Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology

For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.     

Hollow N-ZIFs@NiCo-LDH as highly efficient catalysts for 4-nitrophenol and dyes

N-ZIF-(1:0)@NiCo-LDH, N-ZIF-(1:3.5)@NiCo-LDH and N-ZIF-(0:1)@NiCo-LDH were prepared by mixing solvents in various volume ratios (V_methanol:V_water = 1:0, 1:3.5 and 0:1) when synthesizing precursors. These composite materials were characterized using scanning and transmission electron microscopies, X-ray diffraction, X-ray photoelectron spectroscopy and nitrogen adsorption–desorption measurements, and investigated as catalysts for reduction of 4-nitrophenol, methyl orange and methylene blue. The NaBH₄ concentration as an important factor that may affect catalytic activity for reduction of 4-nitrophenol was examined. Under optimal experimental conditions, the excellent catalytic activity of the N-ZIF-(0:1)@NiCo-LDH composite, compared to that of N-ZIF-(1:0)@NiCo-LDH and N-ZIF-(1:3.5)@NiCo-LDH composites, could be attributed to the presence of graphitic nitrogen. In addition, compared with previously reported catalysts, all catalysts prepared show excellent catalytic activity owing to the unique structure exposing more active sites.     

A facile way to rejuvenate Ag3PO4 as a recyclable highly efficient photocatalyst

Recycling awarded the silver: Ag(3)PO(4), a highly efficient photocatalyst, decomposes to the weak photocatalyst Ag during consecutive photocatalytic cycles. A facile and very mild wet chemical oxidation method was proposed, which involves the cooperation of H(2)O(2) with Na(2)HPO(4), to rejuvenate Ag(3)PO(4) from Ag as a recyclable highly efficient photocatalyst.     

4-磺酰胺-L-脯氨酸衍生物的合成及其水相中不对称催化Aldol反应的性能（英文）

以4-羟基-L-脯氨酸为原料合成了4-对甲基苯磺酰胺-L-脯氨酸催化剂1a-b,通过IR,1~H NMR和HR MS对其结构进行了表征,并考察了其水相中对不对称Aldol反应的催化性能.结果表明两种催化剂在水相中均能很好的催化Aldol反应,仅用5mol%的催化剂即可得到很好的催化效果,产率高达93%,非对映选择性高达94∶6,而对映选择性高达99%.     

Electrochemical radical reactions of alkyl iodides: a highly efficient,clean, green alternative to tin reagents

An electrochemical ‘redox-relay’ system has been developed which allows the generation of C-centered radicals. Intermolecular ‘tin-like’ radical reactions can subsequently be conducted under the most benign of conditions. The yields and efficiency of the processes are competitive and even superior in most cases to comparable conditions with tributyltin hydride. The use of air and electricity as the promotor (instead of a tin or other reagent) combined with the aqueous reaction media make this a clean and ‘green’ alternative to these classic C–C bond forming processes.

A ‘green’ and high-yielding electrochemical method for performing tin-free, intermolecular radical reactions (the Giese reaction) has been developed.     

Application of potassium-modified carbon nitride as a highly efficient recyclable catalyst for synthesis of 4H-chromene derivatives

A potassium-doped carbon nitride (K-CN) was prepared by a simple thermal polymerization method. The prepared K-CN was characterized by Fourier infrared spectroscopy (FT-IR), powder X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS) techniques. The obtained K-CN exhibited excellent catalytic activity for synthesis of 4H-chromene derivatives via one-pot three-component reaction of salicylaldehyde, cyclohexane-1,3-diones and 4-hydroxycoumarin in water/ethyl lactate at room temperature. The reported method shows significant advantages, such as high yield, mild and clean reaction conditions, the use of recyclable catalyst and ethyl lactate/water as an environmentally friendly solvent, multi-component reaction at room temperature, no chromatographic separation and suitable for large-scale synthesis.

