2-dimensional analytic approach for anion differentiation with chromofluorogenic receptors

By linking the urea moiety at the 1,8 positions of the carbazole fragment, we synthesized host systems 1, 2, and 3 having both chromogenic and fluorogenic signaling subunits. The spectral changes in both the signaling subunits could be easily analyzed via a simple 2-dimensional (2D) analytic approach described here, which enables us to differentiate the given set of anions. Structural studies are also reported.     

Chelation of vanadium(V) by difluoromethylene bisphosphonate, a structural analogue of pyrophosphate

The structural and functional analogy between difluoromethylene bisphosphonate (CF2PP) and pyrophosphate (PPi) is investigated in a reaction with V(V) in the form of vanadate. The reaction of CF2PP with vanadate was investigated using 1.00 M KCl as supporting electrolyte over the ranges 3 < or = [CF2PP] < or = 60 mM and 2.06 < or = pH < or = 11.80. 51V, 19F, and 31P NMR spectroscopic studies showed that a 1:1 species was formed with an H+-dependent formation constant of 110 M-1 at pH 7.22. Results of solution experiments and ab initio calculations are consistent with CF2PP coordinating V(V) in a bidentate manner, as previously reported for PPi. Below pH 4, a minor complex forms, which is consistent with a 1:2 stoichiometry. This complex was also observed with pyrophosphate. The X-ray crystal structure of the monoprotonated difluoromethylene bisphosphonate anion (H[CF2PP]3-)-toludine complex is presented. The H[CF2PP]3- anion crystallized in the triclinic space group P with a = 12.7629(7) A, b = 13.3992(7) A, c = 17.1002(9) A, and V = 2584.4(2) A3, and Z = 2. Sheets of the layers of anions are connected through a network of H-bonds and separated by a layer of toludine cations. The structural features are investigated, and the CF2PP anion was found to be longer and wider than the corresponding PPi. Given the larger size of this anion compared to PPi, the chelation affinity upon CF2 substitution was found to be 4-5-fold reduced at neutral pH.     

A gamma-spectrometric method for the determination of plutonium isotope ratios

A gamma-spectrometric method using an intrinsic high resolution germanium detector has been developed for the determination of isotope ratios of plutonium from samples in solution form. The method is based on the assay of low energy gamma-rays of²³⁸Pu,²³⁹Pu,²⁴⁰Pu and²⁴¹Pu and does not require the use of branching intensities or the knowledge of detection efficiencies for different gamma rays. Since low energy gamma-rays are used, the effect of²⁴¹Am has also been studied. It is found that results are not affected up to 0.5 wt% of²⁴¹Am in plutonium samples. An accuracy of 3% is achievable in the determination of²⁴⁰Pu/²³⁹Pu and²⁴¹Pu/²³⁹Pu atom ratios as demonstrated by carrying out measurements on isotopic standards of plutonium.     

Expected and unexpected results from combined beta-hairpin design elements

A model beta-hairpin dodecapeptide [EFGWVpGKWTIK] was designed by including a favorable D-ProGly Type II' beta-turn sequence and a Trp-zip interaction, while also incorporating a beta-strand unfavorable glycine residue in the N-terminal strand. This peptide is highly folded and monomeric in aqueous solution as determined by combined analysis with circular dichroism and 1H NMR spectroscopy. A peptide representing the folded conformation of the model beta-hairpin [cyclic(EFGWVpGKWTIKpG)] and a linear peptide representing the unfolded conformation [EFGWVPGKWTIK] yield unexpected relative deviations between the CD and 1H NMR spectroscopic results that are attributed to variations in the packing interactions of the aromatic side chains. Mutational analysis of the model beta-hairpin indicates that the Trp-zip interaction favors folding and stability relative to an alternate hydrophobic cluster between Trp and Tyr residues [EFGYVpGKWTIK]. The significance of select diagonal interactions in the model beta-hairpin was tested by rearranging the cross-strand hydrophobic interactions to provide a folded peptide [EWFGIpGKTYWK] displaying evidence of an unusual backbone conformation at the hydrophobic cluster. This unusual conformation does not appear to be a result of the glycine residue in the beta-strand, as replacement with a serine results in a peptide [EWFSIpGKTYWK] with a similar and seemingly characteristic CD spectrum. However, an alternate arrangement of hydrophobic residues with a Trp-zip interaction in a similar position to the parent beta-hairpin [EGFWVpGKWITK] results in a folded beta-hairpin conformation. The differences between side chain packing of these peptides precludes meaningful thermodynamic analysis and illustrates the caution necessary when interpreting beta-hairpin folding thermodynamics that are driven, at least in part, by aromatic cross strand interactions.     

