Stereoselective first total synthesis of (R)-rugulactone

A simple and highly efficient stereoselective synthetic route has been developed for the synthesis of (R)-rugulactone, a 6-arylalkyl-5,6-dihydro-2H-pyran-2-one, from readily available substrates such as 1,3-propanediol and 3-phenyl-1-propanal employing Keck’s asymmetric allylation and cross metathesis as key steps.     

Large heat capacity anomaly near the consolute point of the binary mixture nitromethane and 3-pentanol

The large critical anomaly in the isobaric heat capacity C(p,x)(T) of the binary mixture nitromethane + 3-pentanol is measured using high-resolution adiabatic scanning calorimetry. The unique features of this technique provided an alternative approach to the study of the critical behavior of C(p,x)(T), providing further C(p,x)(T) related quantities from which valuable information could be extracted. Our data are in full agreement with the predictions of the Modern Theory of Critical Phenomena; specifically, 3D-Ising model values for the critical exponent α and the universal amplitude ratio values of the leading critical amplitudes, as well as for the first correction-to-scaling ones, provide the optimum fits to represent the experimental data. Evidence for the need of higher-order terms, i.e., first correction-to-scaling term, is given. The large value of the coefficient E for the linear temperature dependence of the background obtained is ascribed to a possible contribution of the regular linear background term, of a higher-order asymmetry term, and of the second correction-to-scaling term. Internal consistency of C(p,x)(T) and its related quantities is successfully checked.     

Quantifying Density Fluctuations in Volumes of All Shapes and Sizes Using Indirect Umbrella Sampling

Water density fluctuations are an important statistical mechanical observable and are related to many-body correlations, as well as hydrophobic hydration and interactions. Local water density fluctuations at a solid-water surface have also been proposed as a measure of its hydrophobicity. These fluctuations can be quantified by calculating the probability, P _v (N), of observing N waters in a probe volume of interest v. When v is large, calculating P _v (N) using molecular dynamics simulations is challenging, as the probability of observing very few waters is exponentially small, and the standard procedure for overcoming this problem (umbrella sampling in N) leads to undesirable impulsive forces. Patel et al. (J. Phys. Chem. B 114:1632, 2010) have recently developed an indirect umbrella sampling (INDUS) method, that samples a coarse-grained particle number to obtain P _v (N) in cuboidal volumes. Here, we present and demonstrate an extension of that approach to volumes of other basic shapes, like spheres and cylinders, as well as to collections of such volumes. We further describe the implementation of INDUS in the NPT ensemble and calculate P _v (N) distributions over a broad range of pressures. Our method may be of particular interest in characterizing the hydrophobicity of interfaces of proteins, nanotubes and related systems.     

Effect of film thickness on the transport properties of MgB2 synthesized by spray pyrolysis

Polycrystalline MgB₂ films of different thickness have been prepared by employing spray pyrolysis technique on MgO (1 0 0) substrate. The MgB₂ and other phases have been confirmed using X-ray diffraction technique and no trace of impurities phases have been found. The resistivity behavior shows that the superconducting transition temperature lies in the range of 37–39 K with narrow transition width. The transport critical current density vary with films thickness and achieved highest value ～1.2 × 10⁶ A/cm² at 20 K for 2.0 μm thick film and its values increase as thickness increases.     

PPAR gamma targeted molecular docking and synthesis of some new amide and urea substituted 1, 3, 4-thiadiazole derivative as antidiabetic compound

The PPAR-γ agonist enhances the insulin sensitivity and avoids the disorganized hyperglycemic by promoting the insulin guided cellular uptake of blood glucose. Therefore, in the present work PPAR-γ has chosen as the target for the molecular docking study to design an effective agonist of the same. By this research work an effort has been made to prepare amide and urea series of 1, 3, 4-thiadiazole derivatives as 4-substituted-N-(5-(4-(1-piperidino)1-piperidinyl)-1,3,4-(2-thiadiazolyl)benzamide (4a-f) and 1-(4-substitutedphenyl)-3-(5-(4-(1-piperidino)1-piperidinyl)-1,3,4-(2-thiadiazolyl)urea (6a-f) . Both the docking score as well as the pharmacological animal study data has been suggested that the electron donating group containing compound 4f and 6f are most potent molecules for the antidiabetic activity close to the standard drug pioglitazone. It was further observed that the unsubstituted aromatic ring containing derivatives have also considerable effect (4a and 6a) than the electron withdrawing containing derivatives. After the comparison of biological data for amide and urea series, it was concluded that the urea (6a-f) series is more effective than the amide series.     

