Technetium(III), Technetium(II), and Technetium(I) Complexes with Pyridine Ligands. Can Pyridine Coordination Stabilize the Low Oxidation States of Technetium?

The substitution chemistry of TcCl(3)(PPh(3))(2)(CH(3)CN) is rather facile relative to the analogous rhenium complex, since both the chloride and phosphine ligands are easily substituted for various pyridine ligands. Consequently a series of Tc(III) complexes with amine, pyridine, and polypyridyl ligands were prepared and characterized by (1)H NMR and cyclic voltammetry. In addition, the zinc reduction of TcCl(4)(py)(2) in the presence of pyridine results in TcCl(2)(py)(4). Structural and spectroscopic data indicate that this Tc(II) complex exhibits strong metal-pyridine interactions characteristic of low-valent amine complexes of Re(II) and Os(II). For example, a decrease of 0.04 and 0.06 ? is observed for the trans-Tc-N bond length in TcCl(2)(py)(4 )relative to mer-TcCl(3)(pic)(3) and [TcCl(2)(py)(3)(PPh(3))](+), respectively. This ability of pyridine to function both as a strong sigma-donor and moderate pi-acid ligand has resulted in the isolation of technetium complexes in various oxidation states with similar ligand environments. As a result, a structural comparison of [TcCl(2)(py)(3)(PPh(3))](+), TcCl(2)(py)(4), TcCl(tpy)(py)(2), and other known Tc(III) and Tc(II) pyridine complexes is presented. Crystals of [TcCl(2)(py)(3)(PPh(3))]PF(6) are triclinic, with space group P&onemacr;, Z = 2, and lattice parameters a = 12.677(4) ?, b = 13.064(4) ?, c = 13.103(5) ?, alpha = 110.14(3) degrees, beta = 101.12(3) degrees, gamma = 96.61 degrees, V = 1959 ?(3), and R = 0.0615 (R(w) = 0.1148). Crystals of TcCl(2)(py)(4) are tetragonal, with space group I4(1)/acd, Z = 8, and lattice parameters a = 15.641(4) ?, c = 16.845(6) ?, V = 4121 ?(3), and R = 0.0373 (R(w) = 0.0290). Crystals of TcCl(tpy)(py)(2) are orthorhombic, with space group C222(1), Z = 4, and lattice parameters a = 9.359(3) ?, b = 16.088(6) ?, c = 18.367(4) ?, V = 2765 ?(3), and R = 0.0499 (R(w) = 0.0599).     

Asymmetric Michael addition of glycine imines via quaternary ammonium ion catalysis

The asymmetric Michael addition of glycine imine esters to simple α,β-unsaturated ketones via PTC is investigated. It is found that by employing 1 mol % of a chiral quaternary ammonium salt, derived from α-methylnaphthylamine in conjunction with Cs₂CO₃, high enantioselectivities can be obtained in conjugate additions involving simple alkylvinylketones.     

Ultrasensitive small molecule fluorogenic probe for human heparanase

Heparanase (HPA) is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as various types of cancer and inflammation. The detection of heparanase enzymatic activity holds tremendous value in the study of the cellular microenvironment, and search of molecular therapeutics targeting heparanase, however, no structurally defined probes are available for the detection of heparanase activity. Here we present the development of the first ultrasensitive fluorogenic small-molecule probe for heparanase enzymatic activity via tuning the electronic effect of the substrate. The probe exhibits a 756-fold fluorescence turn-on response in the presence of human heparanase, allowing one-step detection of heparanase activity in real-time with a picomolar detection limit. The high sensitivity and robustness of the probe are exemplified in a high-throughput screening assay for heparanase inhibitors.

Heparanase, a critical enzyme involved in the remodeling of the extracellular matrix, activates a disaccharide probe HADP to give a strong fluorescence signal.     

Synthesis of alpha-fluorosulfonamides by electrophilic fluorination

Alpha-fluorosulfonamides were prepared by electrophilic fluorination of tertiary sulfonamides using N-fluorobenzenesulfonimide as fluorinating agent and utilizing the dimethoxybenzyl group (DMB) as a new sulfonamide protecting group. Removal of the DMB group with TFA/CH(2)Cl(2) gave primary and secondary alpha-fluorosulfonamides.     

High-performance liquid chromatographic analysis of vancomycin in plasma, bone, atrial appendage tissue and pericardial fluid

Solid-phase extraction coupled with reversed-phase high-performance liquid chromatography and UV detection was employed for the analysis of the antibiotic vancomycin in patient plasma, bone, atrial appendage, and pericardial fluid. Vancomycin was quantitated in samples from patients undergoing cardiac surgery. Calibrations were linear in the range 3-100 micrograms/ml vancomycin; the lower limit of detection was approximately 3 micrograms/ml in fluids with an absolute limit of detection in bone samples of 0.75 microgram per injection.     

