Synthesis, DNA binding, docking and photocleavage studies of quinolinyl chalcones

A series of simple quinoline-chalcone conjugates have been synthesized by Claisen-Schmidt condensation reactions of substituted acetophenones with 2-chloro-3-formyl-quinoline and evaluated for their nucleolytic activity. The structures of the synthesized quinoline-chalcone conjugates were confirmed by IR, H-1 NMR, C-13 NMR and mass spectral analyses. Most of the prepared compounds showed significant DNA binding and photocleavage activities. The incorporation of an electron-donating group into ring A caused a moderate increase in the DNA binding and photocleavage activities. Compounds 3c and 3d exhibited promising DNA photocleavage against pUC 19 DNA with 85% inhibition at 100 mu M concentration. A structure-activity relationship analysis of these compounds was performed; compounds 3c and 3d are potential candidates for future drug discovery and development.

Low temperature magnetoresistance and magnetization studies of iron encapsulated multiwall carbon nanotube/polyvinyl chloride composites

We present the experimental results of temperature dependent magnetoresistance (MR) and the magnetization studies of iron encapsulated multiwall carbon nanotube (MWCNT)/polyvinyl chloride (PVC) composites with different wt% of MWCNTs. Transmission electron microscopy characterization shows that MWCNTs are encapsulated with rod-shaped iron nanoparticles of aspect ratio of similar to 3. The MR behavior of 1.9 wt% MWCNT/PVC sample shows dominance of forward scattering and wave function shrinkage whereas, weak localization and electron-electron interactions explain the MR data of higher wt% samples (9.1, 16.6 and 44.4 wt%). The composites of 4.7 and 9.1 wt% exhibit ferromagnetic behavior at all temperatures with room temperature coercivities of similar to 1036 and 628 Oe, respectively. (C) 2014 Elsevier Ltd. All rights reserved.

Directing peptide conformation with centrally positioned pre-organized dipeptide segments: studies of a 12-residue helix and beta-hairpin

Secondary structure formation in oligopeptides can be induced by short nucleating segments with a high propensity to form hydrogen bonded turn conformations. Type I/III turns facilitate helical folding while type II'/I' turns favour hairpin formation. This principle is experimentally verified by studies of two designed dodecapeptides, Boc-Val-Phe-Leu-Phe-Val-Aib-Aib-Val-Phe-Leu-Phe-Val-OMe 1 and Boc-Val-Phe-Leu-Phe-Val- (D) Pro- (L) Pro-Val-Phe-Leu-Phe-Val-OMe 2. The N- and C-terminal flanking pentapeptide sequences in both cases are identical. Peptide 1 adopts a largely alpha-helical conformation in crystals, with a small 3(10) helical segment at the N-terminus. The overall helical fold is maintained in methanol solution as evidenced by NMR studies. Peptide 2 adopts an antiparallel beta-hairpin conformation stabilized by 6 interstrand hydrogen bonds. Key nuclear Overhauser effects (NOEs) provide evidence for the antiparallel beta-hairpin structure. Aromatic proton chemical shifts provide a clear distinction between the conformation of peptides 1 (helical) and 2 (beta-hairpin). The proximity of facing aromatic residues positioned at non-hydrogen bonding positions in the hairpin results in extensively ring current shifted proton resonances in peptide 2.

Antimicrobial Peptides with Potential for Biofilm Eradication: Synthesis and Structure Activity Relationship Studies of Battacin Peptides

We report on the first chemical syntheses and structureactivity analyses of the cyclic lipopeptide battacin which revealed that conjugation of a shorter fatty acid, 4-methyl-hexanoic acid, and linearization of the peptide sequence improves antibacterial activity and reduces hemolysis of mouse blood cells. This surprising finding of higher potency in linear lipopeptides than their cyclic counterparts is economically beneficial. This novel lipopeptide was membrane lytic and exhibited antibiofilm activity against Pseudomonas aeruginosa, Staphylococcus aureus, and, for the first time, Pseudomonas syringe pv. actinidiae. The peptide was unstructured in aqueous buffer and dimyristoylphosphatidylcholine-polymerized diacetylene vesicles, with 12% helicity induced in 50% v/v of trifluoroethanol. Our results indicate that a well-defined secondary structure is not essential for the observed antibacterial activity of this novel lipopeptide. A truncated pentapeptide conjugated to 4-methyl hexanoic acid, having similar potency against Gram negative and Gram positive pathogens was identified through alanine scanning.

