Effect of chelating anions on metal-crown interaction. Part III. X-ray structure of potassium picrate complex of benzo-15-crown-5

The cr~¢stal structure of [potassium(benzo-15-crown-5)](picrate) shows that in the complex the metal is sandwiched between two crowns andhas no interaction with plcrate.

X-ray crystal and molecular structure of a hydrated lithium picrate complex of benzo-15-crown-5; An example of non-chelation of the crown

Complexation of alkali and alkaline earth metal ions with crown ethers is well known (1) and chemical and crystallographic studies have been carried out for number of complexes (2,3). The interaction of the metal with the crown ether depends on the nature of the cation and particularly on the basicity of the anion (4) , In this paper we report the crystal and molecular structure of a lithium picrate complex of benzo-15-crown-5, the first x-ray crystallographic study of a lithlum-crown system.

Synthesis and Cytotoxic Evaluation of Novel 2-(4-(2,2,2-Trifluoroethoxy)-3-methylpyridin-2-ylthio)-1H-benzo[d]imid azole Derivatives

The present work deals with the anticancer effect of benzimidazole derivatives associated with the pyridine framework. By varying the functional group at N-terminal of the benzimidazole by different L-amino acids, several 2-(4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-ylthio)-1H-benzo[d]imid azole derivatives 9(a-j) were synthesized. Their chemical structures were confirmed by H-1 NMR, IR and mass spectroscopic techniques. The synthesized compounds were examined for their antiproliferative effects against human leukemia cell lines, K562 and CEM. The preliminary results showed most of the derivatives had moderate antitumor activity. Compound 9j containing cysteine residue exhibited good inhibition compared to other amino acid resides. In addition DNA fragmentation results suggest that 9j is more cytotoxic and able to induce apoptosis.

Conformations of three heterocyclicperhydropyrrolobenzofurans and polymeric assembly via co-operative inter-molecular C-H center dot center dot center dot O hydrogen bonds

In 1-cyclo-hexyl-6,6,8a-trimethyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C19H27NO3, (I), and the isomorphous compounds 6,6,8a-trimethyl-1-phenyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C19H21NO3, (II), and 6,6,8a-trimethyl-1-(3-pyridyl)-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C18H20N2O3, (III), the tetra-hydro-benzo-dihydro-furo-pyrrolidine ring systems are folded at the cis junction of the five-membered rings, giving rise to a non-planar shape of the tricyclic cores. The dihydro-furan and pyrrolidine rings in (I) are puckered and adopt an envelope conformation. The cyclo-hexene rings adopt a half-chair conformation in all the mol-ecules, while the substituent N-cyclo-hexyl ring in (I) assumes a chair form. Short intra-molecular C-HcO contacts form S(5) and S(6) motifs. The isomorphous compounds (II) and (III) are effectively isostructural, and aggregate into chains via inter-molecular C-HcO hydrogen bonds.

Conformations of three heterocyclic perhydropyrrolobenzofurans and polymeric assembly via co-operative inter-molecular C-H center dot center dot center dot O hydrogen bonds

In 1-cyclo-hexyl-6,6,8a-trimethyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro2, 3-b]pyrrole-2,4(3H,5H)-dione, C19H27NO3, (I), and the isomorphous compounds 6,6,8a-trimethyl-1-phenyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro2,3-b]p yrrole-2,4(3H,5H)-dione, C19H21NO3, (II), and 6,6,8a-trimethyl-1-(3-pyridyl)-3a,6,7,8a-tetra-hydro-1H-1-benzofuro2, 3-b]pyrrole-2,4(3H,5H)-dione, C18H20N2O3, (III), the tetra-hydro-benzo-dihydro-furo-pyrrolidine ring systems are folded at the cis junction of the five-membered rings, giving rise to a non-planar shape of the tricyclic cores. The dihydro-furan and pyrrolidine rings in (I) are puckered and adopt an envelope conformation. The cyclo-hexene rings adopt a half-chair conformation in all the mol-ecules, while the substituent N-cyclo-hexyl ring in (I) assumes a chair form. Short intra-molecular C-HcO contacts form S(5) and S(6) motifs. The isomorphous compounds (II) and (III) are effectively isostructural, and aggregate into chains via inter-molecular C-HcO hydrogen bonds.

