B-H Bond Activation Using an Electrophilic Metal Complex: Insights into the Reaction Pathway

A highly electrophilic ruthenium center in the RuCl(dppe)(2)]OTf] complex brings about the activation of the B H bond in ammonia borane (H3N center dot BH3, AB) and dimethylamine borane (Me2HN center dot BH3, DMAB). At room temperature, the reaction between RuCl(dppe)(2)]OTf] and AB or DMAB results in trans-RuH(eta(2)-H-2)(dppe)(2)]OTf] trans-RuCl(eta(2)-H-2)(dppe)(2)]OTf], and trans-RuH(Cl)(dppe)(2)], as noted in the NMR spectra. Mixing the ruthenium complex and AB or DMAB at low temperature (198/193 K) followed by NMR spectral measurements as the reaction mixture was warmed up to room temperature allowed the observation of various species formed enroute to the final products that were obtained at room temperature. On the basis of the variable-temperature multinuclear NMR spectroscopic studies of these two reactions, the mechanistic insights for B-H bond activation were obtained. In both cases, the reaction proceeds via an eta(1)-B-H moiety bound to the metal center. The detailed mechanistic pathways of these two reactions as studied by NMR spectroscopy are described.

Effect of Metal Ions (Ag, Co, Ni, and Pd) on the Visible Light Degradation of Rhodamine B by Carbon-Covered Alumina-Supported TiO2 in Aqueous Solutions

Metal-ion (Ag, Co, Ni, and Pd) doped TiO2 nanocatalysts were successfully embedded on carbon-covered alumina supports. The CCA-embedded catalysts were crystalline and had a high surface area compared to the free metal-ion doped titania nanocatalysts while they still retained the anatase phase of the core TiO2. These catalysts were photocatalytically active under solar light irradiation. Rhodamine B was used as a model pollutant and the reactivity followed a pseudo-first-order reaction kinetics. The reaction rate of the CCA-supported catalysts was Pd > Ag > Co > Ni. Among the ratios of the CCA:catalyst used, it was found that the 1:1 ratio had the fastest reaction rate, followed by the 1:2 ratio, while the 2:1 ratio exhibited the lowest reaction rate. The CCA/metal-ion doped titania were found to have photocatalytic activities comparable with those of CCA-supported titania.

Total synthesis and determination of the absolute configuration of 5,6-Dihydro-alpha-pyrone natural product synargentolide B

Enantiospecific total synthesis and determination of the absolute stereochemistry of the alpha-pyrone-containing natural product synargentolide B were accomplished. The absolute stereochemistry of the natural product was established by synthesizing the possible diastereomers and comparison of the data with those reported for the natural product. During the process, total synthesis of the putative structure of related natural product 6R-1S,2R,SR,6S-(tetraacetyloxy)-3E-heptenyl]-5,6-dihydro-2H-pyran-2-o ne was also accomplished and confirmed by X-ray crystal structure analysis. Wittig-Horner reaction of a chiral phosphonate derived from (S)-lactic acid and ring-closing metathesis were the key reactions during the course of the total synthesis.

A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent.

Reactive hot pressing of Ti-B-C and Ti-C at 1200 degrees C

Stoichiometric and non-stoichiometric powder mixtures of Ti-B4C and Ti-C with 1 wt% Ni were reactively hot pressed at 40 MPa, 1200 degrees C for 30 min. In both systems, the combined presence of Ni and non-stoichiometry enabled complete densification. While in Ti-C, non-stoichiometry by itself plays a significant role in promoting densification, the formation of intermediate borides in Ti-B4C powder mixtures requires the additional presence of Ni which promotes full reaction through the formation of a transient liquid as established previously in Ti-BN powder mixtures.

Processing of enriched elemental boron (B-10 similar to 65 at. %)

Procedures were developed for purification and processing of electrodeposited enriched boron powder for control rod application in India's first commercial Proto Type Fast Breeder Reactor (PFBR). Methodology for removal of anionic (F-, Cl-, BF4-) and cationic (Fe2+, Fe3+, Ni2+) impurities was developed. Parameters for grinding boron flakes obtained after electrodeposition were optimized to obtain the boron powder having particle size less than 100 gm. The rate of removal of impurities was studied with respect to time and concentration of the reagents used for purification. Process parameters for grinding and removal of impurities were optimized. A flowsheet was proposed which helps in minimizing the purification time and concentration of the reagent used for the effective removal of impurities. The purification methodology developed in this work could produce boron that meets the technical specifications for control rod application in a fast reactor.