Structural, thermal and quantum chemical studies of p-coumaric and caffeic acids

Two hydroxycinnamic acids viz., p-coumaric, and caffeic acids have been extracted and purified from Parthenium hysterophorus, subsequently characterized by elemental analysis, FT-IR, NMR, single crystal X-ray crystallography. The optimized structures of these acids were calculated in terms of density functional theory by Gaussian 09. The validation of experimental and theoretically obtained data for structural parameters such as bond lengths and bond angles has have been carried out to analyze the statistical significance by curve fitting analysis and the values of correlation coefficient found to be 0.985, 0.992, and 0.984, 0.975 in p-coumaric, and caffeic acids, respectively. The calculated HOMO and LUMO energies show the eventual charge transfer interaction within the molecule. Thermal studies were also carried out by thermogravimetry (TG), differential thermogravimetric analysis (DTA), and derivative thermogravimetry (DTG). (C) 2014 Elsevier B.V. All rights reserved.

Conductivity Studies of Silver-, Potassium-, and Magnesium-Doped Hydroxyapatite

We report the electrical transport properties of silver-, potassium-, and magnesium-doped hydroxyapatites (HAs). While Ag+ or K+ doping to HA enhances the conductivity, Mg+2 doping lowers the conductivity when compared with undoped HA. The mechanism behind the observed differences in ionic conductivity has been discussed using the analysis of high-temperature frequency-dependent conductivity data, Cole-Cole plots of impedance data as well as on the basis of the frequency dependence of the imaginary part (M) of the complex electric modulus. The f(max) of modulus M decreased in silver- and potassium-doped samples in comparison with the undoped HA.

Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(I/II) complexes of thiosemicarbazone: special emphasis on their interactions with DNA

4-(p-X-phenyl)thiosemicarbazone of napthaldehyde {where X = Cl (HL1) and X = Br (HL2)}, thiosemicarbazone of quinoline-2-carbaldehyde (HL3) and 4-(p-fluorophenyl) thiosemicarbazone of salicylaldehyde (H2L4) and their copper(I) {Cu(HL1)(PPh3)(2)Br]center dot CH3CN (1) and Cu(HL2)(PPh3)(2)Cl]center dot DMSO (2)} and copper(II) {((Cu2L2Cl)-Cl-3)(2)(mu-Cl)(2)]center dot 2H(2)O (3) and Cu(L-4)(Py)] (4)} complexes are reported herein. The synthesized ligands and their copper complexes were successfully characterized by elemental analysis, cyclic voltammetry, NMR, ESI-MS, IR and UV-Vis spectroscopy. Molecular structures of all the Cu(I) and Cu(II) complexes have been determined by X-ray crystallography. All the complexes (1-4) were tested for their ability to exhibit DNA-binding and - cleavage activity. The complexes effectively interact with CT-DNA possibly by groove binding mode, with binding constants ranging from 10(4) to 10(5) M-1. Among the complexes, 3 shows the highest chemical (60%) as well as photo-induced (80%) DNA cleavage activity against pUC19 DNA. Finally, the in vitro antiproliferative activity of all the complexes was assayed against the HeLa cell line. Some of the complexes have proved to be as active as the clinical referred drugs, and the greater potency of 3 may be correlated with its aqueous solubility and the presence of the quinonoidal group in the thiosemicarbazone ligand coordinated to the metal.