Influence of Amine‐Based Cationic Gemini Surfactants on Catalytic Activity of α‐Chymotrypsin

The α‐chymotrypsin activity was tested in aqueous media with the presence of novel cationic amine–based gemini surfactant, with different spacer chain lengths and head group size, and also compared with the cationic cetyltrimethylammonium bromide (CTAB) and cetyltriphenylphosphonium bromide (CTPB) surfactants and aqueous buffer only. The p‐nitrophenyl acetate (PNPA) hydrolysis rate was monitored in the presence of the surfactant concentration at 30°C. Most of these gemini surfactants gave higher catalytic activity as compared to cationic CTAB and CTPB. The highest superactivity was measured in the presence of gemini 16‐12‐16, [dodecanediyl‐1,12‐bis(cetyldimethylammonium bromide)] surfactant at pH 7.5. The catalytic reaction follows the Michaelis–Menten mechanism. The catalytic rate constants, k_cat, show the same profile that the catalytic affinity; K_M being enhanced with increasing space chain length. The results are favorable for considering that the amine‐based gemini surfactant influences more than both the aqueous and cationic micellar media.     

Can in vitro assays substitute for in vivo studies in assessing the pulmonary hazards of fine and nanoscale materials?

Risk evaluations for nanomaterials require the generation of hazard data as well as exposure assessments. Most of the validated nanotoxicity studies have been conducted using in vivo experimental designs. It would be highly desirable to develop in vitro pulmonary hazard tests to assess the toxicity of fine and nanoscale particle-types. However, in vitro evaluations for pulmonary hazards are known to have limited predictive value for identifying in vivo lung toxicity effects. Accordingly, this study investigated the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoparticle-types following exposures in rats. Initially, complete physicochemical characterization of particulates was conducted, both in the dry and wet states. Second, rats were exposed by intratracheal instillation to 1 or 5 mg/kg of the following particle-types: carbonyl iron, crystalline silica, amorphous silica, nanoscale zinc oxide, or fine zinc oxide. Inflammation and cytotoxicity endpoints were measured at 24 h, 1 week, 1 month and 3 months post-instillation exposure. In addition, histopathological analyses of lung tissues were conducted at 3 months post-exposure. Pulmonary cell in vitro studies consisted of three different culture conditions at 4 different time periods. These included (1) rat L2 lung epithelial cells, (2) primary rat alveolar macrophages, and (3) alveolar macrophage—L2 lung epithelial cell co-cultures which were incubated with the same particles as tested in the in vivo study for 1, 4, 24, or 48 h. Cell culture fluids were evaluated for cytotoxicity endpoints and inflammatory cytokines at the different time periods in an attempt to match the biomarkers assessed in the in vivo study. Results of in vivo pulmonary toxicity studies demonstrated that instilled carbonyl iron particles produced little toxicity. Crystalline silica and amorphous silica particle exposures produced substantial inflammatory and cytotoxic effects initially, but only the crystalline silica variety produced sustained and progressive inflammatory and cytotoxic responses, leading to the development of pulmonary fibrosis. Exposures to nanoscale or fine-sized zinc oxide particles produced potent but typical “metal fume fever”-like reversible inflammation/cytotoxic effects which were resolved by 1-month postinstillation exposure. In contrast to the in vivo results, using cytotoxicity and inflammation endpoints, in vitro effects to the various particle-types were difficult to gauge, owing to the number of variables that were studied (i.e., cell-types, time-course, dose response (including particle overload doses)), and various endpoints (e.g., cytotoxicity = LDH, MTT; inflammation/cytokines = MIP-2). For instance, none of the in vitro endpoints could mimic a transient inflammatory/cytotoxic response—as was measured following exposures to amorphous silica, or fine or nanoscale zinc oxide particles. We conclude that current in vitro cell culture systems do not accurately forecast the pulmonary hazard responses of instilled particle-types. It seems clear that in vitro cellular systems will need to be further developed, standardized, and validated (relative to in vivo effects) in order to provide useful screening data on the relative toxicity of inhaled particles.