Axial binding of 2-methylimidazole to the tetraarylcarboxylatodiruthenium (II, III) core: X-ray crystal structure of [Ru-2(O2CC6H4-p-OMe)(4)(2-mimH)(2)](ClO4). 1.75CH(2)Cl(2).H2O

Diruthenium (II. III) complexes of the type [Ru-2(O2CAr)(4) (2-mimH)(2)](ClO4) (Ar = C6H4-p-X : X=OMe,1, X=Me, 2, 2-mimH=2-methylimidazole) have been isolated from the reaction of Ru2Cl(O2CAr)(4) with 2-mimH in CH2Cl2 followed by the addition of NaClO4. The crystal structure of 1.1.75CH(2)Cl(2).H2O has been determined. The crystal belongs to the monoclinic space group p2(1)/c with the following unit cell dimensions for the C40H40N4O16ClRu2.1.75CH(2)Cl(2).H2O (M = 1237.0) : a = 12.347(3)Angstrom, b = 17.615(5)Angstrom, c = 26.148(2)Angstrom,beta = 92.88(1)degrees. v = 5679(2)Angstrom(3). Z=4, D-c = 1.45 g cm(-3). lambda(Mo-K-alpha) = 0.7107 Angstrom, mu(Mo-K-alpha) = 8.1 cm(-1), T = 293 K, R = 0.0815 (wR(2) = 0.2118) for 5834 reflections with 1 > 2 sigma(I). The complex has a tetracarboxylatodiruthenium (II, III) core and two axially bound 2-methylimidazole ligands. The Ru-Ru bond length is 2.290(1)Angstrom. The Ru-Ru bond order is 2.5 and the complex is three-electron paramagnetic. The complex shows an irreversible Ru-2(II,III)-->Ru-2(Il,II) reduction near -0.2 V vs SCE in CH2Cl2-0. 1 MTBAP. The complexes exemplify the first adduct of the tetracarboxylatodiruthenium (II,III) core having N-donor ligands

Biochemical and structural characterization of residue 96 mutants of Plasmodium falciparum triosephosphate isomerase: active-site loop conformation, hydration and identification of a dimer-interface ligand-binding site

Plasmodium falciparum TIM (PfTIM) is unique in possessing a Phe residue at position 96 in place of the conserved Ser that is found in TIMs from the majority of other organisms. In order to probe the role of residue 96, three PfTIM mutants, F96S, F96H and F96W, have been biochemically and structurally characterized. The three mutants exhibited reduced catalytic efficiency and a decrease in substrate-binding affinity, with the most pronounced effects being observed for F96S and F96H. The k(cat) values and K-m values are (2.54 +/- 0.19) x 10(5) min(-1) and 0.39 +/- 0.049 mM, respectively, for the wild type; (3.72 +/- 0.28) x 10(3) min(-1) and 2.18 +/- 0.028 mM, respectively, for the F96S mutant;(1.11 +/- 0.03) x 10(4) min(-1) and 2.62 +/- 0.042 mM, respectively, for the F96H mutant; and (1.48 +/- 0.05) x 10(5) min(-1) and 1.20 +/- 0.056 mM, respectively, for the F96W mutant. Unliganded and 3-phosphoglycerate (3PG) complexed structures are reported for the wild-type enzyme and the mutants. The ligand binds to the active sites of the wild-type enzyme (wtPfTIM) and the F96W mutant, with a loop-open state in the former and both open and closed states in the latter. In contrast, no density for the ligand could be detected at the active sites of the F96S and F96H mutants under identical conditions. The decrease in ligand affinity could be a consequence of differences in the water network connecting residue 96 to Ser73 in the vicinity of the active site. Soaking of crystals of wtPfTIM and the F96S and F96H mutants resulted in the binding of 3PG at a dimer-interface site. In addition, loop closure at the liganded active site was observed for wtPfTIM. The dimer-interface site in PfTIM shows strong electrostatic anchoring of the phosphate group involving the Arg98 and Lys112 residues of PfTIM.

