Design, Synthesis, and DNA Binding Properties of Photoisomerizable Azobenzene−Distamycin Conjugates: An Experimental and Computational Study

Here, we present the synthesis, photochemical, and DNA binding properties of three photoisomerizable azobenzene−distamycin conjugates in which two distamycin units were linked via electron-rich alkoxy or electron-withdrawing carboxamido moieties with the azobenzene core. Like parent distamycin A, these molecules also demonstrated AT-specific DNA binding. Duplex DNA binding abilities of these conjugates were found to depend upon the nature and length of the spacer, the location of protonatable residues, and the isomeric state of the conjugate. The changes in the duplex DNA binding efficiency of the individual conjugates in the dark and with their respective photoirradiated forms were examined by circular dichroism, thermal denaturation of DNA, and Hoechst displacement assay with poly[d(A-T).d(T-A)] DNA in 150 mM NaCl buffer. Computational structural analyses of the uncomplexed ligands using ab initio HF and MP2 theory and molecular docking studies involving the conjugates with duplex d[(GC(AT)10CG)]2 DNA were performed to rationalize the nature of binding of these conjugates.

Crystal structure of 3-acetylcoumarin-o-aminobenzoylhydrazone and synthesis, spectral and thermal studies of its transition metal complexes

Transition metal [Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II)] complexes of a new Schiff base, 3-acetylcoumarin-o-aminobenzoylhydrazone were synthesized and characterized by elemental analyses, magnetic moments, conductivity measurements, spectral [Electronic, IR, H-1 and C-13 NMR, EPR] and thermal studies. The ligand crystallizes in the monoclinic system, space group P2(1)/n with a = 9.201(5), b = 16.596( 9), c = 11.517(6) angstrom, beta= 101.388(9)degrees, V = 1724.2 (17) angstrom(3) and Z = 4. Conductivity measurements indicated Mn(II) and Co(II) complexes to be 1 : 1 electrolytes whereas Ni(II), Cu(II), Zn(II) and Cd(II) complexes are non-electrolytes. Electronic spectra reveal that all the complexes possess four-coordinate geometry around the metal.

Structural Insights into the acyl-intermediates of plasmodium falciparum fatty acid synthesis pathway; the mechanism of expansion of acyl carrier protein core

Acyl carrier protein (ACP) plays a central role in fatty acid biosynthesis. However, the molecular machinery that mediates its function is not yet fully understood. Therefore, structural studies were carried out on the acyl-ACP intermediates of Plasmodium falciparum using NMR as a spectroscopic probe. Chemical shift perturbation studies put forth a new picture of the interaction of ACP molecule with the acyl chain, namely, the hydrophobic core can protect up to 12 carbon units, and additional carbons protrude out from the top of the hydrophobic cavity. The latter hypothesis stems from chemical shift changes observed in C-alpha and C-beta of Ser-37 in tetradecanoyl-ACP. C-13, N-15-Double-filtered nuclear Overhauser effect (NOE) spectroscopy experiments further substantiate the concept; in octanoyl (C-8)- and dodecanoyl (C-12)-ACP, a long range NOE is observed within the phosphopantetheine arm, suggesting an arch-like conformation. This NOE is nearly invisible in tetradecanoyl (C-14)-ACP, indicating a change in conformation of the prosthetic group. Furthermore, the present study provides insights into the molecular mechanism of ACP expansion, as revealed from a unique side chain-to-backbone hydrogen bond between two fairly conserved residues, Ile-55 HN and Glu-48 O. The backbone amide of Ile-55 HN reports a pK(a) value for the carboxylate, similar to 1.9 pH units higher than model compound value, suggesting strong electrostatic repulsion between helix II and helix III. Charge-charge repulsion between the helices in combination with thrust from inside due to acyl chain would energetically favor the separation of the two helices. Helix III has fewer structural restraints and, hence, undergoes major conformational change without altering the overall-fold of P. falciparum ACP.

Synthesis and bioassay of a new class of heterocycles pyrrolyl oxadiazoles/thiadiazoles/triazoles

A new class of heterocycles pyrrolyl thiadiazoles, pyrrolyl oxadiazoles and pyrrolyl triazoles were prepared from arylsulfonylethenesulfonylacetic acid methyl ester and tested for their antimicrobial and cytotoxic activities. (C) 2008 Elsevier Masson SAS. All rights reserved.