Spatio-temporal correlations in aqueous systems: computational studies of static and dynamic heterogeneity by 2D-IR spectroscopy

Local heterogeneity is ubiquitous in natural aqueous systems. It can be caused locally by external biomolecular subsystems like proteins, DNA, micelles and reverse micelles, nanoscopic materials etc., but can also be intrinsic to the thermodynamic nature of the aqueous solution itself (like binary mixtures or at the gas-liquid interface). The altered dynamics of water in the presence of such diverse surfaces has attracted considerable attention in recent years. As these interfaces are quite narrow, only a few molecular layers thick, they are hard to study by conventional methods. The recent development of two dimensional infra-red (2D-IR) spectroscopy allows us to estimate length and time scales of such dynamics fairly accurately. In this work, we present a series of interesting studies employing two dimensional infra-red spectroscopy (2D-IR) to investigate (i) the heterogeneous dynamics of water inside reverse micelles of varying sizes, (ii) supercritical water near the Widom line that is known to exhibit pronounced density fluctuations and also study (iii) the collective and local polarization fluctuation of water molecules in the presence of several different proteins. The spatio-temporal correlation of confined water molecules inside reverse micelles of varying sizes is well captured through the spectral diffusion of corresponding 2D-IR spectra. In the case of supercritical water also, we observe a strong signature of dynamic heterogeneity from the elongated nature of the 2D-IR spectra. In this case the relaxation is ultrafast. We find remarkable agreement between the different tools employed to study the relaxation of density heterogeneity. For aqueous protein solutions, we find that the calculated dielectric constant of the respective systems unanimously shows a noticeable increment compared to that of neat water. However, the `effective' dielectric constant for successive layers shows significant variation, with the layer adjacent to the protein having a much lower value. Relaxation is also slowest at the surface. We find that the dielectric constant achieves the bulk value at distances more than 3 nm from the surface of the protein.

NUMERICAL STUDIES OF DYNAMO ACTION IN A TURBULENT SHEAR FLOW. I.

We perform numerical experiments to study the shear dynamo problem where we look for the growth of a large-scale magnetic field due to non-helical stirring at small scales in a background linear shear flow in previously unexplored parameter regimes. We demonstrate the large-scale dynamo action in the limit where the fluid Reynolds number (Re) is below unity while the magnetic Reynolds number (Rm) is above unity; the exponential growth rate scales linearly with shear, which is consistent with earlier numerical works. The limit of low Re is particularly interesting, as seeing the dynamo action in this limit would provide enough motivation for further theoretical investigations, which may focus attention on this analytically more tractable limit of Re < 1 compared to the more formidable limit of Re > 1. We also perform simulations in the regimes where (i) both (Re, Rm) < 1, and (ii) Re > 1 and Rm < 1, and compute all of the components of the turbulent transport coefficients (alpha(ij) and alpha(ij)) using the test-field method. A reasonably good agreement is observed between our results and the results of earlier analytical works in similar parameter regimes.

Temperature-Dependent Magnetic and EPR Studies of Bulk and Nanoparticles of Bi0.1Ca0.9MnO3

We report temperature-dependent magnetic and electron paramagnetic resonance (EPR) properties of bulk and nanoparticle samples of Bi0.1Ca0.9MnO3 (BCMO). The nanoparticles of BCMO (dia similar to 50 nm) were prepared by the standard sol-gel technique and bulk samples by solid-state reaction method. We have investigated the magnetic ordering in the two samples by carrying out temperature-dependent magnetic and EPR studies and compared their properties. According to earlier reports, antiferromagnetic and ferromagnetic orders coexist in the bulk sample of Bi0.1Ca0.9MnO3. Our magnetization and EPR results show the existence of ferromagnetism in the bulk sample which is present in the nanosample as well but with somewhat weakened strength with the size reduction.

Antiproliferative and tumor inhibitory studies of 2,3 disubstituted 4-thiazolidinone derivatives

4-Thiazolidinone derivatives were synthesized using T3P (R)-DMSO media as a cyclodehydrating agent. All the molecules were tested for their cytotoxicity against leukemic cell lines. The compound 3-(4-bromophenyl)-2-(4-(dimethylamino)phenyl)thiazolidin-4-one (4e) with electron donating substituent at para position of phenyl ring displayed considerable cytotoxicity against Reh and Nalm6 cells with an IC50 value of 11.9 and 13.5 mu M, respectively. Furthermore, the compound 4e tested for tumor regression studies induced by EAC in Swiss albino mouse. Both in vitro and in vivo results suggested significant antiproliferative activity of compound 4e in Reh cells and mouse tumor tissue treated with compound 4e showed multifocal areas of necrosis and numerous number of apoptotic cells. (C) 2015 Elsevier Ltd. All rights reserved.