Recognition of active and inactive catalytic triads: A template based approach

It Is well established that a sequence template along with the database is a powerful tool for identifying the biological function of proteins. Here, we describe a method for predicting the catalytic nature of certain proteins among the several protein structures deposited in the Protein Data Bank (PDB) For the present study, we considered a catalytic triad template (Ser-His-Asp) found in serine proteases We found that a geometrically optimized active site template can be used as a highly selective tool for differentiating an active protein among several inactive proteins, based on their Ser-His-Asp interactions. For any protein to be proteolytic in nature, the bond angle between Ser O-gamma-Ser H-gamma His N-epsilon 2 in the catalytic triad needs to be between 115 degrees and 140 degrees The hydrogen bond distance between Ser H-gamma His N-epsilon 2 is more flexible in nature and it varies from 2 0 angstrom to 27 angstrom while in the case of His H-delta 1 Asp O-delta 1, it is from 1.6 angstrom to 2.0 angstrom In terms of solvent accessibility, most of the active proteins lie in the range of 10-16 angstrom(2), which enables easy accessibility to the substrate These observations hold good for most catalytic triads and they can be employed to predict proteolytic nature of these catalytic triads (C) 2010 Elsevier B V All rights reserved.

Biosorption of iron(III) from aqueous solutions using the husk of Cicer arientinum

Iron is a major pollutant released as a by-product during several industrial operations especially during acid mining of metal ores. In this paper, the use of Bengal gram husk (husk of channa dal, Cicer arientinum) in the biosorption of Fe(III) from aqueous solutions is discussed. Parameters like agitation time, adsorbent dosage and pH were studied at different Fe(Ill) concentrations. The adsorption data fit well with Langmuir and Freundlich isotherm models. The adsorption capacity (q(max)) calculated from the Langmuir isotherm was 72.16 mg of Fe(III)/g of the biosorbent at an initial pH of 2.5. Desorption Studies were performed at different concentrations of hydrochloric acid showing that quantitative recovery of the metal ion is possible. The infrared spectra of the biomass before and after treatment with Fe(III), revealed that hydroxyl, carboxyl and amide bonds are involved in the uptake of Fe(III) ions.

Active and break spells of the Indian summer monsoon

In this paper, we suggest criteria for the identification of active and break events of the Indian summer monsoon on the basis of recently derived high resolution daily gridded rainfall dataset over India (1951-2007). Active and break events are defined as periods during the peak monsoon months of July and August, in which the normalized anomaly of the rainfall over a critical area, called the monsoon core zone exceeds 1 or is less than -1.0 respectively, provided the criterion is satisfied for at least three consecutive days. We elucidate the major features of these events. We consider very briefly the relationship of the intraseasonal fluctuations between these events and the interannual variation of the summer monsoon rainfall. We find that breaks tend to have a longer life-span than active spells.While, almost 80% of the active spells lasted 3-4 days, only 40% of the break spells were of such short duration. A small fraction (9%) of active spells and 32% of break spells lasted for a week or longer. While active events occurred almost every year, not a single break occurred in 26% of the years considered. On an average, there are 7 days of active and break events from July through August. There are no significant trends in either the days of active or break events. We have shown that there is a major difference between weak spells and long intense breaks. While weak spells are characterized by weak moist convective regimes, long intense break events have a heat trough type circulation which is similar to the circulation over the Indian subcontinent before the onset of the monsoon. The space-time evolution of the rainfall composite patterns suggests that the revival from breaks occurs primarily from northward propagations of the convective cloud zone. There are important differences between the spatial patterns of the active/break spells and those characteristic of interannual variation, particularly those associated with the link to ENSO. Hence, the interannual variation of the Indian monsoon cannot be considered as primarily arising from the interannual variation of intraseasonal variation. However, the signature over the eastern equatorial Indian Ocean on intraseasonal time scales is similar to that on the interannual time scales.

Inhibition of peroxidase-catalyzed protein tyrosine nitration by antithyroid drugs and their analogues

