Synthesis and EPR studies of vanadyl tetrakis(selenodiazole)porphyrazine

Tetrakis(selenodiazole)porphyrazine and its vanadyl (VO²⁺) complex have been prepared and characterized by FT-IR, UV–vis, and MALDI-MS. The magnetic properties of the complex have been investigated by EPR spectroscopy.     

Uncertainty and value of information when allocating resources within and between healthcare programmes

A two-stage stochastic mathematical programming formulation has been developed to optimally allocate resources within and between healthcare programmes when there is an exogenous budget and the parameters of the healthcare models are variable and uncertain. This formulation solves the optimal resource allocation problem and calculates the expected value of acquiring additional information to resolve the uncertainties within the allocation. It is shown that the proposed formulation has several advantages over the chance constrained and robust mathematical programming methods.     

Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line

Neuronal ubiquitin C-terminal hydrolase (UCH-L1) has been linked to Parkinson's disease (PD), the progression of certain nonneuronal tumors, and neuropathic pain. Certain lung tumor-derived cell lines express UCH-L1 but it is not expressed in normal lung tissue, suggesting that this enzyme plays a role in tumor progression, either as a trigger or as a response. Small-molecule inhibitors of UCH-L1 would be helpful in distinguishing between these scenarios. By utilizing high-throughput screening (HTS) to find inhibitors and traditional medicinal chemistry to optimize their affinity and specificity, we have identified a class of isatin O-acyl oximes that selectively inhibit UCH-L1 as compared to its systemic isoform, UCH-L3. Three representatives of this class (30, 50, 51) have IC(50) values of 0.80-0.94 micro M for UCH-L1 and 17-25 micro M for UCH-L3. The K(i) of 30 toward UCH-L1 is 0.40 micro M and inhibition is reversible, competitive, and active site directed. Two isatin oxime inhibitors increased proliferation of the H1299 lung tumor cell line but had no effect on a lung tumor line that does not express UCH-L1. Inhibition of UCH-L1 expression in the H1299 cell line using RNAi had a similar proproliferative effect, suggesting that the UCH-L1 enzymatic activity is antiproliferative and that UCH-L1 expression may be a response to tumor growth. The molecular mechanism of this response remains to be determined.     

Prediction of the critical micelle concentration in a lattice model for amphiphiles using a single-chain mean-field theory

A single-chain mean-field theory is used to predict the properties of binary surfactant solutions including the critical micelle concentration (cmc). In particular, the cmc of two symmetric nonionic amphiphiles is calculated as a function of temperature in order to analyze the validity of the ideal mixing assumption, often employed in the mass action model. On comparing against literature Monte Carlo results for the same lattice model we find that although it is applicable at low temperatures and hence cmcs at low amphiphile concentrations, at higher temperatures it becomes necessary to correct for the nonideal mixing of the free chain-free chain bulk interaction. We find that a simplistic model taking into account only the repulsive interaction is sufficient to restore the excellent quantitative agreement found between a single-chain mean-field theory calculations and literature molecular simulation results at the low temperature limit.     

Isolation,Identification and Pharmacological Effects of Mandragora autumnalis Fruit Flavonoids Fraction

Since ancient times, Mandragora autumnalis has been used as a traditional medicinal plant for the treatment of numerous ailments. In light of this, the current study was designed to isolate and identify the chemical constituents of the flavonoids fraction from M. autumnalis ripe fruit (FFM), and evaluate its DPPH scavenging, anti-lipase, cytotoxicity, antimicrobial and antidiabetic effects. An ethyl acetate extract of M. autumnalis was subjected to a sequence of silica gel column chromatography using different eluents with various polarities. The chemical structures of the isolated compounds were identified using different spectral techniques, including ¹H NMR and ¹³C NMR. FFM’s anti-diabetic activity was assessed using a glucose transporter-4 (GLUT4) translocation assay, as well as an inhibition against α-amylase and α-glucosidase using standard biochemical assays. The FFM anti-lipase effect against porcine pancreatic lipase was also evaluated. Moreover, FFM free radical scavenging activity using the DPPH test and antimicrobial properties against eight microbial strains using the micro-dilution method were also assessed. Four flavonoid aglycones were separated from FFM and their chemical structures were identified. The structures of the isolated compounds were established as kaempferol 1, luteolin 2, myricetin 3 and (+)-taxifolin 4, based on NMR spectroscopic analyses. The cytotoxicity test results showed high cell viability (at least 90%) for up to 1 mg/mL concentration of FFM, which is considered to be safe. A dose-dependent increase in GLUT4 translocation was significantly shown (p < 0.05) when the muscle cells were treated with FFM up to 0.5 mg/mL. Moreover, FFM revealed potent α-amylase, α-glucosidase, DPPH scavenging and porcine pancreatic lipase inhibitory activities compared with the positive controls, with IC₅₀ values of 72.44 ± 0.89, 39.81 ± 0.74, 5.37 ± 0.41 and 39.81 ± 1.23 µg/mL, respectively. In addition, FFM inhibited the growth of all of the tested bacterial and fungal strains and showed the greatest antibacterial activity against the K. pneumoniae strain with a MIC value of 0.135 µg/mL. The four flavonoid molecules that constitute the FFM have been shown to have medicinal promise. Further in vivo testing and formulation design are needed to corroborate these findings, which are integral to the pharmaceutical and food supplement industries.     