Synthesis, spectral characterization, in-vitro microbiological evaluation and cytotoxic activities of novel macrocyclic bis hydrazone

A macrocyclic hydrazone Schiff base was synthesized by reacting 1,4-dicarbonyl phenyl dihydrazide with 2,6-diformyl-4-methyl phenol and a series of metal complexes with this new Schiff base were synthesized by reaction with Co(II), Ni(II) and Cu(II) metal salts. The Schiff base and its complexes have been characterized by elemental analyses, IR, H-1 NMR, UV-vis, FAB mass, ESR spectra, fluorescence, thermal, magnetic and molar conductance data. The analytical data reveal that the Co(II), Ni(II) and Cu(II) complexes possess 2:1 metal-ligand ratios. All the complexes are non-electrolytes in DMF and DMSO due to their low molar conductance values. Infrared spectral data suggest that the hydrazone Schiff base behaves as a hexadentate ligand with NON NON donor sequence towards the metal ions. The ESR spectral data shows that the metal-ligand bond has considerable covalent character. The electrochemical behavior of the copper(II) complex was investigated by cyclic voltammetry. The Schiff base and its complexes have also been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Shigella dysentery, Micrococcus, Bacillus subtilis, Bacillus cereus and Pseudomonas aeruginosa) and antifungal activities (Aspergillus niger, Penicillium and Candida albicans) by MIC method. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties. (C) 2009 Elsevier Masson SAS. All rights reserved.

Why do birds participate in mixed-species foraging flocks? A large-scale synthesis

Mixed-species flocks of foraging birds have been documented from terrestrial habitats all over the world and are thought to form for either improved feeding efficiency or better protection from predators. Two kinds of flock participants are recognized: those that join other species ('followers') and are therefore likely to be the recipients of the benefits of flock participation and those that are joined ('leaders'). Through comparative analyses, using a large sample of flocks from around the world, we show that (1) 'followers' tend to be smaller, more insectivorous, and feed in higher strata than matched species that participate in flocks to a lesser extent and (2) 'leaders' tend to be cooperative breeders more often than matched species that are not known to lead flocks. Furthermore, meta-analyses of published results from across the world showed that bird species in terrestrial mixed-species flocks increase foraging rates and reduce vigilance compared to when they are solitary or in conspecific groups. Moreover, the increase in foraging rates is seen only with flock followers and not flock leaders. These findings suggest a role for predation in the evolution of mixed-species flocking. Species that are vulnerable to predation follow species whose vigilance they can exploit. By doing so, they are able to reduce their own vigilance and forage at higher rates. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Facile one-pot synthesis of thio and selenourea derivatives: A new class of potent urease inhibitors

A facile, one-pot synthesis of thio and selenourea derivatives from amines using tetrathiomolybdate 1 and tetraseleno-tungstate 2 as sulfur and selenium transfer reagents, respectively, is reported. The compounds were tested for their activity as urease inhibitors and some of the compounds showed potent activity in the nanomolar range towards jack bean urease. (C) 2007 Elsevier Ltd. All rights reserved.

Conformationally locked thiosugars alpha-mannosidase inhibitors: Synthesis, and docking studies as potent biochemical

series of thiosugar derivatives (thiolevomannosans) derived from mannose were synthesized and their inhibitory activity was tested against alpha-mannosidase (jack bean). These inhibitors were found to be more potent than the well-known inhibitors like kifunensine and deoxymannojirimycin based on docking and biochemical studies. The sulfone derivative 10 was shown to be the best inhibitor of alpha-mannosidase with the K-i value of 350 nM. (c) 2007 Elsevier Ltd. All rights reserved.

Enantiospecific synthesis of ABC-ring system of A-nor and abeo 4(3 -> 2) tetra and pentacyclic triterpenes

Enantiospecific synthesis of ABC-ring systems of A-nor and abeo 4(3 -> 2) tetra and pentacyclic triterpenes has been accomplished starting from the readily available monoterpene (R)-carvone. (R)-Carvone was used as the B-ring of the target molecules. A lithium-liquid ammonia mediated cyclisation of delta,epsilon-unsaturated ester was employed for the cyclopentannulation at the C-5 and C-6 carbons of carvone and an RCM reaction was employed for the cyclohexannulation to generate the ABC-ring system of A-nor tetra and pentacyclic triterpenes. The strategy has been extended for the synthesis of the ABC-ring system of abeo 4(3 -> 2) tetra and pentacyclic triterpenes. (C) 2009 Elsevier Ltd. All rights reserved.

Synthesis and structural characterization of a new ruthenium hydride ethylene complex

A ruthenium(II) ethylene complex, trans-[Ru(H)(C2H4)- (dppm)(2)][BF4], hearing two 1,1-bis(diphenylphosphino) methane (dppm) ligands has been synthesized and structurally characterized using X-ray crystallography. In the molecular structure, the Ru-II center shows a distorted octahedral coordination geometry formed by four P atoms of the two chelating dppm ligands, a hydride, and an ethylene ligands. The four dppm P atoms are almost co-planar with the hydride and the ethylene ligands perpendicular to this plane. The C-C bond distance of the bound ethylene is 1.375(6) angstrom, which is elongated by 0.042 angstrom as compared to free ethylene (1.333(2) angstrom). The packing diagram of the complex shows two voids or channels, which are occupied by BF4- counterion and water molecules.