In this paper, we describe the effect of some commonly used thiourea-based antithyroid drugs and their analogues on the peroxidase-catalyzed nitration reactions. The nitration of bovine serum albumin (BSA) and cytochrome c was studied using the antibody against 3-nitro-L-tyrosine. This study reveals that the thione-based antithyroid drugs effectively inhibit lactoperoxidase (LPO)-catalyzed nitration of BSA. These compounds show very weak inhibition towards the nitration of cytochrome c. Some of these compounds also inhibit myeloperoxidase (MPO)-catalyzed nitration of L-tyrosine. A structure-activity correlation study on the peroxidase-catalyzed nitration of L-tyrosine reveals that the presence of thione/selone moiety is important for the inhibition. Although the presence of a free N-H group adjacent to C=S moiety is necessary for most of the thiones to inhibit the LPO-catalyzed nitration, the corresponding selones do not require the presence of any free N-H group for their activity. Furthermore, experiments with different concentrations of H2O2 suggest that the antithyroid drugs and related thiones inhibit the nitration reaction mainly by coordinating to the Fe(III)-center of the enzyme active site as previously proposed for the inhibition of peroxidase-catalyzed iodination. On the other hand, the selenium compounds inhibit the nitration by scavenging H2O2 without interacting with the enzyme active site. This assumption is based on the observations that catalase effectively inhibits tyrosine nitration by scavenging H2O2, which is one of the substrates for the nitration. In contrast, superoxide dismutase (SOD) does not alter the nitration reactions, indicating the absence of superoxide radical anion (O-2 center dot(-)) during the peroxidase-catalyzed nitration reactions. (C) 2010 Elsevier B.V. All rights reserved.

Functional Mimics of Glutathione Peroxidase: Bioinspired Synthetic Antioxidants

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the biological system's ability to detoxify these reactive intermediates. Mammalian cells have elaborate antioxidant defense mechanisms to control the damaging effects of ROS. Glutathione peroxidase (GPx), a selenoenzyme, plays a key role in protecting the organism from oxidative damage by catalyzing the reduction of harmful hydroperoxides with thiol a ``catalytic triad'' with tryptophan and glutamine, which cofactors. The selenocysteine residue at the active site forms activates the selenium moiety for an efficient reduction of peroxides. After the discovery that ebselen, a synthetic organoselenium compound, mimics the catalytic activity of GPx both in vitro and in vivo, several research groups developed a number of small-molecule selenium compounds as functional mimics of GPx, either by modifying the basic structure of ebselen or by incorporating some structural features of the native enzyme. The synthetic mimics reported in the literature can be classified in three major categories: (i) cyclic selenenyl amides having a Se-N bond, (ii) diaryl diselenides, and (iii) aromatic or aliphatic monoselenides. Recent studies show that ebselen exhibits very poor GPx activity when aryl or benzylic thiols such as PhSH or BnSH are used as cosubstrates. Because the catalytic activity of each GPx mimic largely depends on the thiol cosubstrates used, the difference in the thiols causes the discrepancies observed in different studies. In this Account, we demonstrate the effect of amide and amine substituents on the GPx activity of various organoselenium compounds. The existence of strong Se ... O/N interactions in the selenenyl sulfide intermediates significantly reduces the GPx activity. These interactions facilitate an attack of thiol at selenium rather than at sulfur, leading to thiol exchange reactions that hamper the formation of catalytically active selenol. Therefore, any substituent capable of enhancing the nucleophilic attack of thiol at sulfur in the selenenyl sulfide state would enhance the antioxidant potency of organoselenium compounds. Interestingly, replacement of the sec-amide substituent by a tert-amide group leads to a weakening of Se ... 0 interactions in the selenenyl sulfide intermediates. This modification results in 10- to 20-fold enhancements in the catalytic activities. Another strategy involving the replacement of tert-amide moieties by tert-amino substituents further increases the activity by 3- to 4-fold. The most effective modification so far in benzylamine-based GPx mimics appears to be either the replacement of a tert-amino substituent by a sec-amino group or the introduction of an additional 6-methoxy group in the phenyl ring. These strategies can contribute to a remarkable enhancement in the GPx activity. In addition to enhancing catalytic activity, a change in the substituents near the selenium moiety alters the catalytic mechanisms. The mechanistic investigations of functional mimics are useful not only for understanding the complex chemistry at the active site of GPx but also for designing and synthesizing novel antioxidants and anti-inflammatory agents.

Donor properties of some flexidentate hydroxyimino-β-diketones in their rhodium(III) complexes

A series of rhodium(III) complexes of certain hydroxyimino-beta-diketones were synthesised and their structures assigned on the basis of elemental analyses and i.r. and1H n.m.r. spectral studies, The complexes exhibit coordination through carbonyl oxygen and nitrogen of the hydroxy-imino groups in the ligands.1H and13C n.m.r. studies show that the ligands exist in the isonitroso form in CDCl3.

