Importance of sialic acid residues illuminated by live animal imaging using phosphorylcholine self-assembled monolayer-coated quantum dots

Glycans are expected to be one of the potential signal molecules for controlling drug targeting/delivery or long-term circulation of biopharmaceuticals. However, the effect of the carbohydrates of artificially glycosylated derivatives on in vivo dynamic distribution profiles after intravenous injection of model animals remains unclear due to the lack of standardized methodology and a suitable platform. We report herein an efficient and versatile method for the preparation of multifunctional quantum dots (QDs) displaying common synthetic glycosides with excellent solubility and long-term stability in aqueous solution without loss of quantum yields. Combined use of an aminooxy-terminated thiol derivative, 11,11'-dithio bis[undec-11-yl 12-(aminooxyacetyl)amino hexa(ethyleneglycol)], and a phosphorylcholine derivative, 11-mercaptoundecylphosphorylcholine, provided QDs with novel functions for the chemical ligation of ketone-functionalized compounds and the prevention of nonspecific protein adsorption concurrently. In vivo near-infrared (NIR) fluorescence imaging of phosphorylcholine self-assembled monolayer (SAM)-coated QDs displaying various simple sugars (glyco-PC-QDs) after administration into the tail vein of the mouse revealed that distinct long-term delocalization over 2 h can be achieved in cases of QDs modified with α-sialic acid residue (Neu5Ac-PC-QDs) and control PC-QDs, while QDs bearing other common sugars, such as α-glucose (Glc-PC-QDs), α-mannose (Man-PC-QDs), α-fucose (Fuc-PC-QDs), lactose (Lac-PC-QDs), β-glucuronic acid (GlcA-PC-QDs), N-acetyl-β-D-glucosamine (GlcNAc-PC-QDs), and N-acetyl-β-D-galactosamine (GalNAc-PC-QDs) residues, accumulated rapidly (5-10 min) in the liver. Sequential enzymatic modifications of GlcNAc-PC-QDs gave Galβ1,4GlcNAc-PC-QDs (LacNAc-PC-QDs), Galβ1,4(Fucα1,3)GlcNAc-PC-QDs (Le(x)-PC-QDs), Neu5Acα2,3Galβ1,4GlcNAc-PC-QDs (sialyl LacNAc-PC-QDs), and Neu5Acα2,3Galβ1,4(Fucα1,3)GlcNAc-PC-QDs (sialyl Le(x)-PC-QDs) in quantitative yield as monitored by direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry analyses. Live animal imaging uncovered for the first time that Le(x)-PC-QDs also distributed rapidly in the liver after intravenous injection and almost quenched over 1 h in similar profiles to those of LacNAc-PC-QDs and Lac-PC-QDs. On the other hand, sialyl LacNAc-PC-QDs and sialyl Le(x)-PC-QDs were still retained stably in the whole body after 2 h, while they showed significantly different in vivo dynamics in the tissue distribution, suggesting that structure/sequence of the neighboring sugar residues in the individual sialyl oligosaccharides might influence the final organ-specific distribution. The present results clearly visualize the evidence of an essential role of the terminal sialic acid residue(s) for achieving prolonged in vivo lifetime and biodistribution of various glyco-PC-QDs as a novel class of functional platforms for nanomaterial-based drug targeting/delivery. A standardized protocol using multifunctional PC-QDs should facilitate live animal imaging of ligand-displayed QDs using versatile NIR fluorescence photometry without influence of size-dependent accumulation/excretion pathway for nanoparticles (e.g., viruses) >10 nm in hydrodynamic diameter by the liver.     

Reactions of 2-benzoselenopyrylium salts with hydrazine: a new easy access to 5H-2,3-benzodiazepines

While the solvent-free reactions of the 2-benzoselenopyrylium salts (9) with methyl- or phenylhydrazine afforded the 1-hydrazino-1H-isoselenochromenes (11, 12), the treatment of the salts (9) with anhydrous hydrazine in dry acetonitrile resulted in a ring transformation to give the 5H-2,3-benzodiazepines (13) in one-pot under mild conditions in moderate yields.     

Facilitated Transport of Molecular Oxygen in Membranes of Macromolecular Cobalt-Porphyrin Complex: Modification of Dual-Mode Transport Model

Transport of molecular oxygen is facilitated in poly(butyl methacrylate) membranes containing the cobalt(II)-α,α′,α″,α′″-meso-tetrakis(o-pivalamidophenyl)porphyrin-1-methylimidazole (CoPIm) complex which forms oxygen adduct rapidly and reversibly. The facilitated transport of oxygen is studied by modifying a dual-mode transport model for gas permeation. The diffusion coefficient of oxygen via the fixed CoPIm complexes (Langmuir mode) is assumed to depend on oxygen concentration, and the modified dual-mode transport equation is described for the permeation steady state. The modified equation represents the effect of upstream oxygen pressure on the permeability. The oxygen permeation behavior through the macromolecular-metal complex membrane is discussed.     

Electrical activities of stacking faults and partial dislocations in 4H-SiC homoepitaxial films

The electrical activities of stacking faults (SFs) and partial dislocations in 4H-SiC homoepitaxial films were investigated by using the electron-beam-induced current (EBIC) technique. The basal plane dislocation was dissociated into Si_(g) 30^° and C_(g) 30^° partials under electron-beam irradiation, with a SF formed in between. The SF shows bright contrast at RT and dark contrast at 50 K in EBIC images. The reasons were discussed according to the quantum-well state of SF. C_(g) 30^° partial is always more electrically active than Si_(g) 30^° partial at each specific accelerating voltage. The EBIC contrasts of those two partials were discussed with the number of recombination centers.     

Studies on tellurium-containing heterocycles. Part 20. Reactions of 2-benzoselenopyrylium salts and 2-benzotelluropyrylium salts with nucleophiles: formation of 1-functionalized 1H-isoselenochromenes and 1H-isotellurochromenes

The reactions of the 2-benzoselenopyrylium (1A) and 2-benzotelluropyrylium cations (1B) with a variety of nucleophiles have been investigated. LiAlH(4), sodium alkoxide (NaOMe, NaOi-Pr and NaOt-Bu), diethylamine, n-butylamine and acetone reacted with 1 to give the 1H-isochromenes (2) and the corresponding 1-substituted products (4-9) under mild conditions in almost good to high yields. The 1-alkyl(phenyl)isoselenochromenes (10-13) and 1-benzylisochromenes (18A, 18B), which were produced by the reaction of the salts 1 with Grignard reagents, were converted to the corresponding 1,3-disubstituted 2-benzopyrylium salts (14-17, 19) by treatment with triphenylcarbenium tetrafluoroborate (Ph(3)C(+) BF(4)(-)), respectively. The 1-benzylselenopyrylium salts (19A) and 1-benzyltelluropyrylium salts (19B) exist in the solvent as an equilibrium mixture of the salts (19) and the corresponding (Z)-benzylidene compounds (20).