Two Methods,One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses

In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein–ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein–ligand complexes.     

Rare-earth free sensitizer in NaLuCrF4:Er upconversion material

Upconversion phosphors are known as a material system that can convert near-infrared light into visible/ultraviolet emissions by sequentially absorbing multiple photons. The studies on upconversion materials often use two rare earth (RE) ions as a sensitizer-activator pair. We investigated the influences on luminescence intensity depending on Cr-doping content (x) of hexagonal NaLu_0.98–xCr_xF₄Er_0.02 (x = 0–0.9) upconversion material by substituting Lu³⁺ ions with Cr³⁺in the absence of Gd³⁺. The change in upconversion luminescence intensity appears with saddle-like shape. We suggest that Cr³⁺ ions play the dual role as a constituent in host lattice and a sensitizer in the upconversion process. Optimal conditions for gaining the strongest upconversion emission correspond to x = 0.3–0.5, where there are effective energy transfers between Cr³⁺ and Er³⁺ ions and CrEr dimers. Apart from these values, the emission intensity decreases rapidly which can be ascribed to the absence of multiple-photon absorption for the case of low Cr³⁺ contents, and to the coupling between Cr³⁺ and/or Er³⁺ ions for the case of high Cr³⁺ contents. Magnetization and electron-spin-resonant measurements were performed to understand the correlation between the optical and magnetic properties.     

Pull-Down of Metalloproteins in Their Native States by Using Desthiobiotin-Based Probes

One-third of all proteins are estimated to require metals for structural stability and/or catalytic activity. Desthiobiotin probes containing metal binding groups can be used to capture metalloproteins with exposed active-site metals under mild conditions so as to prevent changes in metallation state. The proof-of-concept was demonstrated with carbonic anhydrase (CA), an open active site, Zn²⁺-containing protein. CA was targeted by using sulfonamide derivatives. Linkers of various lengths and structures were screened to determine the optimal structure for capture of the native protein. The optimized probes could selectively pull down CA from red blood cell lysate and other protein mixtures. Pull-down of differently metallated CAs was also investigated.     

The Effect of Branched-Chain Fatty Acid Alkyl Esters on the Cold-Flow Properties of Biodiesel

Biodiesel (fatty acid methyl esters [FAME]) is produced from various fats, oils, and greases (FOG) using catalytic transesterification with methanol. These fuels have poor cold-flow properties depending on the fatty acid (FA) composition of the parent FOG. Improving the cold-flow properties of biodiesel will enhance its prospects for use during cooler months in moderate temperature climates. This work is a study on the use of skeletally branched-chain alkyl esters (BCAE) composed of the isopropyl, n-butyl, and 2-ethylhexyl esters of iso-oleic acid isomers (iPr-iOL, nBu-iOL, and 2EH-iOL). These BCAE additives were tested in blends with linear-FAME (L-FAME) derived from soybean oil (SME), lard (LME), tallow (TME), and sewage scum grease (SGME). Binary L-FAME/SME admixtures were also studied. Admixtures were tested for the effects of the additives on cloud point (CP), pour point (PP), and kinematic viscosities at standard (ν⁴⁰ = 40 °C) and low temperatures (T_L) = CP + 5 °C (ν^L). Although the BCAE additives were more effective than SME, relatively large additive concentrations (y_Add) were needed to depress CP and PP by more than 2 °C. Admixtures with high concentrations of BCAE additive had ν⁴⁰ > 6.0 mm² s⁻¹, the maximum limit in ASTM fuel specification D 6751. While the iPr-iOL and nBu-iOL additives may be blended at concentrations up to y_Add = 0.50, 2EH-iOL should not exceed y_Add = 0.28 in LME, 0.31 in SGME, 0.35 in TME, or 0.41 in SME to avoid driving the admixture out of specification. Some anomalies observed in the results at low y_Add for SGME/BCAE admixtures were speculated to have been affected by the low-temperature rheology of SGME.     

Performance comparison of parallel ILU preconditioners for the incompressible Navier-Stokes equations

Journal of Mechanical Science and Technology - In this paper, the performances of various ILU type parallel preconditioners for the finite element discretization of the incompressible Naiver-Stokes...     

