A New Lead Identification Strategy: Screening an sp3-rich and Lead-like Compound Library Composed of 7-Azanorbornane Derivatives

Although the advantages of sp³-rich, sterically complicated molecules in drug development have been pointed out, modern screening libraries are filled with planar, sp²-rich components. Compounds that are sp³-rich are difficult to synthesize, and thus we aimed to invent an efficient method to construct sp³-rich libraries. By modifying sp³-rich 7-azanorbornane scaffolds through click chemistry, we efficiently prepared a small set of compounds. These compounds were not only sp³-rich, but also had sufficient “lead-like” properties in view of molecular weights and hydrophobicity. Screening assays of this library provided weak κ opioid receptor agonists and growth hormone secretagogue receptor agonists with high hit rates. These results indicate that the 7-azanorbornane scaffold may be a “privileged structure” for lead identification in drug discovery.     

Reusable Floating Beads with Immobilized Xylose-Fermenting Yeast Cells for Simultaneous Saccharification and Fermentation of Lime-Pretreated Rice Straw

Novel bioreactor beads for simultaneous saccharification and fermentation (SSF) of lime-pretreated rice straw (RS) into ethanol were prepared. Genetically modified Saccharomyces cerevisiae cells expressing genes encoding xylose reductase, xylitol dehydrogenase, and xylulokinase were immobilized in calcium alginate beads containing inorganic lightweight filler particles to reduce specific gravity. For SSF experiments, the beads were floated in slurry composed of lime-pretreated RS and enzymes and incubated under CO₂ atmosphere to reduce the pH for saccharification and fermentation. Following this reaction, beads were readily picked up from the upper part of the slurry and were directly transferred to the next vessel with slurry. After 240 h of incubation, ethanol production by the beads was equivalent to that by free cells, a trend that was repeated in nine additional runs, with slightly improved ethanol yields. Slurry with pre-saccharified lime-pretreated RS was subjected to SSF with floating beads for 168 h. Although higher cell concentrations in beads resulted in more rapid initial ethanol production rates, with negligible diauxic behavior for glucose and xylose utilization, no improvement in the ethanol yield was observed. A fermentor-scale SSF experiment with floating beads was successfully performed twice, with repeated use of the beads, resulting in the production of 40.0 and 39.7 g/L ethanol. There was no decomposition of the beads during agitation at 60 rpm. Thus, this bioreactor enables reuse of yeast cells for efficient ethanol production by SSF of lignocellulosic feedstock, without the need for instruments for centrifugation or filtration of whole slurry.     

Solution properties of mixed surfactant system sodium dodecyl sulfate and alkyl polyoxyethylene ether system

The effect of oxyethylene groups in a nonionic surfactant on the solution properties of anionicnonionic systems is described; these systems are sodium dodecyl sulfate (SDS)—hexadecyl polyoxyethylene ethers (C₁₆POE_n, where n=10, 20, 30 and 40). The degree of ionic dissociation of the mixed micelles decreases with increasing numbers of oxyethylene groups in the nonionic surfactant. As polyoxyethylene chain lengths increase, the electrical conductivities of the mixed surfactant solutions decrease, in spite of the decrease in activation energy for conduction. The radius of the mixed micelle with the electric double layer is larger for a nonionic surfactant having a shorter polyoxyethylene chain length than for one having a long polyoxyethylene chain. This may be attributed to the fact that the mixed micelle is formed more easily by a nonionic surfactant with a shorter polyoxyethylene chain length than by one with a longer chain.     

Narrow multi-walled carbon nanotubes produced by chemical vapor deposition using graphene layer encapsulated catalytic metal particles

The use of graphene layer encapsulated catalytic metal particles for the growth of narrower multi-walled carbon nanotubes (MWCNTs) has been studied using plasma-enhanced chemical vapor deposition and conventional thermal CVD. Ni–C or Fe–C composite nanoclusters were fabricated using the dc arc discharge technique with metal–graphite composite electrodes carrying a current of 100–200 A in a stainless-steel chamber filled with He and CH₄ mixture gas at 27 kPa. Nano-sized grains with diameters less than 10 nm were fabricated and deposited on a Si substrate, and were used as a catalyst for MWCNT growth. Structural analyses of the composite nanoclusters and MWCNTs were carried out using transmission electron microscopy. The results show that the diameters of the MWCNTs were reduced from 50–100 nm for a conventional Ni thin film-evaporated Si substrate to a minimum of roughly 2–4 nm in the present study.     