     

Sequential testing as an efficient screening method for interferences in routine analysis as applied to atomic-absorption spectrometry with flame and graphite furnace atomization

Reliable standardization is a serious problem for most analytical methods. In spite of extensive work on interferences, the results are not suited for prediction of gross errors in any particular case. This paper is intended to show the power of sequential testing in practical atomic-absorption spectrometric analyses for the efficient detection of interferences causing changes in sensitivity; this test is carried out by comparing the sensitivity of the standard with the sensitivity for the sample, as determined by the difference between the signals for the spiked and unspiked samples. The simple computations can be carried out instantly and experimentation is terminated as soon as a conclusion can be drawn. The major advantage over the traditional tests lies in the smaller number of independent measurements, requiring less time and sample. Three separate cases are discussed: with the mean sensitivity of the standard known and the deviation expected to occur in one direction only (single-sided alternative hypothesis); with the standard deviation of the determination known and the deviation possibly occurring in both directions (double-sided alternative hypothesis); and with the mean and the standard deviation unknown but estimated during the test (sequential t-test). It is shown that assumptions about the normal distribution of the data do not impose serious restrictions in practical AAS work.     

4-Trifluoromethanesulfonamidyl prolinol tert-butyldiphenylsilyl ether as a highly efficient bifunctional organocatalyst for Michael addition of ketones and aldehydes to nitroolefins

4-Trifluoromethanesulfonamidyl prolinol tert-butyldiphenylsilyl ether bifunctional organocatalyst 3a is a highly efficient catalyst for the asymmetric Michael addition reactions of ketones and aldehydes to nitrostyrenes, leading to syn-selective adducts with excellent yields (>99%), high diastereoselectivities (up to 99:1 dr) and excellent enantioselectivities (up to 99% ee). Control experiments suggested that the trans-configuration relationship between the bulky group (-CH₂OTBDPS) and the sulfonamido group at the 4-position of the pyrrolidine ring was important to achieve high yield and stereoselectivity.     

Genesis of thiacalixarenes: a one-pot highly efficient synthesis of TC4A

This Letter reports the results of our studies towards the synthesis of thiacalixarenes. In an effort to develop an efficient and inexpensive synthetic methodology for thiacalixarenes, several trials were conducted to study the effect of base/template, solvents, catalyst, phenol substitutions and temperature profile. Microwave synthesis was also tested to reduce the overall time for the reaction. Based on the results of these investigations, a detailed reaction mechanism is proposed and an optimized synthetic procedure for p-tert-butylthiacalix[4]arene is demonstrated.     

HClO4-SiO2 as a new, highly efficient, inexpensive and reusable catalyst for N-tert-butoxycarbonylation of amines

Perchloric acid adsorbed on silica-gel (HClO4-SiO2) was found to be a new, highly efficient, inexpensive and reusable catalyst for chemoselective N-tert-butoxycarbonylation of amines at room temperature and under solvent-free conditions.     

N-Sulfonic acid poly(4-vinylpyridinium) chloride as a highly effcient and reusable catalyst for the Biginelli reaction简

A mild, simple and efficient procedure for the preparation of 3,4-dihydropyrimidin-2（1H）-ones and -thiones is described using N-sulfonic acid poly（4-vinylpyridinium） chloride （NSPVPC） as a heterogeneous and efficient catalyst under solvent-free conditions. Simple methodologies, easy work-up procedure, easy preparation of the catalyst, excellent yields and very short reaction times are among the other advantages of this work. Further, the catalyst can be reused and recovered for several times without significant decrease in its activity.     

Rattle-type microspheres as a support of tiny gold nanoparticles for highly efficient catalysis

SiO(2)/poly(ethyleneglycol dimethacrylate) (PEGDMA) rattle-type microspheres loaded with tiny sized gold nanoparticles (~2 nm) were prepared through a facile and novel method. Catalyzed reduction of 4-nitrophenol with NaBH(4) demonstrated that this rattle-type microsphere possessed high catalytic efficiency.     

C2-symmetric bisprolinamide as a highly efficient catalyst for direct aldol reaction

[reaction: see text] The catalytic activity of the prolinamide-type catalysts may be improved by introducing additional prolinamide moiety into the catalyst, while the enantioselectivity can still be maintained or further improved. A C2-symmetric bisprolinamide with two prolinamide moieties has been found to be an excellent catalyst for direct aldol reaction with more than doubled reactivity and better asymmetric induction than its monoprolinamide counterpart.     