Hydrogen production enhancement using hot gas cleaning system combined with prepared Ni-based catalyst in biomass gasification

This paper investigates the hot gas temperature effect on enhancing hydrogen generation and minimizing tar yield using zeolite and prepared Ni-based catalysts in rice straw gasification. Results obtained from this work have shown that increasing hot gas temperature and applying catalysts can enhance energy yield efficiency. When zeolite catalyst and hot gas temperature were adjusted from 250 °C to 400 °C, H₂ and CO increased slightly from 7.31% to 14.57%–8.03% and 17.34%, respectively. The tar removal efficiency varies in the 70%–90% range. When the zeolite was replaced with prepared Ni-based catalysts and hot gas cleaning (HGC) operated at 250 °C, H₂ contents were significantly increased from 6.63% to 12.24% resulting in decreasing the hydrocarbon (tar), and methane content. This implied that NiO could promote the water-gas shift reaction and CH₄ reforming reaction. Under other conditions in which the hot gas temperature was 400 °C, deactivated effects on prepared Ni-based catalyst were observed for inhibiting syngas and tar reduction in the HGC system. The prepared Ni-based catalyst worked at 250 °C demonstrate higher stability, catalyst activity, and less coke decomposition in dry reforming. In summary, the optimum catalytic performance in syngas production and tar elimination was achieved when the catalytic temperature was 250 °C in the presence of prepared Ni-based catalysts, producing 5.92 MJ/kg of lower heating value (LHV) and 73.9% tar removal efficiency.     

Dielectric strength of Al2O3/silicone composites after high‐temperature aging

Silicones are widely used for electrical insulation owing to their high dielectric strength and thermal stability. However, recent studies revealed insufficient stability of silicone for high‐temperature applications. To study the effect of Al₂O₃ fiber on silicone stability, we measured the dielectric strength of unfilled silicone and Al₂O₃/silicone composites as a function of aging time at 250°C in air and analyzed data by Weibull probability distribution to determine characteristic dielectric strength (E₀) and shape parameter (β). Prior to aging, unfilled silicone and composites had similar behavior, with E₀ at about 20 kV/mm and β > 15. During aging, unfilled silicone developed both micro‐ and macrocracks, with β dropped below five in 240 h and E₀ decreased significantly. Composites developed microcracks, with β dropped below 5 in longer time and E₀ remained almost constant. Addition of Al₂O₃ slowed down crack growth in silicone matrix, resulting in longer lasting high‐temperature dielectric materials. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41170.     

Regioselective Synthesis of Naphtho‐fused Heterocycles via Palladium(0)‐Catalyzed Tandem Reaction of N‐Tosylhydrazones

We have developed a palladium(0)‐catalyzed tandem process which involves the cross‐coupling reaction of N‐tosylhydrazones with dibromide compounds followed by a sequence of intramolecular 5‐exo‐trig, 3‐exo‐trig cyclization, ring opening, and β‐hydride elimination to produce 6‐endo‐trig cyclized products. The strategy was successfully applied for the regioselective synthesis of substituted benzo[b]naphtho[2,1‐d]thiophenes, naphtho[1,2‐b]benzofurans, and benzo[a]carbazoles in moderate to excellent yields.

     

Lewis Base Additives Improve the Zeolite Ferrierite‐Catalyzed Synthesis of Isostearic Acids

Isostearic acids (IA) are highly utilized for industrial purposes especially in the area of biolubricants, such as cosmetics and slip additives for polyolefin and related copolymer films. This study was designed to develop a zeolitic catalysis process for efficient IA production through isomerization of fatty acids. The process utilized zeolite protonated Ferrierite with a small amount of base additive to neutralize (i.e., poison) the acidic sites on the external surfaces of the zeolite particles to prevent side reactions. Of the six base additives examined, the proton sponge combined with the zeolite protonated Ferrierite was found to be the most effective for this isomerization. With only 0.5 wt% proton sponge additive to 5.0 wt% Ferrierite, the dimers were successfully suppressed from 20.6 wt% yield to 2.42 wt% with an IA yield of 83.4 wt% and a 98 % conversion.     

A filtration model for prediction of local flux distribution and optimization of submerged hollow fiber membrane module

A filtration mathematical model was developed on the basis of complete mass balance and momentum balance for the local flux distribution prediction and optimization of submerged hollow fiber membrane module. In this model, the effect of radial permeate flow on internal flow resistance was considered through a slip parameter obtained from the local flux experiments. The effects of fiber length, inside diameter, and average operating flux on local flux distribution were investigated using this model. The predicted results were in good agreement with the experimental data obtained from literature. It was also found that the asymmetry distribution of local flux could be intensified with the increase of average operating flux and fiber length, but slowed down with the increase of fiber inside diameter. Furthermore, the simulation coupled with energy consumption analysis could efficiently predict and illustrate the relationship between fiber geometry and water production efficiency. © 2015 American Institute of Chemical Engineers AIChE J, 61: 4377–4386, 2015