Search

A method is developed for assembling the azaanthraquinone skeleton from N-propargylamino quinone by a Au(I)-catalyzed 6-endo-dig cycloisomerization. The catalytic process is applied for preparing alkaloid cleistopholine and its analogues.

An investigation is carried out about [H.sub.2]S adsorption and dissociation on the gallium-rich GaAs(001)-4 x 2 surface by using hybrid density functional theory. The calculation results show that transfer of one H atom from the chemisorbed [H.sub.2]S to a second-layer As atom, with an activation barrier of 8.2 kcal/mol, is more kinetically favorable than insertion of an H atom into the Ga dimer bond or transfer of one H atom to the other Ga dangling bonds.

In situ scanning tunneling microscopy (STM) and cyclic voltammetry are employed to investigate the adsorption of organic molecules with different functional groups on Cu(111) in a 0.1 M HCIO4 solution. The molecules of cyanuric acid, cyanuric chloride, and 1,3,5-tribromo-benzene adsorb on the Cu(111) electrode surface and form well-defined adlayers with (3 x 3) structure in the double layer potential region.

Direct evidence on the adsorption mode of cinchonidine on Cu(100) surface was found by using scanning tunneling microscopy (STM). The internal structure and coordination of the molecules with Cu(100) surface were very clearly revealed in a high resolution STM image.

We have identified two chemotypes of CREBBP bromodomain ligands by fragment-based high-throughput docking. Only 17 molecules from the original library of two-million compounds were tested in vitro. Optimization of the two low-micromolar hits, the 4-acylpyrrole 1 and acylbenzene 9, was driven by molecular dynamics results which suggested improvement of the polar interactions with the Arg1173 side chain at the rim of the binding site. The synthesis of only two derivatives of 1 yielded the 4-acylpyrrole 6 which shows a single-digit micromolar affinity for the CREBBP bromodomain and a ligand efficiency of 0.34 kcal/mol per non-hydrogen atom. Optimization of the acylbenzene hit 9 resulted in a series of derivatives with nanomolar potencies, good ligand efficiency and selectivity (see Unzue , A. ; Xu , M. ; Dong , J. ; Wiedmer , L. ; Spiliotopoulos , D. ; Caflisch , A. ; Nevado , C. Fragment-Based Design of Selective Nanomolar Ligands of the CREBBP Bromodomain . J. Med. Chem. 2015 , DOI: 10.1021/acs.jmedchem.5b00172 ). The in silico predicted binding mode of the acylbenzene derivative 10 was validated by solving the structure of the complex with the CREBBP bromodomain. [ABSTRACT FROM AUTHOR]

Novel ligands of the CREBBP bromodomain were identified by fragment-based docking. The in silico discovered hits have been optimized by chemical synthesis into selective nanomolar compounds, thereby preserving the ligand efficiency. The selectivity for the CREBBP bromodomain over other human bromodomain subfamilies has achieved by a benzoate moiety which was predicted by docking to be involved in favorable electrostatic interactions with the Arg1173 side chain, a prediction that could be verified a posteriori by the high-resolution crystal structure of the CREBBP bromodomain in complex with ligand 6 and also by MD simulations (see Xu , M. ; Unzue , A. ; Dong , J. ; Spiliotopoulos , D. ; Nevado , C. ; Caflisch , A. Discovery of CREBBP bromodomain inhibitors by high-throughput docking and hit optimization guided by molecular dynamics. [ABSTRACT FROM AUTHOR]

Cefuroxime axetil (CFA) drug nanoparticles were prepared by liquid antisolvent precipitation in a microchannel system with a T-shaped junction formed by a main microchannel and a branch. Isopropyl ether as the antisolvent (high flow rate) was usually passed through the main microchannel, and CFA acetone solution as the solvent (low flow rate) was injected into the branch simultaneously. The solvent diffused from the CFA acetone solution stream into the antisolvent phase, which resulted in the supersaturation of CFA and thus led to the rapid precipitation of CFA nanoparticles. The change of the injection phase from CFA acetone solution to isopropyl ether was found to have a significant effect on the formation of CFA nanoparticles owing to the different contact behavior. The morphology and size of CFA nanoparticles were characterized by scanning electronic microscopy (SEM) and particle size distribution (PSD) measurements by laser diffractometry. Furthermore, the effects of CFA acetone solution velocity, antisolvent velocity, overall velocity, and CFA concentration on the particle size and size distribution were experimentally investigated. The as-prepared CFA nanoparticles were amorphous and exhibited a higher dissolution rate than raw CFA. This work suggests that microfluidics might find wide applications in the development and optimization of drug nanoparticles in the newly emerging field of nanomedicine. [ABSTRACT FROM AUTHOR]

Riser hydrodynamics in a circulating fluidized bed are investigated experimentally and numerically by changing the composition of the fluidizing gas. Helium gas is added to air in the range of 0 to 96 vol % for fluidizing FCC particles 78 μm in size and density of 1560 kg/m3. Increasing He concentration decreases the fluidizing gas density and viscosity. The effect of change in gas composition is measured through the change in voidage along the riser from the pressure drop and the solids circulation rate, while analyzed by changes in slip velocity and particle Reynolds number. Numerical simulations using Computational Fluid Dynamics (CFD) have successfully predicted the experimental measurements over the entire range of fluidizing gas densities investigated. Simulations have also revealed that interphase momentum exchange in the bottom, accelerated region of the riser is dominated by cluster formation, while individual particle drag was dominant in the upper, more dilute regions. Given that CFD simulations have successfully reproduced these results, a scaling scheme is investigated whereby a hot model unit is simulated keeping either the Archimedes number or the density ratio of particle to gas constant. The results indicated better agreement between experimental and numerical voidage profiles for the density ratio scaling. Using the full set of scaling laws produced excellent prediction of the upper, fully developed region of the riser, but failed in the bottom regions. The scaling error in the bottom region was attributed to the momentum interaction in this region being dominated by cluster formation and not by the drag force on individual particles for which the scaling laws were derived. CFD has shown to be an effective tool in evaluation of scaling laws in risers. [ABSTRACT FROM AUTHOR]

As part of our systematic program on the thermodynamic study of an aqueous solution of glycol ethers, this work reports new measurements of densities and viscosities for the binary liquid mixture of triethylene glycol monoethyl ether (CH3CH2(OCH2CH2)3OH) water as a function of composition in the temperature range from (293.15 to 333.15) K at atmospheric pressure. Densities were determined using a capillary pycnometer. Viscosities were measured with an Ubbelohde capillary viscometer. From the experimental data, the excess molar volumes, VE, and viscosity deviations, δη, were calculated. These data have been correlated by the Redlich−Kister type equations to obtain their coefficients and standard deviations. The results suggest that the molecular interaction between triethylene glycol monoethyl ether and water is stronger than that of diethylene glycol monoethyl ether and water. [ABSTRACT FROM AUTHOR]

Using the HIV-1 protease binding mode of MK-8718 and PL-100 as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral activity relative to MK-8718 ., Competing Interests: The authors declare no competing financial interest.

A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.