Incorporation of benzothiadiazole moiety at junction of polyfluorene–polytriarylamime block copolymer for effective color tuning in organic light emitting diode

Block copolymer consisting of polyfluorene and polytriarylamine with benzothiadiazole moiety at the junction is prepared in order to obtain an orange emitting polymer via Suzuki‐Miyaura followed by Buchwald‐Hartwig coupling reactions. Electroluminescent device fabricated with resulting block copolymer exhibit only orange emission, although slight blue emission is observed in the fluorescent spectrum for the thin film, indicating that benzothiadiazole part plays a role of an effective trap site. Devices based on polyfluorene homopolymer doped with block copolymer (10 wt %) or an orange emitting model compound at the corresponding content of benzotiadiazole unit are also fabricated. The device with the model compound exhibits orange emission with Commission Internationale de l'Éclairage (CIE) coordinate of (0.58, 0.42), whereas that with block copolymer pale orange with the coordinate of (0.44, 0.38). This fact is probably due to the preferential distribution of block copolymer at the vicinity of anode via hydrophilic interaction of trioxyethylene side chains with poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate). © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45393.     

Chemical (Sr,Co)-doping effect on critical current density for Dy123 melt-solidified bulks

The dilute impurity doping for CuO-chain site was found to largely improve the critical current properties of both Y123 single crystals and Y123 melt-solidified bulks in our previous study. In addition, dilute Sr-doping to Ba site is also effective for enhancement of J_c without serious decrease in T_c as in the case of dilute Zn doping for CuO₂-plane site. In the present study, we have attempted further enhancement of flux pinning force of the Dy123 melt-solidified bulk, which is essentially more promising materials than Y123, by impurity doping for Cu site in the CuO-chain and for Ba site. Although the (Sr,Co)-co-doped Dy123 melt-solidified bulks showed systematically suppressed T_c with their doping levels, high T_c's well exceeding 90 K were maintained. All the Sr-doped or Co-doped Dy123 bulks exhibited higher J_c than the undoped one. More improved J_c properties were achieved by (Sr,Co)-co-doping, suggesting that pinning potential at local regions around doped impurities become deeper by Co-doping, resulting in stronger point-defect-like pinning sites. In addition, more detailed studies on the dilute Sr-doping and the dilute (Sr,Co)-Co-doping were carried out for Y123 single crystals in order to clarify the difference between their doping effects on the J_c properties. The vortex transition field, H^*, to the disordered state in the M–H loops for the Co-doped Y123 single crystal was located at the lower field than that of the Sr-doped one, meaning that the Co ions strongly affect the vortex system compared with the Sr ions.     

Effect of crystallization temperature of palm oil on its crystallization. IV. The influence of tripalmitoylglycerol (PPP) on the crystallization of 1,3-dipalmitoyl-2-oleoyl-glycerol (POP) and 1,2-dioleoyl-3-palmitoyl-glycerol (POO)

Triacylglycerin in Palm Oil contains POP (1,3-dipalmitoyl-2-oleoyl-glycerol) at 30%, POO (1,2-dioleoyl-3-palmitoyl-glycerol) at 20% and PPP (tripalmitoylglycerol) at 5%. The crystallization temperature of PPP is high and the rates of crystal nuclear formation and growth are fast. It is thus considered that PPP may have some effect on the manner or mode of Palm Oil. Examination was thus made to clarify how PPP may affect the crystallization of POP and POO by differential scanning calorimetry (DSC) and X ray diffractometry (XRD) conducted on PPP/POP and PPP/POO mixtures. High and low temperature peaks were noted to appear on the DSC crystallization curve for either of these mixtures. The high temperature peak was considered possibly due to PPP, and the low temperature peak, to POP or POO. DSC isothermal analysis indicated the rate of crystal growth of either mixture to exceed that of pure of POP or POO. Crystal mixture structure was also seen to be complicated than either compound in pure form. The present findings thus clearly indicate that clarification should be made of the effects of high melting point triacylglycerin, such as PPP, on the crystallization of Palm Oil.     

Enzymatic production of fructose 1,6-diphosphate using crude cell extract of Bacillus stearothermophilus

The enzymatic production of fructose 1,6-diphosphate (FDP) from glucose was performed in a batch reactor and a semibatch reactor using the crude cell extract of Bacillus stearothermophilus which contains all four enzymes required for the synthesis. The experimental results of the yield and the time courses of FDP production obtained using various enzyme concentrations were in good agreement with the theoretical predictions calculated based on the differential equations including the rate equations of the four enzymes, which were determined using the purified enzymes of B. stearothermophilus.     

Lipid production by Lipomyces starkeyi using sap squeezed from felled old oil palm trunks

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Growth-induced atomic step ordering on patterned and non-patterned Si(111)

Atomic step configurations on the vicinal surfaces of patterned and non-patterned Si(111) during homoepitaxial step-flow growth were studied as a function of film thickness, deposition temperature, deposition rate, and substrate miscut. We found, for the first time, that step-flow growth on the vicinal surfaces of Si(111) miscut toward the [11 ] direction results in the formation of collective, in-phase zigzag arrays of [2 ]- and [1̄21̄]-type steps. We also found that step-flow growth on the lower-level region around the edge of Si(111) mesa ridges significantly improves period uniformity. We explained the shape of atomic steps on the basis of the stability of surface reconstruction on Si(111), and the atomic step ordering on the assumption of the anisotropic barrier for diffusion at the growing steps.