Enantio- and Regioselective Copper-Catalyzed 1,2-Dearomatization of Pyridines

A copper-catalyzed dearomative alkynylation of pyridines is reported with excellent regio- and enantioselectivities. The synthetically valuable enantioenriched 2-alkynyl-1,2-dihydropyridine products afforded are generated from the readily available feedstock, pyridine, and commercially available terminal alkynes. The three-component reaction between a pyridine, a terminal alkyne, and methyl chloroformate employs copper chloride and StackPhos, a chiral biaryl P,N- ligand, as the catalytic system. Under mild reaction conditions, the desired 1,2-addition products are delivered in up to 99 % yield with regioselectivity ratios up to 25 : 1 and enantioselectivities values of up to 99 % ee. Activated and non-activated terminal alkynes containing a wide range of functional groups are well tolerated. Even acetylene gas delivered mono-alkynylated products in high yield and ee. Application of the methodology in an efficient enantioselective synthesis of the chiral piperidine indolizidine, coniceine, is reported.     

Laser-Assisted Scalable Pore Fabrication in Graphene Membranes for Blue-Energy Generation

The osmotic energy from a salinity gradient (i. e. blue energy) is identified as a promising non-intermittent renewable energy source for a sustainable technology. However, this membrane-based technology is facing major limitations for large-scale viability, primarily due to the poor membrane performance. An atomically thin 2D nanoporous material with high surface charge density resolves the bottleneck and leads to a new class of membrane material the salinity gradient energy. Although 2D nanoporous membranes show extremely high performance in terms of energy generation through the single pore, the fabrication and technical challenges such as ion concentration polarization make the nanoporous membrane a non-viable solution. On the other hand, the mesoporous and micro porous structures in the 2D membrane result in improved energy generation with very low fabrication complexity. In the present work, we report femtosecond (fs) laser-assisted scalable fabrication of μm to mm size pores on Graphene membrane for blue energy generation for the first time. A remarkable osmotic power in the order of μW has been achieved using mm size pores, which is about six orders of magnitudes higher compared to nanoporous membranes, which is mainly due to the diffusion-osmosis driven large ionic flux. Our work paves the way towards fs laser-assisted scalable pore creation in the 2D membrane for large-scale osmotic power generation.     

A Minimal Functional Complex of Cytochrome P450 and FBD of Cytochrome P450 Reductase in Nanodiscs

Structural interactions that enable electron transfer to cytochrome‐P450 (CYP450) from its redox partner CYP450‐reductase (CPR) are a vital prerequisite for its catalytic mechanism. The first structural model for the membrane‐bound functional complex to reveal interactions between the full‐length CYP450 and a minimal domain of CPR is now reported. The results suggest that anchorage of the proteins in a lipid bilayer is a minimal requirement for CYP450 catalytic function. Akin to cytochrome‐b₅ (cyt‐b₅), Arg 125 on the C‐helix of CYP450s is found to be important for effective electron transfer, thus supporting the competitive behavior of redox partners for CYP450s. A general approach is presented to study protein–protein interactions combining the use of nanodiscs with NMR spectroscopy and SAXS. Linking structural details to the mechanism will help unravel the xenobiotic metabolism of diverse microsomal CYP450s in their native environment and facilitate the design of new drug entities.     

Composite of discotic liquid crystal and gold nanoparticles: A comperative band gap study

Nanocomposites of discotic liquid crystal namely 2, 3, 6, 7, 10, 11-hexabutyloxytryphenylene (HAT4) in existence of variable concentration of gold nanoparticles (GNPs) have been studied at room temperature and zero pressure. The absorption spectra of nanocomposites are captured by a Shimadzu UV–VIS Spectrophotometer, model UV-1800, in the wavelength range 900–200?nm. In this paper using the Tauc’s relation, the absorption spectra fitting method was applied to estimate the optical band gap. Nanocomposites are prepared by mixing of GNPs with four concentrations in pure HAT4 viz. 0.2, 0.6, 1.2 and 3?wt%. From the investigation of absorption spectra, it has been observed that with the enhance of GNPs concentration in pure HAT4 band gap has decreased for lower concentrations but for higher concentration (3?wt%) it increases.     