Effect of hydrogen charging on tensile properties of B-modified Ti-6Al-4V alloy

Trace addition of B to Ti and its alloys leads to a marked microstructural refinement, which in turn enhances the tensile and fatigue properties of the as-cast alloys. This can be particularly advantageous in applications wherein Ti alloys are used in the as-cast form. In some of these, the environment containing H and Ti alloy components is susceptible to embrittlement due to H uptake. Whether the addition of B to Ti-6Al-4V improves the relative mechanical performance of such cast components used in H environments is examined in this work. Cast Ti-6Al-4V-xB (0 <= x <= 0.55 wt%) alloys were H charged at 500 and 700 degrees C for up to 4 h. Microstructures and room temperature tensile properties of the resulting alloys have been evaluated. Experimental results show that charging at 700 degrees C for 2 h leads to the formation of titanium hydride in the microstructure, which in turn causes severe embrittlement. For shorter durations of charging, a marginal increase in strength was noted, which is attributed to the solid solution strengthening by H. The mechanical performance of the B modified alloys was found to be relatively higher, implying that B addition not only refines the as-cast microstructure but also is beneficial in applications that involve H environment A direct correlation between the volume fraction of TiB particles in the microstructure and the relative reduction in the strength of H-embrittled alloys suggests that the addition of B to Ti alloys, in optimum quantities, can be utilized as a strategy to design alloys that are more resistant to H embrittlement.

Metal doped nanosized titania used for the photocatalytic degradation of rhodamine B dye under visible-light

Metal-doped anatase nanosized titania photocatalysts were successfully synthesized using a sal gel process. Different amounts of the dopants (0.2, 0.4, 0.6, 0.8 and 1.0%) of the metals (Ag, Ni, Co and Pd) were utilized. The UV-Vis spectra (solid state diffuse reflectance spectra) of the doped nanoparticles exhibited a red shift in the absorption edge as a result of metal doping. The metal-doped nanoparticles were investigated for their photocatalytic activity under visible-light irradiation using Rhodamine B (Rh B) as a control pollutant. The results obtained indicate that the metal-doped titania had the highest activity at 0.4% metal loading. The kinetic models revealed that the photodegradation of Rh B followed a pseudo first order reaction. From ion chromatography (IC) analysis the degradation by-products Rhodamine B fragments were found to be acetate, chloride, nitrite, carbonate and nitrate ions.

A Novel Anticancer Agent, 8-Methoxypyrimido4 `,5 `: 4,5]thieno(2,3-b) Quinoline-4(3H)-One Induces Neuro 2a Neuroblastoma Cell Death through p53-Dependent, Caspase-Dependent and Independent Apoptotic Pathways

Neuroblastoma is the most common cancer in infants and fourth most common cancer in children. Despite recent advances in cancer treatments, the prognosis of stage-IV neuroblastoma patients continues to be dismal which warrant new pharmacotherapy. A novel tetracyclic condensed quinoline compound, 8-methoxypyrimido 4 `,5 `: 4,5] thieno(2,3-b) quinoline-4(3H)-one (MPTQ) is a structural analogue of an anticancer drug ellipticine and has been reported to posses anticancer property. Study on MPTQ on neuroblastoma cells is very limited and mechanisms related to its cytotoxicity on neuroblastoma cells are completely unknown. Here, we evaluated the anticancer property of MPTQ on mouse neuro 2a and human SH-SY5Y neuroblastoma cells and investigated the mechanisms underlying MPTQ-mediated neuro 2a cell death. MPTQ-mediated neuro 2a and SH-SY5Y cell deaths were found to be dose and time dependent. Moreover, MPTQ induced cell death reached approximately 99.8% and 90% in neuro 2a and SH-SY5Y cells respectively. Nuclear oligonucleosomal DNA fragmentation and Terminal dUTP Nick End Labelling assays indicated MPTQ-mediated neuro 2a cell death involved apoptosis. MPTQ-mediated apoptosis is associated with increased phosphorylation of p53 at Ser15 and Ser20 which correlates with the hyperphosphorylation of Ataxia-Telangiectasia mutated protein (ATM). Immunocytochemical analysis demonstrated the increased level of Bax protein in MPTQ treated neuro 2a cells. MPTQ-mediated apoptosis is also associated with increased activation of caspase-9, -3 and -7 but not caspase-2 and -8. Furthermore, increased level of caspase-3 and cleaved Poly ( ADP Ribose) polymerase were observed in the nucleus of MPTQ treated neuro 2a cells, suggesting the involvement of caspase-dependent intrinsic but not extrinsic apoptotic pathway. Increased nuclear translocation of apoptosis inducing factor suggests additional involvement of caspase-independent apoptosis pathway in MPTQ treated neuro 2a cells. Collectively, MPTQ-induced neuro 2a cell death is mediated by ATM and p53 activation, and Bax-mediated activation of caspase-dependent and caspase-independent mitochondrial apoptosis pathways.

