Novel fluorescent biosensor for pathogenic toxins using cyclic polypeptide conjugates

This work describes a two-step conjugate synthesis of a new fluorescent analog of microcystin-LR and its subsequent utilization for the development of an optical biosensor for cyanobacteria toxins. The biosensor concept is based on the competitive binding between the native microcystin and its fluorescent analog at immobilized alkaline phosphatase enzymes.     

Hybrid solar cells using nanorod zinc oxide electrodes and perylene monoimide–monoanhydride dyes

Hybrid solar cells have been fabricated using perylene monoimide–monoanhydride dyes with nanorod zinc oxide electrodes as electron transporting layers. We have investigated the influence of the spacer alkyl chain length of perylene monoimide–monoanhydride (PMIMA) dyes on the device performance in hybrid solar cells using nanorod zinc oxide electrodes. Nanorod zinc oxide electrodes with 50–150 nm of diameter were synthesized in the presence of PEG400 by using microwave heating method. We observed that the dyes with longer and brunched alkyl chains exhibit higher efficiencies in hybrid solar cells. We report the highest efficiency obtained with zinc oxide nanorods under standard conditions for perylene monoimide–monoanhydride derivative with PMIMA_1 that performs 400 mV open circuit voltage, 2.81 mA/cm² short-circuit current and 0.59% overall conversion efficiency.     

Analysis of five HMG-CoA reductase inhibitors-- atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin: pharmacological, pharmacokinetic and analytical overview and development of a new method for use in pharmaceutical formulations analysis and in vitro metabolism studies

A specific, accurate, precise and reproducible high-performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous quantitation of five 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, viz. atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin, in pharmaceutical formulations and extended the application to in vitro metabolism studies of these statins. Ternary gradient elution at a flow rate of 1 mL/min was employed on an Intertisl ODS 3V column (4.6 x 250 mm, 5 microm) at ambient temperature. The mobile phase consisted of 0.01 m ammonium acetate (pH 5.0), acetonitrile and methanol. Theophylline was used as an internal standard (IS). The HMG-CoA reductase inhibitors and their metabolites were monitored at a wavelength of 237 nm. Drugs were found to be 89.6-105.6% of their label's claim in the pharmaceutical formulations. For in vitro metabolism studies the reaction mixtures were extracted with simple liquid-liquid extraction using ethyl acetate. Baseline separation of statins and their metabolites along with IS free from endogenous interferences was achieved. Nominal retention times of IS, atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin were 7.5, 17.2, 21.6, 28.5, 33.5 and 35.5 min, respectively. The proposed method is simple, selective and could be applicable for routine analysis of HMG-CoA reductase inhibitors in pharmaceutical preparations as well as in vitro metabolism studies.     

Nonlinear Elasticity in a Deforming Ambient Space

In this paper, we formulate a nonlinear elasticity theory in which the ambient space is evolving. For a continuum moving in an evolving ambient space, we model time dependency of the metric by a time-dependent embedding of the ambient space in a larger manifold with a fixed background metric. We derive both the tangential and the normal governing equations. We then reduce the standard energy balance written in the larger ambient space to that in the evolving ambient space. We consider quasi-static deformations of the ambient space and show that a quasi-static deformation of the ambient space results in stresses, in general. We linearize the nonlinear theory about a reference motion and show that variation of the spatial metric corresponds to an effective field of body forces.     

Selective Structural Derivatization of Flavonoid Acetamides Significantly Impacts Their Bioavailability and Antioxidant Properties

Flavonoids show abundant favorable physicochemical and drug related properties, leading to substantial biological applications which are limited by undesirable properties such as poor solubility, high polarity, low bioavailability, and enzymatic degradations. Chemical modification with bioisosteres can be used to address some of these challenges. We report the synthesis and characterization of partial flavonoid acetamide derivatives from quercetin, apigenin and luteolin and the evaluation of their structure-activity relationships based on antioxidant, bioavailability, drug likeness, and toxicity properties. The sequential synthesis was achieved with 76.67–87.23% yield; the structures of the compounds were confirmed using ¹H & ¹³C NMR characterizations. The purity of each compound was determined by HPLC while the molecular weights were determined by mass spectrometry. The % bioavailability was determined using the dialysis tubing procedure and the values were in the range 15.97–38.12%. The antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and expressed as the IC₅₀ values which were in the range 31.52–198.41 µM. The drug likeness and the toxicity properties of compounds 4, 5, 7, 11 and 15 were predicted using computational tools and showed satisfactory results. A structure-activity relationship evaluation reveals that hydroxyl and methylene groups attached on the 2-phenylchromen-4-one structure of the flavonoid play a colossal role in the overall antioxidant and bioavailability properties. The improved bioavailability and excellent drug relevance and toxicity properties present flavonoid acetamide derivatives as prospective drug candidates for further evaluations.     

