Protease sensors for bioimaging

Optical imaging of specific molecular targets and pathways in vivo has recently become possible through continued developments in imaging equipment, reconstruction algorithms, and more importantly the availability of imaging reporter molecules. These reporter molecules encompass photoproteins expressed in vivo and exogenously administered probes detectable by fluorescence and/or bioluminescence imaging. One particularly enticing aspect of optical imaging is the ability to design activatible probes with inherent amplification. This review summarizes our experience in developing novel near-infrared fluorescent (NIRF) imaging agents that report on protease activities. These agents are designed to be biocompatible, highly activatible, and able to produce bright NIRF following protease cleavage.     

Cyclization of Nitrospirobenzopyrans to Bridged Benzoxazepino[3,2-a]indoles

Condensation of 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with 5-nitrosalicylaldehyde afforded 1′-[(N-monosubstituted carbamoyl)methyl]indoline nitrospirobenzopyrans. Treatment of the latter with strong base led to the formation of a mixture of cis/trans-5a,13-methano-1,3-benzoxazepino[3,2-a]indoles. Results of semiempirical calculations gave evidence that such a transformation of nitrospirobenzopyrans to bicyclic indole derivatives could proceed via a single transition state, where the negatively charged carbon atom attacks the vinylic double bond of the spiropyran system.     

Synthesis and antibacterial activity of 7-ethyl-3-methyl-4,7-dihydro-4-oxoisothiazolo[5,4-b]pyridine-5-carboxylic acid

The synthesis of the quinolone, 7-ethyl-3-methyl-4,7-dihydro-4-oxoisothiazolo[5,4-b]pyridine-5-carboxylic acid 4 was accomplished utilizing the Gould-Jacobs dependent route. The compound had very weak in vitro activity as compared to nalidixic acid versus E. coli, P. aeruginosa, K. pnuemoniae, S. aureus and P. mirabilis.     

An efficient synthesis of 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid and some carbonyl derivatives of it and its 6-acetyl homologue

Starting with 1,1-dimethoxy-2-propanone ( 1 ), 6-formyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5a ) has been prepared in large quantities by a highly efficient, 4-step synthesis. This compound, along with its one carbon homologue, 6-acetyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid ( 5b ) has been reacted with several carbonyl derivative forming reagents to provide a series of side chains for β-lactams. Among these carbonyl derivatives are styrylamides which were prepared from Wittig and Horner-Emmons reagents. The preparation of the phosphonium salts and phosphonate esters is also described.     

A CONVENIENT IRRADIATION CELL FOR FERRIOXALATE ACTINOMETRY

Abstract— A calibrated volumetric optical cuvette is described which both simplifies the technique and improves the precision of potassium ferrioxalate actinometry. The cuvette is used both for irradiation of the actinometer solution and for in situ dilution and chemical developing of the irradiated aliquot. The technique permits all but one manipulation to be carried out in total darkness, thus protecting the actinometer solutions from ambient light. The method can be extended to any actinometric procedure and the volumetric cuvettes are very useful in a variety of other spectrophotometric applications.     

Design and characterization of flow-through coulometric cells with porous working electrodes made of crushed vitreous carbon

Summary Three types of flow-through, three-electrode cells with porous working electrodes made of crushed vitreous carbon were tested. The electrochemical properties of the cells were studied by hydrodynamic and cyclic voltammetry using potassium ferrocyanide test solutions. Depending on the volume of the porous working electrode, Nernstian behaviour and electrochemical yields up to 100% were observed for flow rates 1 to 7 ml/min. In the stopped-flow regime the cells exhibit thin-layer cell properties. The utility of the cells is demonstrated for on-line coulometric detection, continuous removal of impurities and dissolved oxygen and for anodic stripping coulometry of trace copper.On leave from: Department of Analytical Chemistry, Slovak Technical University, CS-812 37 Bratislava, Czechoslovakia     

Stereoselective synthesis of (E)-beta-tributylstannyl-alpha,beta-unsaturated ketones: construction of a key intermediate for the total synthesis of zoanthamine

(E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of zoanthamine, a structurally complex marine natural product.     

Magnetic structure of the europium fulleride ferromagnet Eu(6)C(60)

The powder neutron diffraction technique has been used for the direct observation of magnetic scattering below a Curie temperature of approximately 14 K in the fullerene-based molecular ferromagnet Eu6C60. Europium is in the divalent state with a magnetic moment of 7.1(3) muB per atom, and the configurational symmetry of the magnetic structure is body-centered cubic. Close contacts between Eu2+ and neighboring C60 units provide the signature of orbital hybridization, which can evidently account for the conducting and magnetic properties of the material.     

Production of poly(methyl methacrylate) particles by dispersion polymerization with mercaptopropyl terminated poly(dimethylsiloxane) stabilizer in supercritical carbon dioxide

Poly(methyl methacrylate) (PMMA) particles were produced by dispersion polymerization of methyl methacrylate in the presence of mercaptopropyl terminated poly(dimethylsiloxane) (MP-PDMS) in supercritical carbon dioxide at about 30 MPa for 24 h at 65 °C. The particle diameter could be controlled in a size range of submicron to micron by varying MP-PDMS concentration. The MP-PDMS worked as not only a chain transfer agent but also a colloidal stabilizer, which was named tran stab.Part CCLI of the series Studies on suspension and emulsion     

Molecular Rectangle Formed by Head-to-tail Self-Assembly of 1-(Dipyrrin-2-yl)-1-(dipyrrin-3-yl)methane

Summary. 1-(Dipyrrin-2-yl)-1-(dipyrrin-3-yl)methane, the N-confused analog of biladiene-ac, is prepared by condensation of 2,3-dipyrromethane with two molecules of 2-formylpyrrole in dichloromethane in the presence of hydrogen bromide. Self-assembly of the ligand with Zn(II) in dichloromethane and methanol offers a dinuclear dimeric complex with a ligand:metal ratio of 2:2. X-Ray crystal structure analysis reveals two ligands bound through a head-to-tail pattern to two zinc centers to form a severely distorted helical conformation, which has the shape of a rectangle.