Synthesis of new bridgehead heterocycles: Pyrimido[3′,2′:3,4]‐1,2,4‐triazino[5,6‐b]indoles

A new bridgehead nitrogen hetero‐ cycle viz. 11‐carboethoxy‐9‐oxo‐pyrimido[3′2′:3,4]‐1,2,4‐triazino[5,6‐b]indole 3 has been synthesized from 3‐azido‐5H‐1,2,4‐triazino[5,6‐b]indole 2 by its reaction with diethyl fumerate. The intermediate 2 was obtained by treating 3‐hydrazino‐5H‐1,2,4‐triazino[5,6‐b]indole with NaNO₂ in presence of polyphosphoric acid. A plausible mechanism for the formation of 3 has been formulated and discussed. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:272–276, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20199     

In vivo metabolic investigation of cetilistat in normal versus pseudo-germ-free rats using UPLC-QTOFMS/MS and in silico toxicological evaluation of its metabolites

Cetilistat (CET) is a pancreatic lipase inhibitor approved for management of obesity after the serious adverse effects exhibited by its analogue orlistat. Exhaustive literature review reveals lack of comprehensive reports on its biotransformation. With a view to study the same, the present study reports the identification and characterization of metabolites of CET in rats using UPLC–MS/MS. As the small intestine is the site of action for CET, it is important that the role of microbial flora in the metabolism of CET be explored. To achieve this, the metabolic profile of CET was compared between normal and pseudo-germ-free rats. The study involved the administration of a drug suspension to male Sprague–Dawley pseudo-germ-free and normal untreated rats followed by collection of urine, feces, and blood at specific intervals. Sample preparation was performed using liquid–liquid extraction and concentration of samples followed by analysis using LC–MS/MS. Finally, an in silico study was performed on the drug and metabolites to predict their toxicological properties using ADMET Predictor^TM software. Four metabolites of CET were observed in in vivo matrices. As expected, significant changes were observed both qualitatively and quantitatively, implying that formation of metabolites was both CYP enzymes and gut microflora mediated.     

Study of quality control and metal distribution in urban airborne particulates

In this investigation, results of 33 elements in airborne samples collected continuously over nine urban locations are discussed. Inductively coupled plasma-atomic emission spectrometry technique was used for determining concentration of metals. Quality control was established prior to analysis of real air samples. The guidelines followed are based on USEPA Compendium Method IO-3.4. Uncertainty in analysis was also established. Based on the concentration of metals in airborne particulates, we attempted to study the metal distribution characteristics in ambient air at various urban locations. Metals such as Al, Ca, Fe were comparatively at higher concentrations than the other elements under study at most of the locations. The city vehicles operate on lead-free fuels; however, concentration of lead in urban dust was observed in the concentration range of 0.33–6.24 μg/m³. Soil samples were also collected from sites close to the air sampling locations. Soil samples were also analysed for metal content. Enrichment factor was determined for elements measured at nine urban locations. The data supports interpretation of results in terms of contribution of metals in airborne particulates from anthropogenic and noncrustal origin.     

l-Asparaginase as Potent Anti-leukemic Agent and Its Significance of Having Reduced Glutaminase Side Activity for Better treatment of Acute Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) is one of the leading types of malignant disorder seen in children. Viral infections, genetic factors and exposure to chemical carcinogens are some of the factors responsible for causing ALL. Treatment strategies followed for curing ALL include chemotherapy or radiation therapy, wherein, chemotherapy involves the use of the enzymatic drug l-Asparaginase. The enzyme can be produced from various plants, animals, bacterial and fungal sources but, among them, bacterial sources are widely used for production of this enzyme. The enzyme is non-human in origin having certain bottle necks with l-Asparaginase therapy in the form of side effects such as pancreatitis, thrombosis which are mainly due to glutaminase side activity. Hence, present-day research is mainly focussed on minimizing or completely eliminating the glutaminase activity of the enzyme l-Asparaginase. This review is focussed on the complications associated with glutaminase side activity and use of glutaminase free enzymatic drug l-Asparaginase in treating ALL and the other developments related to the modification of the drug for quality treatment.