Transition metal-free Suzuki type cross-coupling reaction for the synthesis of dissymmetric ketones

A simple, efficient and metal-free route for the synthesis of dissymmetric ketones through Suzuki type cross-coupling reaction has been established. This strategy signifies an attractive, cost-effective and operationally convenient tool for the synthesis of a wide range of dissymmetric ketones. Although conventional routes for the synthesis of ketones have been widely used, the potential challenge with these methods is functional group tolerance. The reported metal-free method represents a reaction with moderate functional group tolerance. The procedure is operationally convenient and shows broad substrate scope with good to excellent product yields.     

Magnetic, magnetocaloric, and magnetotransport properties of RCo1.8Mn0.2 (R=Er, Ho, Dy, and Tb) compounds

The magnetic, magnetocaloric, and magnetotransport properties of RCo_1.8Mn_0.2 (R=Er, Ho, Dy, and Tb) were studied by room temperature X-ray diffraction, magnetization, and resistivity measurements at a temperature interval of 5-400 K and magnetic fields up to 5 T. The Curie temperature of RCo₂ was found to increase significantly when 10% Mn was substituted for Co. The effective paramagnetic moments were found to be in reasonable agreement with their theoretical values. A large magnetoresistance (MR) of Δρ/ρ_o≈−13.5% for R=Ho at T≈153 K for ΔH=5 T has been observed. The maximum relative cooling capacities vary from 467 J/kg at low temperature for R=Er to 202 J/kg at the near room temperature for R=Tb.     

Sulfonyl fluorides as privileged warheads in chemical biology

Sulfonyl fluoride electrophiles have found significant utility as reactive probes in chemical biology and molecular pharmacology. As warheads they possess the right balance of biocompatibility (including aqueous stability) and protein reactivity. Their functionality is privileged in this regard as they are known to modify not only reactive serines (resulting in their common use as protease inhibitors), but also context-specific threonine, lysine, tyrosine, cysteine and histidine residues. This review describes the application of sulfonyl fluoride probes across various areas of research and explores new approaches that could further enhance the chemical biology toolkit. We believe that sulfonyl fluoride probes will find greater utility in areas such as covalent enzyme inhibition, target identification and validation, and the mapping of enzyme binding sites, substrates and protein–protein interactions.     

Discovery of novel inhibitors for <Emphasis Type="Italic">Leishmania</Emphasis> nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization

Nucleoside diphosphate kinases (NDKs) are ubiquitous enzymes that catalyze the transfer of the γ-phosphate moiety from an NTP donor to an NDP acceptor, crucial for maintaining the cellular level of nucleoside triphosphates (NTPs). The inability of trypanosomatids to synthesize purines de novo and their dependence on the salvage pathway makes NDK an attractive target to develop drugs for the diseases they cause. Here we report the discovery of novel inhibitors for Leishmania NDK based on the structural and functional characterization of purified recombinant NDK from Leishmania amazonensis. Recombinant LaNDK possesses auto-phosphorylation, phosphotransferase and kinase activities with Histidine 117 playing an essential role. LaNDK crystals were grown by hanging drop vapour diffusion method in a solution containing 18% PEG-MME 500, 100 mM Bis-Tris propane pH 6.0 and 50 mM MgCl₂. It belongs to the hexagonal space group P6₃22 with unit cell parameters a?=?b?=?115.18, c?=?62.18 Å and α?=?β?=?90°, γ?=?120°. The structure solved by molecular replacement methods was refined to crystallographic R-factor and R_free values of 22.54 and 26.52%, respectively. Molecular docking and dynamics simulation-based virtual screening identified putative binding compounds. Protein inhibition studies of selected hits identified five inhibitors effective at micromolar concentrations. One of the compounds showed ~45% inhibition of Leishmania promastigotes proliferation. Analysis of inhibitor-NDK complexes reveals the mode of their binding, facilitating design of new compounds for optimization of activities as drugs against leishmaniasis.     

Non-surface activity and micellization behavior of cationic amphiphilic block copolymer synthesized by reversible addition-fragmentation chain transfer process

Cationic amphiphilic diblock copolymers of poly(n-butylacrylate)-b-poly(3-(methacryloylamino)propyl)trimethylammonium chloride) (PBA-b-PMAPTAC) with various hydrophobic and hydrophilic chain lengths were synthesized by a reversible addition-fragmentation chain transfer (RAFT) process. Their molecular characteristics such as surface activity/nonactivity were investigated by surface tension measurements and foam formation observation. Their micelle formation behavior and micelle structure were investigated by fluorescence probe technique, static and dynamic light scattering (SLS and DLS), etc., as a function of hydrophilic and hydrophobic chain lengths. The block copolymers were found to be non-surface active because the surface tension of the aqueous solutions did not change with increasing polymer concentration. Critical micelle concentration (cmc) of the polymers could be determined by fluorescence and SLS measurements, which means that these polymers form micelles in bulk solution, although they were non-surface active. Above the cmc, the large blue shift of the emission maximum of N-phenyl-1-naphthylamine (NPN) probe and the low micropolarity value of the pyrene probe in polymer solution indicate the core of the micelle is nonpolar in nature. Also, the high value of the relative intensity of the NPN probe and the fluorescence anisotropy of the 1,6-diphenyl-1,3,5-hexatriene (DPH) probe indicated that the core of the micelle is highly viscous in nature. DLS was used to measure the average hydrodynamic radii and size distribution of the copolymer micelles. The copolymer with the longest PBA block had the poorest water solubility and consequently formed micelles with larger size while having a lower cmc. The "non-surface activity" was confirmed for cationic amphiphilic diblock copolymers in addition to anionic ones studied previously, indicating the universality of non-surface activity nature.     

The warm inflationary universe

In the past decade, the importance of dissipation and fluctuation to inflationary dynamics has been realized and has led to a new picture of inflation called warm inflation. Although these phenomena are common to condensed matter systems, for inflation models their importance has only recently started to be appreciated. The article describes the motivation for these phenomena during inflation and then examines their origins from first principles quantum field theory treatments of inflation models. Cosmology today is a data intensive field and this is driving theory to greater precision and predictability. This opens the possibility to consider tests for detecting observational signatures of dissipative processes, which will be discussed. In addition, it will be discussed how particle physics and cosmology are now working in tandem to push the boundaries of our knowledge about fundamental physics.     

Radioisotope sources for X-ray fluorescence analysis

Problems involved in developing radioisotope sources and the characteristics of potentially useful radioisotopes for X-ray fluorescence analysis are presented. Some of the isotopes, which are not in use but look very promising, are indicated.     

A novel study of charged carbon clusters using a tandem Van de Graaff accelerator

A conventional tandem Van de Graaff accelerator is used to produce charged carbon cluster beams. The unique capability of the method for studying highly charged clusters unaccessible to other methods of producing cluster beams is demonstrated.     

Fission track annealing and age determination of hornblende

Hornblende which occurs in igneous and metamorphic rocks is well suited for age determination by the fission track method. The tracks which are readily etched in hydrofluoric acid are annealed in 1 hr at 530° C. Extrapolation of the experimentally determined temperatures suggest that a temperature of 200° C for one m.y. will erase all the tracks present before the heating. Fission track ages of hornblende agree with the main orogenic metamorphic cycles.