CXI-benzo-84 reversibly binds to tubulin at colchicine site and induces apoptosis in cancer cells

Here, we have discovered CXI-benzo-84 as a potential anticancer agent from a library of benzimidazole derivatives using cell based screening strategy. CXI-benzo-84 inhibited cell cycle progression in metaphase stage of mitosis and accumulated spindle assembly checkpoint proteins Mad2 and BubR1 on kinetochores, which subsequently activated apoptotic cell death in cancer cells. CXI-benzo-84 depolymerized both interphase and mitotic microtubules, perturbed EB1 binding to microtubules and inhibited the assembly and GTPase activity of tubulin in vitro. CXI-benzo-84 bound to tubulin at a single binding site with a dissociation constant of 1.2 +/- 0.2 mu M. Competition experiments and molecular docking suggested that CXI-benzo-84 binds to tubulin at the colchicine-site. Further, computational analysis provided a significant insight on the binding site of CXI-benzo-84 on tubulin. In addition to its potential use in cancer chemotherapy, CXI-benzo-84 may also be useful to screen colchicine-site agents and to understand the colchicine binding site on tubulin. (C) 2013 Elsevier Inc. All rights reserved.

BT-benzo-29 inhibits bacterial cell proliferation by perturbing FtsZ assembly

We have identified a potent antibacterial agent N-(4-sec-butylphenyl)-2-(thiophen-2-yl)-1H-benzod]imidazole-4-carboxa mide (BT-benzo-29) from a library of benzimidazole derivatives that stalled bacterial division by inhibiting FtsZ assembly. A short (5 min) exposure of BT-benzo-29 disassembled the cytokinetic Z-ring in Bacillus subtilis cells without affecting the cell length and nucleoids. BT-benzo-29 also perturbed the localization of early and late division proteins such as FtsA, ZapA and SepF at the mid-cell. Further, BT-benzo-29 bound to FtsZ with a dissociation constant of 24 +/- 3 m and inhibited the assembly and GTPase activity of purified FtsZ. A docking analysis suggested that BT-benzo-29 may bind to FtsZ at the C-terminal domain near the T7 loop. BT-benzo-29 displayed significantly weaker inhibitory effects on the assembly and GTPase activity of two mutants (L272A and V275A) of FtsZ supporting the prediction of the docking analysis. Further, BT-benzo-29 did not appear to inhibit DNA duplication and nucleoid segregation and it did not perturb the membrane potential of B. subtilis cells. The results suggested that BT-benzo-29 exerts its potent antibacterial activity by inhibiting FtsZ assembly. Interestingly, BT-benzo-29 did not affect the membrane integrity of mammalian red blood cells. BT-benzo-29 bound to tubulin with a much weaker affinity than FtsZ and exerted significantly weaker effects on mammalian cells than on the bacterial cells indicating that the compound may have a strong antibacterial potential.

A New Mechanism For Ferromagnetism In C-60-TDAE

Based on the topology of C-60 and the resulting non-disjoint nature of the lowest unoccupied molecular orbitals, Ne propose a new model for ferromagnetic exchange in C-60-TDAE. Within the Hubbard model, we find that the ferromagnetic exchange integral is stabilized to first order in the inter-ball transfer integral, while the antiferromagnetic coupling is stabilized only to second order. This difference is adequate to counter the larger phase space available for stabilizing the antiferromagnetic state. Thus, the ground state is found to be ferromagnetic for reasonable inter-ball transfer integrals.

A.c. conductivity studies on the silver molybdo-arsenate glassy system

A new quaternary fast-ion conducting silver molybdo-arsenate [Agl-Ag2O-(MoO3 + As2O5)] (SMA) glassy system has been prepared using the melt-quenching technique for various dopant salt (Agl) concentrations by fixing the formers (MoO3 + As2O5) composition and the modifier (Ag2O) to formers (M/F) ratio. The prepared compounds were characterized by X-ray diffraction. The impedance measurements were made on different Agl compositions of the SMA glasses as a function of frequency (6.5 Hz-65 kHz) and temperature (303-343 K), using the Solatron frequency-response analyser(model 1250). The bulk conductivity and the appropriate physical model (equivalent circuit) of the SMA glass were obtained from the impedance analysis. The a.c. conductivity was calculated for different Agl compositions of SMA glasses at various temperatures and the obtained a.c. conductivity results were analysed using Jonscher's Universal Law. The conduction mechanism for the highest conducting SMA glassy compound has been explained using the diffusion path model.