Lewis Acid Catalyzed Condensation–Cyclization Cascade: Direct Synthesis of Di/Trifluoromethyl‐1,2,3,4‐tetrahydroquinazolines

Condensed heterocycles such as quinazolines constitute the framework of many promising drugs. The great impact of the dramatic fluorine effect in pharmaceuticals prompted a great surge in the quest for fluorinated drug design resulting in over 20 % fluorine‐containing drugs in the market today. Therefore, finding an efficient and cost‐effective method for the direct synthesis of fluorine‐tagged quinazoline systems is of great significance in the pharmaceutical arena. For the first time, a one‐pot sequential condensation–cyclization reaction to form selectively the difluoro/trifluoromethylated tetrahydroquinazolines from simple components difluoro/trifluoroacetaldehyde hemiacetal and aromatic amines is reported. Our recent studies using difluoro/trifluoroacetaldehyde hemiacetal as simple and elegant difluoro/trifluoromethyl synthons and metal triflates such as gallium triflate as safe and stable Lewis acid catalysts led us to this direct synthesis protocol for the expedient and convenient synthesis of fluorinated quinazolines. DFT calculations at PCM/B3LYP/6‐31++G** were carried out for evaluating a possible reaction mechanism for this cyclization. According to the DFT calculations, product stereochemistry is thermodynamically driven, favoring the cis isomer as the major product, which is also confirmed experimentally.     

Determination of oxytocin in milk of cows administered oxytocin

To address people's concerns of exogenous oxytocin (OT) administration to lactating bovines, a study was undertaken to (a) establish an enzyme immunoassay (EIA) for OT determination in milk, (b) quantify OT in milk of cows administered OT, and (c) study influence of pasteurization on OT stability in milk. A sensitive EIA validated according to the criteria of European Union—Decision 2002/657/EC was developed for OT in skim milk in an analytical range of 10-250 pg mL⁻¹ with a decision limit (CCα) of 30 pg mL⁻¹ and detection capability (CCβ) of 41.5 pg mL⁻¹. Milk samples collected from cows (n = 38) administered either 25 or 50 IU OT prior to milking were investigated for the presence of OT. There was no significant difference among both groups with the mean concentrations of OT being 15.8 and 14.9 pg mL⁻¹ for cows subjected to 25 and 50 IU OT administration, respectively. The OT levels in skim milk of control cows (n = 30; untreated) were basal (around 10 pg mL⁻¹). All the analyzed milk samples were below the CCα value of 30 pg mL⁻¹. Pasteurization of OT spiked milk samples at different temperature and sample holding conditions reduced the immunological activity of OT to 43% at 110 °C. However, no further decline occurred in the immunological activity with increased pasteurization temperature and time. It was concluded that the milk OT concentrations after OT administrations were minimal and below the assay decision limit. However, OT was quite stable to pasteurization in OT spiked milk.     

Recent developments in the synthesis of five- and six-membered heterocycles using molecular iodine

Heterocyclic scaffolds represent the key structural subunits of many biologically active compounds. Over the last few years iodine-mediated reactions have been extensively studied due to their low cost and eco-friendliness. This Review covers advances in the field of iodine-mediated synthesis of heterocyclic compounds since 2006, especially with an emphasis on mechanisms of ring formation. In this article, syntheses of different heterocycles are classified based on the manipulation of functional groups.     