Synthesis, structure and redox properties of (?-oxo)bis(?-carboxylato)diruthenium(III) complexes containing three different terminal ligands

Blue coloured, unstable, essentially diamagnetic and non-electrolytic diruthenium(III) complexes of the formation [Ru2O(O2CR)4(en)2(PPh3)2] were prepared by reacting [Ru2O(O2CR)4(PPh3)2] with 1,2-diaminoethane (en) in CH2Cl2 (R = C6H4-p-X; X = H, Me and OMe). The molecular structure of the complexes is proposed as [{(?1-O2CR)(?1-en)(PPH3)Ru}2(?-O)(?-O2CR)2] based on the 1H NMR spectral data. The electronic spectra of the complexes display a band near 569 nm with a shoulder at 630 nm. In CH2Cl2-0.1 M [Bun4N]ClO4, the complexes exhibit redox couples Ru2III,III/Ru2III,IV and Ru2III,IV/Ru2IV,IV near 0.1 and 1.2 V (vs SCE), respectively. The potentials are the lowest among diruthenium(III) complexes with a similar core structure.

On the large-scale diffuse magnetic field of the sun - II. The contribution of active regions

Dikpati and Choudhuri (1993, 1995) developed a model for the poleward migration of the weak diffuse magnetic field on the Sun's surface. This field was identified with the poloidal component produced by the solar dynamo operating at the base of the convection zone, and its evolution was studied by considering the effects of meridional circulation and turbulent diffusion. The earlier model is extended in this paper by incorporating the flux from, the decay of tilted active regions near the solar surface as an additional source of the poloidal field. This extended model can now explain various low-latitude features in the time-latitude diagram of the weak diffuse fields. These low-latitude features could not be accounted for in the earlier model, which was very successful in modeling the behavior at high latitudes. The time-latitude diagrams show that regions of a particular polarity often have 'tongues' of opposite polarity. Such tongues can be produced in the theoretical model by incorporating fluctuations in the source term arising out of the decaying active regions.

The physics of active membranes

We review recent work on the physical properties of model fluid membranes in nonequilibrium situations resembling those encountered in the living cell and contrast their properties with those of the more familiar membranes at thermal equilibrium. We survey models for the effect of (i) active pumps and (ii) active fission–fusion processes encountered in intracellular trafficking on the stability and fluctuations of fluid membranes. Our purpose is twofold: to highlight the exciting nonequilibrium phenomena that arise in biological systems, and to show how some crucial features of living systems, namely dissipative energy uptake and directed motion, can fruitfully be incorporated into physical models of biological interest.

Seismic hazard analysis of Lucknow considering local and active seismic gaps

The Himalayas are one of very active seismic regions in the world where devastating earthquakes of 1803 Bihar-Nepal, 1897 Shillong, 1905 Kangra, 1934 Bihar-Nepal, 1950 Assam and 2011 Sikkim were reported. Several researchers highlighted central seismic gap based on the stress accumulation in central part of Himalaya and the non-occurrence of earthquake between 1905 Kangra and 1934 Bihar-Nepal. The region has potential of producing great seismic event in the near future. As a result of this seismic gap, all regions which fall adjacent to the active Himalayan region are under high possible seismic hazard due to future earthquakes in the Himalayan region. In this study, the study area of the Lucknow urban centre which lies within 350 km from the central seismic gap has been considered for detailed assessment of seismic hazard. The city of Lucknow also lies close to Lucknow-Faizabad fault having a seismic gap of 350 years. Considering the possible seismic gap in the Himalayan region and also the seismic gap in Lucknow-Faizabad fault, the seismic hazard of Lucknow has been studied based on deterministic and the probabilistic seismic hazard analysis. Results obtained show that the northern and western parts of Lucknow are found to have a peak ground acceleration of 0.11-0.13 g, which is 1.6- to 2.0-fold higher than the seismic hazard compared to the other parts of Lucknow.

Active Dendrites Regulate Spectral Selectivity in Location-Dependent Spike Initiation Dynamics of Hippocampal Model Neurons