The behavior of lipid debris left on cell surfaces from microbubble based ultrasound molecular imaging

Lipid monolayer coated microbubbles are currently being developed to identify vascular regions that express certain surface proteins as part of the new technique of ultrasound molecular imaging. The microbubbles are functionalized with targeting ligands which bind to the desired cells holding the microbubbles in place as the remaining unbound microbubbles are eliminated from circulation. Subsequent scanning with ultrasound can detect the highly reflectant microbubbles that are left behind. The ultrasound scanning and detection process results in the destruction of the microbubble, creating lipid fragments from the monolayer. Here we demonstrate that microbubbles targeted to 4T1 murine breast cancer cells and human umbilical cord endothelial cells leave behind adhered fragments of the lipid monolayer after exposure to ultrasound with peak negative pressures of 0.18 and 0.8 MPa. Most of the observed fragments were large enough to be resistant to receptor mediated endocytosis. The fragments were not observed to incorporate into the lipid membrane of the cell over a period of 96 min. They were not observed to break into smaller pieces or significantly change shape but they were observed to undergo translation and rotation across the cell surface as the cells migrated over the substrate. These large fragments will apparently remain on the surface of the targeted cells for significant periods of time and need to be considered for their potential effects on blood flow through the microcapillaries and potential for immune system recognition.     

Pressure assisted chelating extraction: a novel technique for digesting metals in solid matrices

This work describes a novel technique for the digestion of metals in solid matrices. The technique is called pressure assisted chelating extraction (PACE). In a typical procedure, a solid sample is placed in a stainless steel cell and is mixed with appropriate chelating agents. Using a programmed sequence of temperature, static time, pressure and thermal equilibration available in ASE 200, the metal is removed under moderate temperature (up to 200 degrees C) and pressure (up to 3000 psi). PACE achieves metal recovery that is equivalent to that of wet digestion techniques and also provides for a clean and safe operation by substituting the strong acids commonly used during wet digestion with chelating agents. It uses less solvents and significantly less time (minutes vs. hours) for metal digestion. PACE has been validated using certified standard reference materials (SRMs) including industrial sludge, buffalo river sediments and coal fly ash. The total time required to remove metals was approximately 20 min. Results show that the PACE system provides an ideal platform for efficient, rapid, and safe metal digestion. Good agreement between measured and reference values for Pb, Mn, and Cu were found with recoveries averaging between 80 and 101% and a relative standard deviation of less than 5%. This approach may provide an alternative digestion technique for environmental samples, alloys, biological materials and samples of geological importance. The potential advantage offered lies in non-destruction of the sample, automation and the exclusion of concentrated mineral acids during the digestion procedure.     

New proton-ionizable macrocyclic compounds containing one and two triazole subcyclic units — synthesis and complexation properties

A series of new macrocyclic compounds containing one and two proton-ionizable triazole subcyclic units have been prepared and characterized. These triazolo-crowns containing benzo, tert-butylbenzo or cyclohexano lipophilic groups show varying solubilities in chloroform. The bistriazolo-crowns dissolved in chloroform are highly effective for extraction of lead, mercury, and gold from aqueous solutions.     

Synthesis of lariat ethers with pendent amine,amide, O‐benzylhydroxamate,and urethane groups

Synthetic routes to twenty‐six new crown ether compounds with pendent amine, amide, O‐benzylhydrox‐amate, and urethane groups are reported. The new lariat ether compounds are based on sym‐dibenzo‐16‐crown‐5, sym‐dicyclohexano‐16‐crown‐5, and 14‐crown‐4 scaffolds.