Determination of organophosphate pesticides at a carbon nanotube/organophosphorus hydrolase electrochemical biosensor

An amperometric biosensor for oganophosphorus (OP) pesticides based on a carbon nanotube (CNT)-modified transducer and an organophosphorus hydrolase (OPH) biocatalyst is described. A bilayer approach with the OPH layer atop of the CNT film was used for preparing the CNT/OPH biosensor. The CNT layer leads to a greatly improved anodic detection of the enzymatically generated p-nitrophenol product, including higher sensitivity and stability. The sensor performance was optimized with respect to the surface modification and operating conditions. Under the optimal conditions the biosensor was used to measure as low as 0.15 μM paraoxon and 0.8 μM methyl parathion with sensitivities of 25 and 6 nA/μM, respectively.     

Preparation and characterization of hydroxypropyl-β-cyclodextrin inclusion complex of eugenol: differential pulse voltammetry and (1)H-NMR

The objective of present investigation was to improve the solubility of Eugenol by preparing the inclusion complex of Eugenol with hydroxypropyl-β-cyclodextrin (Hp-β-CD) and characterize the prepared complex by using NMR and differential pulse voltammetry (DPV). Phase solubility curve was plotted using Hp-β-CD in ranging from 0-40 mM of Hp-β-CD and found to be linear. Therefore, inclusion complex was prepared in equimolar ratio of Eugenol and Hp-β-CD by lyophilization method. Fourier transform infrared spectroscopy (FT-IR), (1)H-NMR and DPV were performed for Eugenol, Hp-β-CD and prepared inclusion complex of Eugenol. 2D (two dimensional) NMR was also performed for prepared inclusion complex. The proton of phenol moiety of Eugenol experienced a pronounced chemical shift variation in (1)H-NMR. The positive sign of the variation for proton in (1)H-NMR indicated that the proton was located near to an oxygen atom in the Hp-β-CD cavity and its magnitude showed a strong interaction between -OH proton of Eugenol and Hp-β-CD. 2D NMR confirms the interaction between phenolic group and hydrogen atoms of Hp-β-CD. A well defined anodic peak current corresponding to oxidation of Eugenol in non-encapsulated and Hp-β-CD-Eugenol inclusion complex in phosphate buffer (pH 6.8) was obtained at about 0.35 V and 0.40 V, respectively. The positive shift in oxidation potential indicated the formation of complex via hydrophobic interactions. The oxidant power of Eugenol was retained in complex form as indicated by DPV results. Thus, its oxidation dependent pharmacological property such as antimicrobial activity is not affected after complexation with Hp-β-CD. Thus, (1)H-NMR, 2D-NMR and DPV techniques can be used as valuable tools to determine the mechanism of complexation and state of electrochemical active drug in inclusion complex.     

Green Synthesis of Silver Nanoparticles Using Water Extract from Galls of <Emphasis Type="Italic">Rhus Chinensis</Emphasis> and Its Antibacterial Activity

The green synthesis of silver nanoparticles (AgNPs) has been proposed as a simple, eco-friendly and cost effective alternative to chemical and physical methods. The Rhus chinensis plant is one of the well studied medicinal plant and its galls find excellent clinical and therapeutic applications. The present study reports the use of water extract from galls of R. chinensis as a reducing agent and formation of AgNPs from silver nitrate solution by a green synthesis route. The AgNPs formation was observed visually by color change and the absorbance peak at 450 nm was observed by UV–Visible spectrophotometer. The shape, size, and morphology of synthesized AgNPs were monitored by transmission electron microscopy and field-emission scanning electron microscopy. The face centered cubic structure of AgNPs was confirmed by X-ray diffraction pattern and element composition by energy dispersive X-ray analysis. The Fourier transform infrared spectroscopy spectrum revealed that the presence of components acts as a reducing and capping agent. The antibacterial activity was performed using the agar well diffusion method. Minimum inhibitory concentration and minimum bactericidal concentration were determined by broth dilution and spread plate method respectively. Synthesized nanoparticles were spotted as triangular and hexagonal shape and the particle size was around 150 nm.