How does the presence of plastic active dendrites in a pyramidal neuron alter its spike initiation dynamics? To answer this question, we measured the spike-triggered average (STA) from experimentally constrained, conductance-based hippocampal neuronal models of various morphological complexities. We transformed the STA computed from these models to the spectral and the spectrotemporal domains and found that the spike initiation dynamics exhibited temporally localized selectivity to a characteristic frequency. In the presence of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, the STA characteristic frequency strongly correlated with the subthreshold resonance frequency in the theta frequency range. Increases in HCN channel density or in input variance increased the STA characteristic frequency and its selectivity strength. In the absence of HCN channels, the STA exhibited weak delta frequency selectivity and the characteristic frequency was related to the repolarization dynamics of the action potentials and the recovery kinetics of sodium channels from inactivation. Comparison of STA obtained with inputs at various dendritic locations revealed that nonspiking and spiking dendrites increased and reduced the spectrotemporal integration window of the STA with increasing distance from the soma as direct consequences of passive filtering and dendritic spike initiation, respectively. Finally, the presence of HCN channels set the STA characteristic frequency in the theta range across the somatodendritic arbor and specific STA measurements were strongly related to equivalent transfer-impedance-related measurements. Our results identify explicit roles for plastic active dendrites in neural coding and strongly recommend a dynamically reconfigurable multi-STA model to characterize location-dependent input feature selectivity in pyramidal neurons.

Carbohydrate-Appended Tumor Targeting Iron(III) Complexes Showing Photocytotoxicity in Red Light

Glucose-appended photocytotoxic iron(III) complexes of a tridentate Schiff base phenolate ligand Fe(bpyag) (L)] (NO3) (1-3), where bpyag is N,N-bis(2- pyridylmethyl)-2-aminoethyl-beta-D-glucopyranoside and H2L is 3-(2-hydroxyphenylimino)-1-phenylbutan-1-one (H(2)phap) in 1, 3-(2-hydroxyphenylimino)-9-anthrylbutan-1-one (H(2)anap) 2, and 3- (2-hydroxyphenylimino)-1-pyrenylbutan-1-one (H(2)pyap) in 3, were synthesized and characterized. The complex Fe(dpma)(anapn(NO3) (4), having bis-(2-pyridylmethyl)benzylamine (dpma), in which the glucose moiety of bpyag is substituted by a phenyl group, was used as a control, and the complex Fe(dpma)(anap)](PF6) (4a) was structurally characterized by X-ray crystallography. The structure shows a FeN4O2 core in a distorted octahedral geometry. The high-spin iron(III) complexes with magnetic moment value of similar to 5.9 mu(B) showed a low-energy phenolate-to-Fe(III) charge-transfer (CT) absorption band as a shoulder near 500 nm with a tail extending to 700 nm and an irreversible Fe(III)-Fe(II) redox couple near -0.6 V versus saturated calomel electrode. The complexes are avid binders to calf thymus DNA and showed photocleavage of supercoiled pUC19 DNA in red (647 nm) and green (532 nm) light. Complexes 2 and 3 displayed significant photocytotoxicity in red light, with an IC50 value of similar to 20 mu M in HeLa and HaCaT cells, and no significant toxicity in dark. The cell death is via an apoptotic pathway, by generation of reactive oxygen species. Preferential internalization of the carbohydrate-appended complexes 2 and 3 was evidenced in HeLa cells as compared to the control complex 4. A 5-fold increase in the cellular uptake was observed for the active complexes in HeLa cells. The photophysical properties of the complexes are rationalized from the density functional theory calculations.

A Gaussian network model study suggests that structural fluctuations are higher for inactive states than active states of protein kinases

We performed Gaussian network model based normal mode analysis of 3-dimensional structures of multiple active and inactive forms of protein kinases. In 14 different kinases, a more number of residues (1095) show higher structural fluctuations in inactive states than those in active states (525), suggesting that, in general, mobility of inactive states is higher than active states. This statistically significant difference is consistent with higher crystallographic B-factors and conformational energies for inactive than active states, suggesting lower stability of inactive forms. Only a small number of inactive conformations with the DFG motif in the ``in'' state were found to have fluctuation magnitudes comparable to the active conformation. Therefore our study reports for the first time, intrinsic higher structural fluctuation for almost all inactive conformations compared to the active forms. Regions with higher fluctuations in the inactive states are often localized to the aC-helix, aG-helix and activation loop which are involved in the regulation and/or in structural transitions between active and inactive states. Further analysis of 476 kinase structures involved in interactions with another domain/protein showed that many of the regions with higher inactive-state fluctuation correspond to contact interfaces. We also performed extensive GNM analysis of (i) insulin receptor kinase bound to another protein and (ii) holo and apo forms of active and inactive conformations followed by multi-factor analysis of variance. We conclude that binding of small molecules or other domains/proteins reduce the extent of fluctuation irrespective of active or inactive forms. Finally, we show that the perceived fluctuations serve as a useful input to predict the functional state of a kinase.