The Co_3O_4 nanosheet array as support for MoS_2 as highly efficient electrocatalysts for hydrogen evolution reaction

The electrochemical hydrogen evolution reaction(HER) on a non-precious electrocatalyst in an alkaline environment is of essential importance for future renewable energy. The design of advanced electrocatalysts for HER is the most important part to reduce the cost and to enhance the efficiency of water splitting. MoS_2 is considered as one of the most promising electrocatalysts to replace the precious Pt catalyst.Herein, for the first time, we have successfully loaded MoS_2 electrocatalysts onto the Co_3O_4 nanosheet array to catalyze HER with a low onset potential of ~76 mV. The high hydrogen evolution activity of MoS_2 supported on the Co_3O_4 nanosheet array may be attributed to the increased active sites and the electronic interactions between MoS_2 and Co_3O_4.     

Zirconium nitride as a highly efficient nitrogen source to synthesize the metal nitride clusterfullerenes

Metal nitride clusterfullerenes(NCFs)have significant applications in molecular electronics,biomedical imaging,and nonlinear optical devices due to their unique structures.However,their wide applications are limited by the production quantity.In this work,the yields of metal nitride clusterfullerenes M3N@C80(M=Y,Sc,Gd)were greatly enhanced by utilizing zirconium nitride(Zr N)as an efficient nitrogen source for the arc-discharge method.Compared with the traditional synthetic route using N2gas as nitrogen source,the Zr N inside graphite tube can be vaporized simultaneously with metal and graphite,and then afford the high concentration of nitrogen atoms in the arc region,which will promote the formation of metal nitride clusterfullerenes finally.The Zr N can promote the yields of Y3N@C80,Sc3N@C80and Gd3N@C80,revealing the universal applicability of Zr N as a highly efficient nitrogen source.Specifically,the yield of Sc3N@C80was greatly improved when adding Zr N,and it shows over double yield compared to traditional synthetic route using N2gas.In addition,Zr N can also enhance the yields of paramagnetic azametallofullerene M2@C79N due to the high concentration of nitrogen atoms in the arc region.This new method enhances the production quantity of metal nitride clusterfullerenes and azametallofullerenes,and it will greatly promote the research and application of these molecular carbon materials.     

KHSO4: a highly efficient and reusable heterogeneous catalyst for hydroarylation of styrenes

Abstract  

Hydroarylation of styrenes with arenes/heteroarenes using KHSO₄ (10 mol%) as an efficient heterogeneous catalyst is described. High conversion and selectivity (>99%) were observed for hydroarylation of styrenes with 2-naphthol at reflux temperature of 1,2-dichloroethane. Yields were quantitative with all styrenes. Moderate to good conversions and selectivities were achieved with other aromatics and heteroaromatics under the same conditions. Regeneration and reusability of KHSO₄ were demonstrated. Addition of a trace amount of water could help to reactivate the KHSO₄ through dispersion and to facilitate the hydroarylation reaction.     

New β-amino thiols as efficient catalysts for highly enantioselective alkenylzinc addition to aldehydes

A series of new optically active β-amino thiols and thiolacetates prepared from the simple natural amino acid, (S)-(−)-valine, were found to be effective catalysts for the enantioselective addition of alkenylzinc to aldehydes and thereby providing an efficient route for chiral (E)-allylic alcohols with ees of up to >99% in the presence of 7a (1 mol %).     

Cu@KCC-1-NH-CS2 as a new and highly efficient nanocatalyst for the synthesis of 2-amino-4H-chromene derivatives

In the present work, Cu@KCC-1-NH-CS₂ as a green, efficient, and reusable nano-reactor was designed and used for the one-pot, three-component synthesis of 2-amino-4H-chromene derivatives using the reaction of cyclic 1,3-diketones, arylglyoxals, and malononitrile, under reflux conditions in EtOH. Engineered nanocatalyst characterized using different methods including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), adsorption/desorption analysis (BET), and energy dispersive X-ray spectroscopy (EDS). According to the obtained results, presented protocol for the synthesis of 2-amino-4H-chromenes using Cu@KCC-1-NH-CS₂ gave the desired products in higher yields (89–98%) with short reaction times. Also, under mild reaction conditions this green nanocatalyst indicated recyclable behavior five times with minor reduce in its catalytic activity.