Direct Route to Phenol from Benzene

Phenol production, expected to exceed 13MM metric tons in 2017, is a significant global industry with many flaws in its current manufacturing method. The Hock process essentially converts high value propylene to low value acetone. The proposed process design, detailed in this report, provides an alternative reaction pathway that utilizes a direct synthesis from benzene, as developed at the Council of Scientific and Industrial Research (CSIR) in New Delhi, India. The endorsed proposal is in accordance with US Patent 8,772,552 B2, that describes the production of phenol via vapor phase oxidation of benzene over a copper chromium oxide catalyst. Environmental protection and worker safety are paramount concerns due to the hazardous nature of phenol and benzene. The inclusion of a ventilation system with flare hoods keeps the concentration of hazardous materials within OSHA guidelines. The design uses air to oxidize benzene within four separate packed-bed reactors with inter-stage coolers. Downstream separation removes non-condensable species, recycles up to 98% of the unreacted benzene, and purifies phenol to design specifications. The plant’s capacity is 500MM lb/operating-year of phenol and will be located on the U.S. Gulf Coast as part of an industrial complex. The final product is 99.83% phenol by mass, and contains an aldehyde byproduct as the principal impurity. The design requires an initial investment of $83.6MM, yields a fifteen-year net present value (NPV) of$90M, and has an estimated investor’s rate of return (IRR) of 29.2%. The proposed project is forecasted to break-even in Q1 of 2025 immediately following the second year of maximum production capacity. The design is recommended based on project specifications and marketing team projections, though investors should exercise caution with regards to the effect of realistic market data on proposal sensitivities

An Energy and Performance Exploration of Network-on-Chip Architectures

In this paper, we explore the designs of a circuit-switched router, a wormhole router, a quality-of-service (QoS) supporting virtual channel router and a speculative virtual channel router and accurately evaluate the energy-performance tradeoffs they offer. Power results from the designs placed and routed in a 90-nm CMOS process show that all the architectures dissipate significant idle state power. The additional energy required to route a packet through the router is then shown to be dominated by the data path. This leads to the key result that, if this trend continues, the use of more elaborate control can be justified and will not be immediately limited by the energy budget. A performance analysis also shows that dynamic resource allocation leads to the lowest network latencies, while static allocation may be used to meet QoS goals. Combining the power and performance figures then allows an energy-latency product to be calculated to judge the efficiency of each of the networks. The speculative virtual channel router was shown to have a very similar efficiency to the wormhole router, while providing a better performance, supporting its use for general purpose designs. Finally, area metrics are also presented to allow a comparison of implementation costs

Estimating Protein-Ligand Binding Affinity using High- Throughput Screening by NMR

Many of today’s drug discovery programs utilize high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or linewidth to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR-based screens that use 1D 1H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA

Estimating Protein-Ligand Binding Affinity using High- Throughput Screening by NMR

Many of today’s drug discovery programs utilize high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or linewidth to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR-based screens that use 1D 1H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA

Anodic deposition of a robust iridium-based water-oxidation catalyst from organometallic precursors

Artificial photosynthesis, modeled on natural light-driven oxidation of water in Photosystem II, holds promise as a sustainable source of reducing equivalents for producing fuels. Few robust water-oxidation catalysts capable of mediating this difficult four-electron, four-proton reaction have yet been described. We report a new method for generating an amorphous electrodeposited material, principally consisting of iridium and oxygen, which is a robust and long-lived catalyst for water oxidation, when driven electrochemically. The catalyst material is generated by a simple anodic deposition from Cp*Ir aqua or hydroxo complexes in aqueous solution. This work suggests that organometallic precursors may be useful in electrodeposition of inorganic heterogeneous catalysts

Replacing the Z-phenyl Ring in Tamoxifen® with a para-Connected NCN Pincer-Pt-Cl Grouping by Post-Modification

