Designing Ternary Co-crystals with Stacking Interactions and Weak Hydrogen Bonds. 4,4 `-Bis-hydroxyazobenzene

Three ternary co-crystals of the title compound are reported. The design strategy hinges on the identification of a robust synthon with O-H center dot center dot center dot N hydrogen bonds in a binary co-crystal. Construction of this module allows the tuning of pi center dot center dot center dot pi stacking interactions and weak hydrogen bonds to incorporate the third component into the crystal structure. Screening of various co-formers showed that a delicate balance of electrostatics is required for stacking to favor the formation of ternaries. A C-H center dot center dot center dot N hydrogen-bonded motif was also found to occur repetitively in the ternary co-crystals. The directional nature of weak hydrogen bonds allows them to be used effectively in this study.

New 4-(2-(4-alkoxyphenyl)-6-methoxypyridin-4-yl) benzonitriles: synthesis, liquid crystalline behavior and photo physical properties

A new series of luminescent 4-(2-(4-alkoxyphenyl)-6-methoxypyridin-4-yl) benzonitriles containing three ring systems, viz. methoxy pyridine, benzonitrile and alkoxy benzene with variable alkoxy chain length, with bent-core structures were synthesized as potential mesogens and characterized by spectral techniques. Their liquid crystalline behavior was investigated by polarizing optical microscopy (POM), differential scanning calorimetry (DSC) and variable temperature powder X-ray diffraction (PXRD) measurements. The study reveals that compounds with shorter chain lengths i.e. m = 4] exclusively exhibit the nematic phase while compounds with longer chain lengths i.e. m = 6-14 (only even)] show predominantly the orthorhombic columnar phase. Single crystal X-ray analysis of 4-(2-(4-butyloxy/octyloxyphenyl)-6-methoxypyridin-4-yl) benzonitriles reveals that they possess slightly non-planar unsymmetrical bent structures and their molecular packing consists of nonconventional H-bond interactions; it also explains the observed liquid crystalline phase. An optical study indicates that the title compounds are good blue emitting materials showing absorption and emission bands in the range 335-345 nm and 415-460 nm, respectively. An electrochemical study of 4-(2-(4-octyloxyphenyl)-6-methoxypyridin-4-yl) benzonitrile shows a band gap of 1.89 eV with HOMO and LUMO energy levels of -5.06 and -3.17 eV, respectively. Also, density functional theory (DFT) calculations confirm its optimized geometry, electronic absorption and frontier molecular orbital distributions.

Specroelectrochemical, Switching Kinetics, and Chronoamperometric Studies of Dibenzyl Derivative of Poly(3,4-propylenedioxythiophene) Thin-Film-Based Electrochromic Device

The dibenzyl derivative of poly(3,4-propylenedioxythiophene) (PProDOT-Bz(2)) thin film is deposited onto ITO-coated glass substrate by electropolymerization technique. The electropolymerization of ProDOT-Bz(2) is carried out by a three-electrode electrochemical cell. The cyclic voltammogram shows the redox properties of electrochemically prepared films deposited at different scan rates. The thin films prepared were characterized for its morphological properties to study the homogeniety. Classic six-layer structure of PProDOT-Bz(2) electrochromic device using this material was fabricated and reported for the first and its characterizations such as spectroelectrochemical, switching kinetics, and chronoamperometric studies are performed. The color contrast of the thin film and the device achieved are 64 and 40%, respectively, at lambda(max) (628 nm). The switching time is recorded and the observed values are 5 s from the coloring state to the bleaching state and vice versa. The chronoamperometry shows that the device performed up to 400 cycles, and it is capable of working up to 35 cycles without any degradation. (C) 2014 Wiley Periodicals, Inc.

Synthesis and antiproliferative effect of novel 4-thiazolidinone-, pyridine- and piperazine-based conjugates on human leukemic cells

The present work reveals the synthesis and antiproliferative effect of a series of 2, 3 disubstituted 4-thiazolidinone analogues on human leukemic cells. The chemical structures of newly synthesized compounds were confirmed by IR, H-1 NMR, C-13 NMR and mass spectral analysis. Compound methyl 3-methoxy-4-(4-oxo-3-(5-(piperazin-1-yl)pyridin-2-yl)thiazolidin-2-yl)be nzoate (5) displayed potent activity (IC50 9.71, 15.24 and 19.29 mu M) against Nalm6, K562, Jurkat cells. Cell cycle analysis and mitochondrial membrane potential further confirmed that compound 5 is cytotoxic and able to induce cell death. (C) 2014 Elsevier Masson SAS. All rights reserved.