Regioselectivity in the Reactions of Bis-hydrazonoyl Halides with Pyrimidine-2-thiones

Summary.  Bis-hydrazonoyl chlorides react regioselectively with pyrimidine-2-thiones, which contain a masked thiourea residue, to give the hitherto unknown annelated 2,3-bis-arylhydrazono-thiazoles and 3,3′-bis-1,2,4-triazoles. Reaction of bis-hydrazonoyl chlorides with 2-methylthio derivatives gave only 3,3′-bis-1,2,4-triazoles. Received October 4, 2000. Accepted (revised) December 20, 2000     

Diels–Alder reactions and transformations of 2-cyclopenten-1-one with a chiral anthracene template

Excellent regio- and diastereoselectivity were achieved in the microwave assisted Diels–Alder reaction between (S)-9-(1-methoxyethyl) anthracene and 2-cyclopenten-1-one. The addition of Grignard reagents to the ketone cycloadduct gave poor levels of diastereoselectivity, however, the reduction was significantly more stereoselective. Flash vacuum pyrolysis of the reduced material furnished the corresponding allylic alcohol in good yield and ee.     

In vivo lipid diffusion coefficient measurements in rat bone marrow

The diffusion coefficient of lipids, D_l, within bone marrow, fat deposits and metabolically active intracellular lipids in vivo will depend on several factors including the precise chemical composition of the lipid distribution (chain lengths, degree of unsaturation, etc.) as well as the temperature. As such, D_l may ultimately prove of value in assessing abnormal fatty acid distributions linked to diseases such as cystic fibrosis, diabetes and coronary heart disease. A sensitive temperature dependence of D_l may also prove of value for MR-guided thermal therapies for bone tumors or disease within other fatty tissues like the breast. Measuring diffusion coefficients of high molecular weight lipids in vivo is, however, technically difficult for a number of reasons. For instance, due to the much lower diffusion coefficients compared to water, much higher b factors than those used for central nervous system applications are needed. In addition, the pulse sequence design must incorporate, as much as possible, immunity to motion, susceptibility and chemical shift effects present whenever body imaging is performed. In this work, high b-factor line scan diffusion imaging sequences were designed, implemented and tested for D_l measurement using a 4.7-T horizontal bore animal scanner. The gradient set available allowed for b factors as high as 0.03 μs/nm² (30,000 s/mm²) at echo times as short as 42 ms. The methods were used to measure lipid diffusion coefficients within the marrow of rat paws in vivo, yielding lipid diffusion coefficients approximately two orders of magnitude smaller than typical tissue water diffusion coefficients. Phantom experiments that demonstrate the sensitivity of lipid diffusion coefficients to chain length and temperature were also performed.     

Potential of membrane distillation in seawater desalination: Thermal efficiency,sensitivity study and cost estimation

In this work, an extensive analysis on direct contact membrane distillation (DCMD) performance was developed to estimate the mass flux and the heat efficiency, considering transport phenomena, membrane structural properties and most sensitive process parameters, with the aim to provide optimization guidelines for materials and methods. The results showed that an increase of the temperature gradient resulted in the enhancement of both transmembrane flux and thermal efficiency. The investigation of the effects of membrane properties confirmed that better DCMD performance was achieved when using polymeric membranes characterized by low thermal conductivity (flux and thermal efficiency declined by 26% and 50%, respectively, when increasing thermal conductivity from 0.1 to 0.5 W/m K), and high porosity. An optimal thickness value (around 0.7 mm) was identified when operating at low temperature gradient (<5 °C). However, at higher temperature gradient (>10 °C), increasing the membrane thickness from 0.25 to 1.55 mm resulted in a flux decay of about 70% without a significant improvement in thermal efficiency.     

Self‐Assembled Heteroleptic Zn(II) Dithiocarbamate‐Based 2D‐Interwoven Supramolecular Giant Macrocycles and Their Redox Properties

This article presents a new heteroleptic Zn(II) dithiocarbamate ( 1 ) having molecules linked together via H···H and π···π interactions to form a giant hexanuclear macrocycle. These macrocycles are connected together through S···H interactions to offer a unique two‐dimensional cloth‐like interwoven architecture in the solid state. The redox behavior of the complex deposited on the surface of a glassy carbon electrode was investigated in different pH media. The analyte was found to oxidize and reduce in a pH‐dependent irreversible manner. On the basis of the electrochemical findings, redox mechanistic pathways were proposed.