Bile acids in asymmetric synthesis and molecular recognition

This account summarizes the progress made in our laboratory towards the development of new uses of naturally occurring bile acids. Applications in Asymmetric Synthesis (intramolecular coupling, and intermolecular reactions) and Molecular Recognition are described with suitable examples.

Monoclonal antibodies in the study of architecture of plant viruses

Monoclonal antibodies have been used as probes to study the architecture of several plant viruses over the past decade. These studies complement the information obtained through X-ray crystallography and help in delineating epitopes on the surface of the virus. The monoclonal antibodies that recognize distinct epitopes also aid in unravelling the mechanisms of assembly/disassembly of virus particles. Group-specific and strain-specific monoclonal antibodies are widely used in the classification of viruses. The significant developments made in this emerging area are reviewed here with specific examples.

Cytochrome P4504f, a potential therapeutic target limiting neuroinflammation

Inflammatory processes are involved in the pathogenesis and/or progression of acute central nervous system (CNS) infection, traumatic brain injury and neurodegenerative disorders among others indicating the need for novel strategies to limit neuroinflammation. Eicosanoids including leukotrienes, particularly leukotriene B-4 (LTB4) are principle mediator(s) of inflammatory response, initiating and amplifying the generation of cytokines and chemokines. Cytochrome P450 (Cyp), a family of heme proteins mediate metabolism of xenobiotics and endogenous compounds, such as eicosanoids and leukotrienes. Cytochrome P4504F (Cyp4f) subfamily includes five functional enzymes in mouse. We cloned and expressed the mouse Cyp4f enzymes, assayed their relative expression in brain and examined their ability to hydroxylate the inflammatory cascade prompt LTB4 to its inactive 20-hydroxylated product. We then examined the role of Cyp4fs in regulating inflammatory response in vitro, in microglial cells and in vivo, in mouse brain using lipopolysacharide (LPS), as a model compound to generate inflammatory response. We demonstrate that mouse brain Cyp4fs are expressed ubiquitously in several cell types in the brain, including neurons and microglia, and modulate inflammatory response triggered by LPS, in vivo and in microglial cells, in vitro through metabolism of LTB4 to the inactive 20-hydroxy LTB4. Chemical inhibitor or shRNA to Cyp4fs enhance and inducer of Cyp4fs attenuates inflammatory response. Further, induction of Cyp4f expression lowers LTB4 levels and affords neuroprotection in microglial cells or mice exposed to LPS. Thus, catalytic activity of Cyp4fs is a novel target for modulating neuroinflammation through hydroxylation of LTB4. (C) 2011 Elsevier Inc. All rights reserved.

Conformational studies of the phosphazenyl side chain in cyclophosphazenes. Part 3. Crystal and molecular structure of N3P3Cl4(NEt2)(NPPh3)

The crystal structure of N3P3Cl4(NEt2)(NPPh3) has been determined. The crystals are orthorhombic, space group Pbca, with a= 8.208(1), b= 21.890(1), c= 31.722(2)Å, Z= 8, and m.p. = 146.5 °C. The structure was solved by direct methods and refined to a final R value of 0.045 for 2 025 independent reflections. The analysis reveals significant variations in the ring P–N bond lengths. The two nitrogenous substituents, NPPh3 and NEt2, reside on the same phosphorus atom. The latter, NEt2, has an almost exact type II conformation (the plane NC2 almost perpendicular to the local NPN plane)(the first observed for a dialkylamino-group in cyclophosphazenes), the former, NPPh3, deviates from type II towards type III (in type III the plane Pring–N–Pexo makes an angle of ca. 45° with the local N–P–N ring plane). The present structure is compared with others of triphenylphosphazenyl-cyclophosphazenes and the conformation of the NPPh3 substituent and its electron supply in the ground and perturbed states are discussed.

Thermodynamics and phase equilibria in the system Cu2O CuO ()Ga2O3

The standard Gibbs free energies of formation of CuAlO2 and CuAl2O4 were determined in the range 700° to 1100°C, using emf measurements on the galvanic cells (1) Pt,CuO +] Cu2O/CaO-ZrO2/O2,Pt; (2) Pt,Cu +] CuAlO2+] Al2O3/CaO-ZrO2/ Cu +] Cu2O,Pt; and (3) Pt,CuAl2O4+] CuAlO2+]Al2O3/CaO-ZrO2/O2,Pt. The results are compared with published information on the stability of these compounds. The entropy of transformation of CuO from tenorite to the rock-salt structure is evaluated from the present results and from earlier studies on the entropy of formation of spinels from oxides of the rock-salt and corundum structures. The temperatures corresponding to 3-phase equilibria in the system Cu2O-CuO-Al2O3 at specified O2 pressures calculated from the present results are discussed in reference to available phase diagrams.