STAT-1 expression is regulated by IGFBP-3 in malignant glioma cells and is a strong predictor of poor survival in patients with glioblastoma Laboratory investigation

Object. Insulin-like growth factor binding proteins (IGEBPs) have been implicated in the pathogenesis of glioma. In a previous study the authors demonstrated that IGFBP-3 is a novel glioblastoma biomarker associated with poor survival. Since signal transducer and activator of transcription 1 (STAT-1) has been shown to be regulated by IGFBP-3 during chondrogenesis and is a prosurvival and radioresistant molecule in different tumors, the aim in the present study was to explore the functional significance of IGFBP-3 in malignant glioma cells, to determine if STAT-1 is indeed regulated by IGFBP-3, and to study the potential of STAT-1 as a biomarker in glioblastoma. Methods. The functional significance of IGFBP-3 was investigated using the short hairpin (sh)RNA gene knockdown approach on U251MG cells. STAT-1 regulation by IGFBP-3 was tested on U251MG and U87MG cells by shRNA gene knockdown and exogenous treatment with recombinant IGFBP-3 protein. Subsequently, the expression of STAT-1 was analyzed with real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) in glioblastoma and control brain tissues. Survival analyses were done on a uniformly treated prospective cohort of adults with newly diagnosed glioblastoma (136 patients) using Kaplan-Meier and Cox regression models. Results. IGFBP-3 knockdown significantly impaired proliferation, motility, migration, and invasive capacity of U251MG cells in vitro (p < 0.005). Exogenous overexpression of IGFBP-3 in U251MG and U87MG cells demonstrated STAT-1 regulation. The mean transcript levels (by real-time RT-PCR) and the mean labeling index of STAT-1 (by IHC) were significantly higher in glioblastoma than in control brain tissues (p = 0.0239 and p < 0.001, respectively). Multivariate survival analysis revealed that STAT-1 protein expression (HR 1.015, p = 0.033, 95% CI 1.001-1.029) along with patient age (HR 1.025, p = 0.005, 95% CI 1.008-1.042) were significant predictors of shorter survival in patients with glioblastoma. Conclusions. IGFBP-3 influences tumor cell proliferation, migration, and invasion and regulates STAT-1 expression in malignant glioma cells. STAT-1 is overexpressed in human glioblastoma tissues and emerges as a novel prognostic biomarker.

Role of the loop L-4,L-5 in allosteric regulation in mtHsp70s: in vivo significance of domain communication and its implications in protein translocation

Mitochondrial Hsp70 (mtHsp70) is essential for a vast repertoire of functions, including protein import, and requires effective interdomain communication for efficient partner-protein interactions. However, the in vivo functional significance of allosteric regulation in eukaryotes is poorly defined. Using integrated biochemical and yeast genetic approaches, we provide compelling evidence that a conserved substrate-binding domain (SBD) loop, L-4,L-5, plays a critical role in allosteric communication governing mtHsp70 chaperone functions across species. In yeast, a temperature-sensitive L-4,L-5 mutation (E467A) disrupts bidirectional domain communication, leading to compromised protein import and mitochondrial function. Loop L-4,L-5 functions synergistically with the linker in modulating the allosteric interface and conformational transitions between SBD and the nucleotide-binding domain (NBD), thus regulating interdomain communication. Second-site intragenic suppressors of E467A isolated within the SBD suppress domain communication defects by conformationally altering the allosteric interface, thereby restoring import and growth phenotypes. Strikingly, the suppressor mutations highlight that restoration of communication from NBD to SBD alone is the minimum essential requirement for effective in vivo function when primed at higher basal ATPase activity, mimicking the J-protein-bound state. Together these findings provide the first mechanistic insights into critical regions within the SBD of mtHsp70s regulating interdomain communication, thus highlighting its importance in protein translocation and mitochondrial biogenesis.

Serum proteomics of hepatitis C virus infection reveals retinol-binding protein 4 as a novel regulator

Persistent infection of hepatitis C virus (HCV) can lead to liver cirrhosis and hepatocellular carcinoma, which are currently diagnosed by invasive liver biopsy. Approximately 15-20% of cases of chronic liver diseases in India are caused by HCV infection. In North India, genotype 3 is predominant, whereas genotype 1 is predominant in southern parts of India. The aim of this study was to identify differentially regulated serum proteins in HCV-infected Indian patients (genotypes 1 and 3) using a two-dimensional electrophoresis approach. We identified eight differentially expressed proteins by MS. Expression levels of one of the highly upregulated proteins, retinol-binding protein 4 (RBP4), was validated by ELISA and Western blotting in two independent cohorts. We also confirmed our observation in the JFH1 infectious cell culture system. Interestingly, the HCV core protein enhanced RBP4 levels and partial knockdown of RBP4 had a positive impact on HCV replication, suggesting a possible role for this cellular protein in regulating HCV infection. Analysis of RBP4-interacting partners using a bioinformatic approach revealed novel insights into the possible involvement of RBP4 in HCV-induced pathogenesis. Taken together, this study provided information on the proteome profile of the HCV-infected Indian population, and revealed a link between HCV infection, RBP4 and insulin resistance.