Strain-controlled fatigue in B-modified Ti-6Al-4V alloys

The strain-controlled fatigue behaviour of Ti-6Al-4V alloy with up to 0.11 wt.% B addition was investigated. Results show significant softening when the strain amplitudes, Delta epsilon(T)/2, are >= 0.75%. B addition was found to improve the fatigue life for Delta epsilon(T)/2 <= 0.75% as it corresponds to the elastic regime and hence is strength dominated. At Delta epsilon(T)/2 = 1%, in contrast, the base alloy exhibits higher fatigue life as TiB particle cracking due to strain incompatibility causes easy crack nucleation in the B-modified alloys. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Detection of Hepatitis B DNA Sequences on Polyelectrolyte Based Non-Covalently Functionalized Flexible Plastic Substrates

Development of simple functionalization methods to attach biomolecules such as proteins and DNA on inexpensive substrates is important for widespread use of low cost, disposable biosensors. Here, we describe a method based on polyelectrolyte multilayers to attach single stranded DNA molecules to conventional glass slides as well as a completely non-standard substrate, namely flexible plastic transparency sheets. We then use the functionalized transparency sheets to specifically detect single stranded Hepatitis B DNA sequences from samples. We also demonstrate a blocking method for reducing non-specific binding of target DNA sequences using negatively charged polyelectrolyte molecules. The polyelectrolyte based functionalization method, which relies on surface charge as opposed to covalent surface linkages, could be an attractive platform to develop assays on inexpensive substrates for low cost biosensing.

A DNA methylation prognostic signature of glioblastoma: identification of NPTX2-PTEN-NF-kappa B nexus

Glioblastoma (GBM) is the most common, malignant adult primary tumor with dismal patient survival, yet the molecular determinants of patient survival are poorly characterized. Global methylation profile of GBM samples (our cohort; n = 44) using high-resolution methylation microarrays was carried out. Cox regression analysis identified a 9-gene methylation signature that predicted survival in GBM patients. A risk-score derived from methylation signature predicted survival in univariate analysis in our and The Cancer Genome Atlas (TCGA) cohort. Multivariate analysis identified methylation risk score as an independent survival predictor in TCGA cohort. Methylation risk score stratified the patients into low-risk and high-risk groups with significant survival difference. Network analysis revealed an activated NF-kappa B pathway association with high-risk group. NF-kappa B inhibition reversed glioma chemoresistance, and RNA interference studies identified interleukin-6 and intercellular adhesion molecule-1 as key NF-kappa B targets in imparting chemoresistance. Promoter hypermethylation of neuronal pentraxin II (NPTX2), a risky methylated gene, was confirmed by bisulfite sequencing in GBMs. GBMs and glioma cell lines had low levels of NPTX2 transcripts, which could be reversed upon methylation inhibitor treatment. NPTX2 overexpression induced apoptosis, inhibited proliferation and anchorage-independent growth, and rendered glioma cells chemosensitive. Furthermore, NPTX2 repressed NF-kappa B activity by inhibiting AKT through a p53-PTEN-dependent pathway, thus explaining the hypermethylation and downregulation of NPTX2 in NF-kappa B-activated high-risk GBMs. Taken together, a 9-gene methylation signature was identified as an independent GBM prognosticator and could be used for GBM risk stratification. Prosurvival NF-kappa B pathway activation characterized high-risk patients with poor prognosis, indicating it to be a therapeutic target. (C) 2013 AACR.