Optical, electrical and dielectric properties of TiO(2)-SiO(2) films prepared by a cost effective sol-gel process

Titanium dioxide (TiO(2)) and silicon dioxide (SiO(2)) thin films and their mixed films were synthesized by the sol-gel spin coating method using titanium tetra isopropoxide (TTIP) and tetra ethyl ortho silicate (TEOS) as the precursor materials for TiO(2) and SiO(2) respectively. The pure and composite films of TiO(2) and SiO(2) were deposited on glass and silicon substrates. The optical properties were studied for different compositions of TiO(2) and SiO(2) sols and the refractive index and optical band gap energies were estimated. MOS capacitors were fabricated using TiO(2) films on p-silicon (1 0 0) substrates. The current-voltage (I-V) and capacitance-voltage (C-V) characteristics were studied and the electrical resistivity and dielectric constant were estimated for the films annealed at 200 degrees C for their possible use in optoelectronic applications. (C) 2011 Elsevier B.V. All rights reserved.

Dispersion and vaporization of biofuels and conventional fuels in a crossflow pre-mixer

In lean premixed pre-vaporized (LPP) combustion, controlled atomization, dispersion and vaporization of different types of liquid fuel in the premixer are the key factors required to stabilize the combustion process and improve the efficiency. The dispersion and vaporization process for biofuels and conventional fuels sprayed into a crossflow pre-mixer have been simulated and analyzed with respect to vaporization rate, degree of mixedness and homogeneity. Two major biofuels under investigation are Ethanol and Rapeseed Methyl Esters (RME), while conventional fuels are gasoline and jet-A. First, the numerical code is validated by comparing with the experimental data of single n-heptane and decane droplet evaporating under both moderate and high temperature convective air now. Next, the spray simulations were conducted with monodispersed droplets with an initial diameter of 80 mu m injected into a turbulent crossflow of air with a typical velocity of 10 m/s and temperature of around 800K. Vaporization time scales of different fuels are found to be very different. The droplet diameter reduction and surface temperature rise were found to be strongly dependent on the fuel properties. Gasoline droplet exhibited a much faster vaporization due a combination of higher vapor pressure and smaller latent heat of vaporization compared to other fuels. Mono-dispersed spray was adopted with the expectation of achieving more homogeneous fuel droplet size than poly-dispersed spray. However, the diameter histogram in the zone near the pre-mixer exit shows a large range of droplet diameter distributions for all the fuels. In order to improve the vaporization performance, fuels were pre-heated before injection. Results show that the Sauter mean diameter of ethanol improved from 52.8% of the initial injection size to 48.2%, while jet-A improved from 48.4% to 18.6% and RME improved from 63.5% to 31.3%. The diameter histogram showed improved vaporization performance of jet-A. (C) 2011 Elsevier Ltd. All rights reserved.

Experimental and Theoretical Studies of Unusual Four-Membered Metallacycles from Reactions of Group 4 Metallocene Bis(trimethylsilyl)-acetylene Complexes with the Sulfurdiimide Me3SiN=S=NSiMe3

The use of the sulfurdiimide RN=S=NR' (R = R' = SiMe3, 3) in reactions with group 4 metallocene bis(trimethylsilyl)-acetylene complexes of the type [Cp2M(L (eta(2)-Me3Si-C2SiMe3)] (1: M = Ti, no L; 2: M = Zr, L = pyridine) has led to the formation of four-membered metallacycles 4M containing the group 4 metal, nitrogen and sulfur. DFT calculations performed on compound 4Ti indicate that this complex is best described as a sigma-complex with cyclic delocalisation of the ring electrons. Moreover, pseudo-Jahn-Teller distortion plays a significant role in stabilising this complex.

Temperature dependent photoemission spectroscopy on lightly-doped sodium tungsten bronze

Temperature dependent photoemission studies on lightly doped (x = 0.025) sodium tungsten bronzes, NaxWO3 have been investigated by high-resolution photoemission spectroscopy. The experimental results show evidence for polaron formation at the valence band edge and the photoemission spectra taken in different modes of the electron analyzer suggest that the density of states at the valence band edge gradually moves to other k-points in the Brillouin zone with increasing temperature and explain the dynamics of polarons in the insulating disordered sodium tungsten bronzes. (C) 2012 Elsevier Ltd. All rights reserved.

