rights reserved.