Enantiospecific synthesis of thaps-8-en-5-ol via stereospecific intramolecular chirality transfer

Enantiospecific synthesis of thaps-8-en-5-ol, comprising of the carbon framework of a small group of sesquiterpenes containing three contiguous quaternary carbon atoms has been described. (R)-Carvone has been employed as the chiral starting material and a combination of intramolecular alkyation and Criegec fragmentation have been employed for intramolecular stereospecific transfer of the chirality. An intramolecular diazoketone cyclopropanation and regioselective cyclopropane ring cleavage reactions have been employed for the creation of the three requisite contiguous quaternary carbon atoms.

Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis

Osteoporosis is a disease of low bone mass most often caused by an increase in bone resorption that is not sufficiently compensated for by a corresponding increase in bone formation(1). As gut-derived serotonin (GDS) inhibits bone formation(2), we asked whether hampering its biosynthesis could treat osteoporosis through an anabolic mechanism (that is, by increasing bone formation). We synthesized and used LP533401, a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis. Oral administration of this small molecule once daily for up to six weeks acts prophylactically or therapeutically, in a dose-dependent manner, to treat osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. These results provide a proof of principle that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis.

Synthesis of Diketopyrrolopyrrole Containing Copolymers: A Study of Their Optical and Photovoltaic Properties

The diketopyrrolopyrrole-based copolymers PDPP-BBT and TDPP-BBT were synthesized and used as donor for bulk heterojunction photovoltaic devices. The photophysical properties of these polymers showed absorption in the range 500-600 nm with a maximum peak around 563 nm, while TDPP-BBT showed broadband absorption in the range 620 - 800 nm with a peak around 656 nm. The power conversion efficiencies (PCE) of the polymer solar cells based on these copolymers and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) were 0.68% (as cast PDPP-BBT:PCBM), 1.51% (annealed PDPP-BBT:PCBM), 1.57% (as cast TDPPBBT: PCBM), and 2.78% (annealed TDPP-BBT:PCBM), under illumination of AM 1.5 (100 mW/cm2). The higher PCE for TDPP-BBT-based polymer solar cells has been attributed to the low band gap of this copolymer as compared to PDPP-BBT, which increases the numbers of photogenerated excitons and corresponding photocurrent of the device. These results indicate that PDPP-BBT and TDPP-BBT act as excellent electron donors for bulk heterojunction devices.

Process variables in biomimetic synthesis of silver nanoparticles by aqueous extract of Azadirachta indica (Neem) leaves

Owing to widespread applications, synthesis and characterization of silver nanoparticles is recently attracting considerable attention. Increasing environmental concerns over chemical synthesis routes have resulted in attempts to develop biomimetic approaches. One of them is synthesis using plant parts, which eliminates the elaborate process of maintaining the microbial culture and often found to be kinetically favourable than other bioprocesses. The present study deals with investigating the effect of process variables like reductant concentrations, reaction pH, mixing ratio of the reactants and interaction time on the morphology and size of silver nanoparticles synthesized using aqueous extract of Azadirachta indica (Neem) leaves. The formation of crystalline silver nanoparticles was confirmed using X-ray diffraction analysis. By means of UV spectroscopy, Scanning and Transmission Electron Microscopy techniques, it was observed that the morphology and size of the nanoparticles were strongly dependent on the process parameters. Within 4 h interaction period, nanoparticles below 20-nm-size with nearly spherical shape were produced. On increasing interaction time (ageing) to 66 days, both aggregation and shape anisotropy (ellipsoidal, polyhedral and capsular) of the particles increased. In alkaline pH range, the stability of cluster distribution increased with a declined tendency for aggregation of the particles. It can be inferred from the study that fine tuning the bioprocess parameters will enhance possibilities of desired nano-product tailor made for particular applications.

Microwave-Assisted Synthesis of NiO Nanoparticles

NiO has been synthesized by microwave-induced chemical synthesis route using metalorganic complex of nickel in a domestic-type microwave oven (2.45 GHz). A novel metalorganic complex of nickel, viz., a beta-ketoester of nickel, synthesized and characterized as apart of this work, was employed as the precursor material. We varied the experimental parameters, such as the choice of solvent and microwave power, to obtain nanoparticles of NiO. The NiO nanoparticles were characterized by XRD, SEM, and TEM. The particle size of the NiO was found to vary from 7-40 nm. The magnetic behavior of the nanoparticles of NiO was examined with a vibrating sample magnetometer, revealing that as the particle size diminishes, the magnetic ordering in NiO changes, leading to a small, measurable coercivity.