Crystallographic studies of the extracytoplasmic function sigma factor sigma(J) from Mycobacterium tuberculosis

Mycobacterium tuberculosis has multiple sigma factors which enable the bacterium to reprogram its transcriptional machinery under diverse environmental conditions. sigma(J), an extracytoplasmic function sigma factor, is upregulated in late stationary phase cultures and during human macrophage infection. sigma(J) governs the cellular response to hydrogen peroxide-mediated oxidative stress. sigma(J) differs from other canonical sigma factors owing to the presence of a SnoaL_2 domain at the C-terminus. sigma(J) crystals belonged to the tetragonal space group I422, with unit-cell parameters a = b = 133.85, c = 75.08 angstrom. Diffraction data were collected to 2.16 angstrom resolution on the BM14 beamline at the European Synchrotron Radiation Facility (ESRF).

Electron Magnetic Resonance Studies of Nanosized Nd0.65Ca0.35 Mn1-xCrxO3 (x=0, 0.06, 0.1) Manganite

We report a systematic investigation of the temperature dependence of electron magnetic resonance (EMR) line width, intensity and resonance field for similar to 25 nm Nd0.65Ca0.35MnO3 (NCMO1), Nd0.65Ca0.35Mn0.94Cr0.06O3 (NCMO2) and Nd0.65Ca0.35Mn0.9Cr0.1O3 (NCMO3) nanoparticles prepared by sol-gel method. The EMR line widths for the three nano-samples differ significantly from one another below a temperature T (min) where the line width has a minimum. T (min) was found to be 130, 100 and 120 K for NCMO1, NCMO2 and NCMO3, respectively. Well above T (min) the line width values for the three samples are close to one another. The sharp upturn of EMR line width below T (min) is attributed to the formation of short range, ferromagnetically ordered clusters. Temperature dependence of EMR intensity shows a residual CO transition in NCMO1 and NCMO2 and a complete disappearance of it in NCMO3. The intensity undergoes significant increase below 120, 80 and 100 K for NCMO1, NCMO2 and NCMO3, respectively, indicating the onset of ferromagnetic transitions. The occurrence of ferromagnetic transition is further confirmed by magnetization hysteresis measurements. The decrease in T (C) in NCMO2 and NCMO3 compared to NCMO1 nanoparticles is understood to be due to the destruction of the double-exchange interaction by chromium doping. The resonance field decreases below the ferromagnetic onset temperatures for all the samples as expected. The combined effects of the reduction in size and of chromium doping in Mn site are discussed.

The X-ray photoelectron spectroscopy and high-temperature structural studies of Zn1-xNixO/NiO two-phase composites

Detailed investigation of the chemical states and local atomic environment of Ni and Zn in the two-phase composites of Zn1-xNixO/NiO was reported. The X-ray photoelectron spectra of both Ni-2p and Zn-2p revealed the existence of a doublet with spin-orbit splitting approximate to 17.9 and 23.2eV, respectively confirming the divalent oxidation state of both Ni and Zn. However, the samples fabricated under oxygen-rich conditions exhibit significant difference in the binding energy approximate to 18.75eV between the 2p3/2 and 2p1/2 states of Ni. The shift in the satellite peaks of Ni-2p with increasing the Ni composition x within the Zn1-xNixO/NiO matrix signifies the attenuation of nonlocal screening because of reduced site occupancy of two adjacent Zn ions. The temperature dependence of X-ray diffraction analysis reveals a large distortion in the axial-rhombohedral angle for oxygen-rich NiO. Conversely, no significant distortion was noticed in the NiO system present as a secondary phase within Zn1-xNixO. Nevertheless, the unit-cell volume of both wurtzite h.c.p. Zn1-xNixO and f.c.c. NiO exhibits an anomalous behavior between 150 and 300 degrees C. The origin of such unusual change in the unit-cell volume was discussed in terms of oxygen stoichiometry.