Mutations in Drosophila Myosin Rod Cause Defects in Myofibril Assembly

The roles of myosin during muscle contraction are well studied, but how different domains of this protein are involved in myofibril assembly in vivo is far less understood. The indirect flight muscles (IFMs) of Drosophila melanogaster provide a good model for understanding muscle development and function in vivo. We show that two missense mutations in the rod region of the myosin heavy-chain gene, Mhc, give rise to IFM defects and abnormal myofibrils. These defects likely result from thick filament abnormalities that manifest during early sarcomere development or later by hypercontraction. The thick filament defects are accompanied by marked reduction in accumulation of flightin, a myosin binding protein, and its phosphorylated forms, which are required to stabilise thick filaments. We investigated with purified rod fragments whether the mutations affect the coiled-coil structure, rod aggregate size or rod stability. No significant changes in these parameters were detected, except for rod thermodynamic stability in one mutation. Molecular dynamics simulations suggest that these mutations may produce localised rod instabilities. We conclude that the aberrant myofibrils are a result of thick filament defects, but that these in vivo effects cannot be detected in vitro using the biophysical techniques employed. The in vivo investigation of these mutant phenotypes in IFM development and function provides a useful platform for studying myosin rod and thick filament formation generically, with application to the aetiology of human myosin rod myopathies. (C) 2012 Elsevier Ltd. All rights reserved.

Electrical conductivity of Ca-doped YFeO3

Electrical conductivity and Seebeck coefficient of calcium-doped YFeO3, a potential cathode material in solid oxide fuel cells (SOFC), are measured as function of temperature and composition in air to resolve conflicts in the literature both on the nature of conduction (n- or p-type) and the types of defects (majority and the minority) present. Compositions of Y1-xCaxFeO3-delta with x = 0.0, 0.025, 0.05 and 0.1 are studied in the temperature range from 625 to 1250 K. All Y1-xCaxFeO3-delta samples show p-type semiconducting behaviour. Addition of Ca up to 5% dramatically increases the conductivity of YFeO3; increase is more gradual up to 10%. A second phase Ca2Fe2O5 appears in the microstructure for Ca concentrations in excess of 11%.

Dynamics of end-to-end loop formation: A flexible chain in the presence of hydrodynamic interaction

Based on the Wilemski-Fixman approach G. Wilemski, M. Fixman, J. Chem. Phys. 60 (1974) 866], we show that, for a flexible chain in theta solvent, hydrodynamic interaction treated with a pre-averaging approximation makes ring closing faster if the chain is not very short. We also show that the ring closing time for a long chain with hydrodynamic interaction in theta solvent scales with the chain length (N) as N-1.5, in agreement with the previous renormalization group calculation based prediction by Freidman and O'Shaughnessy B. Friedman, B. O'Shaughnessy, Phys. Rev. A 40 (1989) 5950]. (C) 2012 Elsevier B.V. All rights reserved.

Climatic fluctuations during the LIA and post-LIA in the Kumaun Lesser Himalaya, India: Evidence from a 400 y old stalagmite record

This paper presents the first stable isotope (delta O-18 and delta C-13) data of a similar to 400 years (1590-2006 AD) long annual to decadal-resolution speleothem record collected from the Indian Lesser Himalaya. The data show a variation from -2.7 to -5.9 parts per thousand in delta O-18 and -5.3 to -8.8 parts per thousand in delta C-13. The isotopic analyses indicate that the climate during this period can be divided into two stages: a wet phase during the Little Ice Age (LIA) (1590-1850 AD) and comparatively dry phase during the post-LIA after 1850 AD. However, the record also documents the minor dry events during the LIA and a wet episode after the LIA. Within the age uncertainty, the dry spells during the LIA are linked with the historical drought events in the Indian subcontinent and similar latitudes. The isotopic record is consistent with a number of previous studies in the areas influenced by the Westerlies but appears to be conflicting to the regions, dominated by the Indian Summer Monsoon (ISM). This may be due to the possible changes in the strength of Westerlies in the study area and added by negative anomaly of North Atlantic Oscillation (NAO) during the LIA. (C) 2012 Elsevier Ltd and INQUA. All rights reserved.

An association and Wilson activity coefficient model for solubilities of aromatic solid pollutants in supercritical carbon dioxide

The solubilities of various solid pollutants in supercritical carbon dioxide were investigated. The intermolecular interactions play a significant role in determining the solubilities of solids in supercritical carbon dioxide. A new model equation was derived by using the concepts of association and activity coefficient model to correlate the solubilities of solids. The model equation combines the association and Wilson activity coefficient models and includes the interaction potentials between the molecules, which are useful in understanding the behavior of the solid solutes in SCCO2. The new model equation involves five adjustable parameters to correlate the solubilities of solids by incorporating the interactions between the molecules. The equation correlated 75 solid systems with an average AARD of around 9%, which was better than the correlations obtained from standard models such as Mendez Santiago-Teja (MT) model and association model. (C) 2012 Elsevier B.V. All rights reserved.