Topological mimicry and epitope duplication in the guanylyl cyclase C receptor

Guanylyl cyclase C (GCC) is the receptor for the gastrointestinal hormones, guanylin, and uroguanylin, in addition to the bacterial heat-stable enterotoxins, which are one of the major causes of watery diarrhea the world over. GCC is expressed in intestinal cells, colorectal tumor tissue and tumors originating from metastasis of the colorectal carcinoma. We have earlier generated a monoclonal antibody to human GCC, GCC:B10, which was useful for the immunohistochemical localization of the receptor in the rat intestine (Nandi A et al., 1997, J Cell Biochem 66:500-511), and identified its epitope to a 63-amino acid stretch in the intracellular domain of GCC. In view of the potential that this antibody has for the identification of colorectal tumors, we have characterized the epitope for GCC:B10 in this study. Overlapping peptide synthesis indicated that the epitope was contained in the sequence HIPPENIFPLE. This sequence was unique to GCC, and despite a short stretch of homology with serum amyloid protein and pertussis toxin, no cross reactivity was detected. The core epitope was delineated using a random hexameric phage display library, and two categories of sequences were identified, containing either a single, or two adjacent proline residues. No sequence identified by phage display was identical to the epitope present in GCC, indicating that phage sequences represented mimotopes of the native epitope. Alignment of these sequences with HIPPENIFPLE suggested duplication of the recognition motif, which was confirmed by peptide synthesis. These studies allowed us not only to define the requirements of epitope recognition by GCC:B10 monoclonal antibody, but also to describe a novel means of epitope recognition involving topological mimicry and probable duplication of the cognate epitope in the native guanylyl cyclase C receptor sequence.

Facile C-O bond scission in alcohols on Zn surfaces

Interaction of methanol, ethanol, and 2-propanol with polycrystalline as well as (0001) surfaces of Zn has been investigated by photoelectron spectroscopy and vibrational energy loss spectroscopy. All the alcohols show evidence for the condensed species along with the chemisorbed species at 80 K. With increase in temperature to similar to 120 K, the condensed species desorbs, leaving the chemisorbed species which decomposes to give the alkoxy species. The alkoxy species is produced increasingly at lower temperatures as we go from methanol to 2-propanol, the 2-propoxy species occurring even at 80 K. The alkoxy species undergo C-O bond scission giving rise to a hydrocarbon species and oxygen. The C-O bond cleavage occurs at a relatively low temperature of similar to 150 K. The effect of preadsorbed oxygen is to stabilize the methoxy species and prevent C-O bond scission. On the other hand, coadsorption of oxygen with methanol favors the formation of the methoxy species and gives rise to hydrocarbon species arising from the C-O bond scission even at 80 K.

Solid state stacked trimers of 1,10-phenanthroline in a supramolecular tubular motif of C-methyl calix[4]resorcinarene

The self-assembly of bidentate ligand, 1,10-phenanthroline with C-methyl calix[4]resorcinarene (CMCR) in presence of coumarin results in a unique trimer stacking arrangement of phenanthroline molecules in a nanotubular motif generated by the supramolecular assembly of the host.

Guanylyl Cyclase C Receptor: Regulation of Catalytic Activity by ATP

Guanylyl cyclase C (GCC), a member of the family of membrane bound guanylyl cyclases is the receptor for the heat-stable enterotoxin (ST) peptides and the guanylin family of endogenous peptides. GCC is activated upon ligand binding to increase intracellular cGMP levels, which in turn activates other downstream signalling events in the cell. GCC is also activated in vitro by nonionic detergents. We have used the T84 cell line as a model system to investigate the regulation of GCC activity by ATP. Ligand-stimulated GCC activity is potentiated in the presence of ATP, whereas detergent-stimulated activity is inhibited. The potentiation of GCC activity by ATP is dependent on the presence of Mg2+ ions, and is probably brought about by a direct binding of Mg-ATP to GCC. The protein kinase-like domain of GCC, which has earlier been shown to play a critical role in the regulation of GCC activity, may be a possible site for the binding of Mg-ATP to GCC.

Highly efficient C-8 oxidation of substituted xanthines with substitution at the 1-, 3-, and 7- positions using biocatalysts

A bacterial consortium consisting of strains belongings to the genus Klebsiella and Rhodococcus quantitatively converts 1-, 3- and 7-substituted xanthines to their respective 8-oxo compounds.

Synthesis of Unnatural C-2 Amino Acid Nucleosides Using NIS-Mediated Ring Opening of 1,2-Cyclopropane Carboxylated Sugar Derivatives

We have developed a general and efficient method for the stereoselective construction of pyrimidine-based pyranosyl C-2 amino acid nucleosides using NIS-mediated ring opening of 1,2-cyclopropanated sugar derivatives. This methodology has been successfully extended to the synthesis of furanosyl nucleosides, Which have potential applications in the development of novel, nontoxic antifungal therapeutics.