Post-modification of a series of NCN-pincer platinum(II) complexes [PtX(NCN-R-4)] (NCN = [C6H2(CH2NMe2)2-2,6]–, R = C(O)H, C(O)Me and C(O)Et), X = Cl– or Br–) at the para-position using the McMurry reaction was studied. The synthetic route towards two new [PtCl(NCN-R-4)] (R = C(O)Me and C(O)Et) complexes used above is likewise described. The utility and limitations of the McMurry reaction involving these pincer complexes was systematically evaluated. The predicted “homo-coupling” reaction of [PtBr(NCN-C(O)H-4)] led to the unexpected formation of 3,3′,5,5′-tetra[(dimethylamino)methyl]-4,4′-bis(platinum halide)-benzophenone (halide = Br or Cl), referred to hereafter as the bispincer-benzophenone complex 13. This material was further characterized using X-ray crystal structure determination. The applicability of the pincer complexes in the McMurry reaction is shown to open a route towards the synthesis of tamoxifen-type derivatives of which one phenyl ring of Tamoxifen® itself is replaced by an NCN arylplatinum pincer fragment. The newly synthesized derivatives can be used as potential candidates in anti-cancer drug screening protocols. Two NCN-arylpincer platinum tamoxifen type derivatives, 5 and 6, were successfully synthesized and of 5 the separation of the diastereomeric E-/Z-forms was achieved. Compound 6, which is the pivaloyl protected NCN pincer platinum hydroxy-Tamoxifen® derivative, was obtained as a mixture of E-/Z-isomers. The new derivatives were further analyzed and characterized with 1H-, 13C{1H}- and 195Pt{1H}-NMR, IR, exact mass MS and elemental analysis.This research was partly funded by the Council for Chemical Sciences of the Netherlands Organization for Scientific Research (NWO/CW) G.D.B., M.L

Anomalies in low-energy Gamma-Ray Burst spectra with the Fermi Gamma-Ray Burst Monitor

A Band function has become the standard spectral function used to describe the prompt emission spectra of gamma-ray bursts (GRBs). However, deviations from this function have previously been observed in GRBs detected by BATSE and in individual GRBs from the \textit{Fermi} era. We present a systematic and rigorous search for spectral deviations from a Band function at low energies in a sample of the first two years of high fluence, long bursts detected by the \textit{Fermi} Gamma-Ray Burst Monitor (GBM). The sample contains 45 bursts with a fluence greater than 2$\times10^{-5}$ erg / cm$^{2}$ (10 - 1000 keV). An extrapolated fit method is used to search for low-energy spectral anomalies, whereby a Band function is fit above a variable low-energy threshold and then the best fit function is extrapolated to lower energy data. Deviations are quantified by examining residuals derived from the extrapolated function and the data and their significance is determined via comprehensive simulations which account for the instrument response. This method was employed for both time-integrated burst spectra and time-resolved bins defined by a signal to noise ratio of 25 $\sigma$ and 50 $\sigma$. Significant deviations are evident in 3 bursts (GRB\,081215A, GRB\,090424 and GRB\,090902B) in the time-integrated sample ($\sim$ 7%) and 5 bursts (GRB\,090323, GRB\,090424, GRB\,090820, GRB\,090902B and GRB\,090926A) in the time-resolved sample ($\sim$ 11%).} The advantage of the systematic, blind search analysis is that it can demonstrate the requirement for an additional spectral component without any prior knowledge of the nature of that extra component. Deviations are found in a large fraction of high fluence GRBs; fainter GRBs may not have sufficient statistics for deviations to be found using this method

FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorption

Bile acid malabsorption, which in patients leads to excessive fecal bile acid excretion and diarrhea, is characterized by a vicious cycle in which the feedback regulation of bile acid synthesis is interrupted, resulting in additional bile acid production. Feedback regulation of bile acid synthesis is under the control of an endocrine pathway wherein activation of the nuclear bile acid receptor, farnesoid X receptor (FXR), induces enteric expression of the hormone, fibroblast growth factor 15 (FGF15). In liver, FGF15 acts together with FXR-mediated expression of small heterodimer partner to repress bile acid synthesis. Here, we show that the FXR-FGF15 pathway is disrupted in mice lacking apical ileal bile acid transporter, a model of bile acid malabsorption. Treatment of Asbt-/- mice with either a synthetic FXR agonist or FGF15 downregulates hepatic cholesterol 7alpha-hydroxylase mRNA levels, decreases bile acid pool size, and reduces fecal bile acid excretion. These findings suggest that FXR agonists or FGF15 could be used therapeutically to interrupt the cycle of excessive bile acid production in patients with bile acid malabsorption