Methionine down-regulates TLR4/MyD88/NF-kappa B signalling in osteoclast precursors to reduce bone loss during osteoporosis

Background and PurposeStudies have demonstrated that a moderate intake of amino acids is associated with development of bone health. Methionine, a sulphur-containing essential amino acid, has been largely implicated for improving cartilage formation, however its physiological significance on bone integrity and functionality have not been elucidated. We investigated whether methionine can prevent osteoporotic bone loss. Experimental ApproachThe anti-resorptive effect of methionine, (250mgkg(-1) body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized (OVX) rats by monitoring changes in bone turnover, formation of osteoclasts from blood-derived mononuclear cells and changes in the synthesis of pro-osteoclastogenic cytokines. Key resultsMethionine improved bone density and significantly decreased the degree of osteoclast development from blood mononuclear cells in OVX rats, as indicated by decreased production of osteoclast markers tartarate resistant acid phosphatase b (TRAP5b) and MIP-1. siRNA-mediated knockdown of myeloid differentiation primary response 88 MyD88], a signalling molecule in the toll-like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP-1 in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR-4/MyD88/NF-B pathway. Conclusions and ImplicationsTLR-4/MyD88/NF-B signalling pathway is integral for osteoclast development and this is down-regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis.

Quantum chemical study on influence of intermolecular hydrogen bonding on the geometry, the atomic charges and the vibrational dynamics of 2,6-dichlorobenzonitrile

FT-IR (4000-400 cm(-1)) and FT-Raman (4000-200 cm(-1)) spectral measurements on solid 2,6-dichlorobenzonitrile (2,6-DCBN) have been done. The molecular geometry, harmonic vibrational frequencies and bonding features in the ground state have been calculated by density functional theory at the B3LYP/6-311++G (d,p) level. A comparison between the calculated and the experimental results covering the molecular structure has been made. The assignments of the fundamental vibrational modes have been done on the basis of the potential energy distribution (PED). To investigate the influence of intermolecular hydrogen bonding on the geometry, the charge distribution and the vibrational spectrum of 2,6-DCBN; calculations have been done for the monomer as well as the tetramer. The intermolecular interaction energies corrected for basis set superposition error (BSSE) have been calculated using counterpoise method. Based on these results, the correlations between the vibrational modes and the structure of the tetramer have been discussed. Molecular electrostatic potential (MEP) contour map has been plotted in order to predict how different geometries could interact. The Natural Bond Orbital (NBO) analysis has been done for the chemical interpretation of hyperconjugative interactions and electron density transfer between occupied (bonding or lone pair) orbitals to unoccupied (antibonding or Rydberg) orbitals. UV spectrum was measured in methanol solution. The energies and oscillator strengths were calculated by Time Dependent Density Functional Theory (TD-DFT) and matched to the experimental findings. TD-DFT method has also been used for theoretically studying the hydrogen bonding dynamics by monitoring the spectral shifts of some characteristic vibrational modes involved in the formation of hydrogen bonds in the ground and the first excited state. The C-13 nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the Gauge independent atomic orbital (GIAO) method and compared with experimental results. Standard thermodynamic functions have been obtained and changes in thermodynamic properties on going from monomer to tetramer have been presented. (C) 2013 Elsevier B.V. All rights reserved.

Large linear magnetoresistance in a GaAs/AlGaAs heterostructure

We report non-saturating linear magnetoresistance (MR) in a two-dimensional electron system (2DES) at a GaAs/AlGaAs heterointerface in the strongly insulating regime. We achieve this by driving the gate voltage below the pinch-off point of the device and operating it in the non-equilibrium regime with high source-drain bias. Remarkably, the magnitude of MR is as large as 500% per Tesla with respect to resistance at zero magnetic field, thus dwarfing most non-magnetic materials which exhibit this linearity. Its primary advantage over most other materials is that both linearity and the enormous magnitude are retained over a broad temperature range (0.3 K to 10 K), thus making it an attractive candidate for cryogenic sensor applications.