α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine

Despite being relatively benign and not an indicative signature of toxicity, fibril formation and fibrillar structures continue to be key factors in assessing the structure–function relationship in protein aggregation diseases. The inability to capture molecular cross-talk among key players at the tissue level before fibril formation greatly accounts for the missing link toward the development of an efficacious therapeutic intervention for Type II diabetes mellitus (T2DM). We show that human α-calcitonin gene-related peptide (α-CGRP) remodeled amylin fibrillization. Furthermore, while CGRP and/or amylin monomers reduce the secretion of both mouse Ins1 and Ins2 proteins, CGRP oligomers have a reverse effect on Ins1. Genetically reduced Ins2, the orthologous version of human insulin, has been shown to enhance insulin sensitivity and extend the life-span in old female mice. Beyond the mechanistic insights, our data suggest that CGRP regulates insulin secretion and lowers the risk of T2DM. Our result rationalizes how migraine might be protective against T2DM. We envision the new paradigm of CGRP : amylin interactions as a pivotal aspect for T2DM diagnostics and therapeutics. Maintaining a low level of amylin while increasing the level of CGRP could become a viable approach toward T2DM prevention and treatment.

CGRP concentration is elevated in migraine conditions. The protective effect of migraine against type 2 diabetes is attributed to the ability of CGRP to remodel human amylin aggregation and to suppress the secretion of mouse insulin 2 (the orthologue of human insulin).     

Lead hopping using SVM and 3D pharmacophore fingerprints

The combination of 3D pharmacophore fingerprints and the support vector machine classification algorithm has been used to generate robust models that are able to classify compounds as active or inactive in a number of G-protein-coupled receptor assays. The models have been tested against progressively more challenging validation sets where steps are taken to ensure that compounds in the validation set are chemically and structurally distinct from the training set. In the most challenging example, we simulate a lead-hopping experiment by excluding an entire class of compounds (defined by a core substructure) from the training set. The left-out active compounds comprised approximately 40% of the actives. The model trained on the remaining compounds is able to recall 75% of the actives from the "new" lead series while correctly classifying >99% of the 5000 inactives included in the validation set.     

Volatilization of Pesticides from Plant and Soil Surfaces—Field Versus Laboratory Experiments

Abstract

Comparative volatilization experiments were carried out using isoproturon and parathion-methyl sprayed on French beans in field experiments and on plant stands (0.5 m²) in the volatilization chamber developed by the SLFA Neustadt using both compounds ¹⁴C-labelled. The experimental conditions in the field experiments concerning wind speed, temperature and humidity fluctuations were simulated in the volatilization chamber. The laboratory experiment reflected the actual outdoor situation, showing only a negligible amount of volatile isoproturon directly measured in air samples, and providing no reduction of the A.I. residues in plants compared with the initial value in the corresponding field experiment. 77.2% of the parathion-methyl applied to the plants were volatilized and measured directly in air samples in the volatilization chamber while a reduction by 74.7% was found for the corresponding field experiment by residue analysis of the plants after 24 h. No details could be given concerning the nature of the evaporated portions in the field experiment.     

2-Butyl-4-iodoimidazole-5-carboxaldehyde: A Versatile Intermediate for the Synthesis of Highly Functionalized Imidazoles

The facile preparation of 2-butyl-4-iodoimidazole-5-carboxaldehyde 1 is described. The versatility of this intermediate in the synthesis of highly tunctionalized imidazoles is demonstrated with the synthesis of two potent and selective angiotensin II receptor antagonists.     

Simulation of a mixed-conducting membrane-based gas turbine power plant for CO<Subscript>2</Subscript> capture: system level analysis of operation stability and individual process unit degradation

A gas turbine power plant for CO₂ capture, based on oxygen-permeable membranes with mixed ionic-electronic conductivity, was analysed with respect to long-term stability by means of numerical simulation. Due to the attractive transport and physicochemical properties of mixed-conducting La₂NiO_4+δ, this nickelate was selected as a prototype membrane material for this application. Experiments showed very slow degradation of La₂NiO_4+δ membranes at oxygen chemical potentials close to atmospheric conditions, which are associated with kinetic demixing and other microstructure-related factors. Interaction with CO₂ in the intermediate temperature range also leads to lower oxygen permeation, whilst increasing oxygen pressure may cause partial phase decomposition and microstructural changes, thus again limiting the range of possible operation conditions. The relevant operational constraints were included in a detailed membrane-based gas turbine power plant model. The membrane performance degradation with time was approximated by a linear function with average rate of 3.3% per 1,000 operation hours. Furthermore, performance deterioration of the gas turbine compressor and turbine were also considered. Simulations revealed that the power plant is substantially affected by degradation of the ceramic membranes and turbomachinery components. The already rather small operating window was further narrowed when compared with a conventional gas turbine power plant. Two different designs of the membrane-based power plant were analysed: (1) with and (2) without additional combustors (afterburners) between the membrane reactor and the gas turbine. Afterburners increase thermal efficiency as well as power output, but also lead to non-negligible CO₂ emissions. In order to have a frame of comparison, results for a conventional gas turbine power plant with degradation of turbomachinery components are also presented. Simulations representing changes in ambient temperature and fuel composition as well as failure incidents were executed to analyse the susceptibility of the gas turbine power plant to external and internal changes.