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Three-component coupling reaction of (pent-3-oxy)acetaldehyde, ( Z )- N -(2-nitrovinyl)acetamide, and tetraethyl 1,1-diylbis(phosphonate) is performed in a one-pot operation, followed by reduction of the nitro group and hydrolysis of the phosphonate ester, to afford 8.7% overall yield of tamiphosphor as a potent neuraminidase inhibitor with IC 50 and EC 50 values of 2.5 and 31.5 nM against wild-type H1N1 influenza virus. The tamiphosphor (5 R )-epimer is a less active anti-influenza agent with IC 50 and EC 50 values of 39 and 117 nM.

One of the pathologic hallmarks in Alzheimer's disease (AD) is extracellular senile plaques composed of amyloid-β (Aβ) fibrils. Blocking Aβ self-assembly or disassembling Aβ aggregates by small molecules would be potential therapeutic strategies to treat AD. In this study, we synthesized a series of rationally designed divalent compounds and examined their effects on Aβ fibrillization. A divalent amide (2) derived from two molecules of caffeic acid with a propylenediamine linker of ∼5.0 A in length, which is close to the distance of adjacent β sheets in Aβ fibrils, showed good potency to inhibit Aβ(1–42) fibrillization. Furthermore, compound 2 effectively dissociated the Aβ(1–42) preformed fibrils. The cytotoxicity induced by Aβ(1–42) aggregates in human neuroblastoma was reduced in the presence of 2, and feeding 2 to Aβ transgenic C. elegans rescued the paralysis phenotype. In addition, the binding and stoichiometry of 2 to Aβ(1–40) were demonstrated by using electrospray ionization−traveling wave ion mobility−mass spectrometry, while molecular dynamic simulation was conducted to gain structural insights into the Aβ(1–40)−2 complex.

We have successfully introduced biological gelatin particles as center cores acting as shape and structure directors to form superparamagnetic hollow and paramagnetic porous Gd2O3 particles, which have average sizes below 200 nm. Two approaches involving sol−gel processes and precursor deposition induced by solvent evaporation were employed to fabricate hollow and porous particles, respectively. The magnetization measurements including ZFC-FC curves and magnetization vs H/T as well as their usefulness for in vitro MR imaging were investigated for Gd2O3 particles. With the presence of carbon residue on the hollow Gd2O3 surface, the hollow Gd2O3 particles exhibited superparamagnetic behavior. However, these hollow species turned paramagnetic after removal of the carbon-based residue. The hollow and porous Gd2O3 nanospheres all indicated satisfactory biocompatibility from the measurements of the leaching behavior of Gd3+ ions and cell culture viability. We found, from positive contrast images in in vitro MR ...

The solution approach was employed to yield multifunctional amorphous Gd 2 O(CO 3 ) 2 . H 2 O colloidal spheres by reflux of an aqueous solution containing GdCl 3 .6H 2 O and urea. By elongating the reaction time, crystalline rhombus-shaped Gd 2 O(CO 3 ) 2 . H 2 O with at least 87% yield could be formed and were also accompanied by some rectangular particles. High-resolution synchrotron powder X-ray diffraction provides crystal structure information, such as cell dimensions, and indexes the exact crystal packing with hexagonal symmetry, which is absent from the Joint Committee on Powder Diffraction Standards file, for the crystalline rhombus sample. Particle formation was studied based on the reaction time and the concentration ratio of [urea]/ [GdCl 3 · 6H 2 O]. After a calcination process, the amorphous spheres and crystalline rhombus Gd 2 O(CO 3 ) 2 · H 2 O particles convert into crystalline Gd 2 O 3 at temperatures above 600 °C. For in vitro magnetic resonance imaging (MRI), both Gd 2 O(CO 3 ) 2 · H 2 O and Gd 2 O 3 species show the promising T 1 - and T 2 -weighted effects and could potentially serve as bimodal T 1 -positive and T 2 -negative contrast agents. The amorphous Gd 2 O(CO 3 ) 2 · H 2 O contrast agent further demonstrates enhanced contrast of the liver and kidney using a dynamic contrast-enhanced MR imaging (DCE-MRI) technique for in vivo investigation. The multifunctional capability of the amorphous Gd 2 O(CO 3 ) 2 · H 2 O spheres was also evidenced by the formation of nanoshells using these amorphous spheres as the template. Surface engineering of the amorphous Gd 2 O(CO 3 ) 2 · H 2 O spheres could be performed by covalent bonding to form hollow silica nanoshells and hollow silica@Fe 3 O 4 hybrid particles.

Of the methods employed in the preparation of one-dimensional lanthanide phosphate (LnPO(4)) nanorods/nanowires, such as GdPO(4), the hydrothermal method has been mainly used as a synthetic route. In this study, we report a facile low-temperature solution approach to prepare GdPO 4*H(2)O nanorods by simply refluxing GdCl(3) and KH(2)PO(4) for only 15 min at 88 degrees C, an approach that can easily be scaled up by increasing the reagent amounts. We observed a highly viscous macroscopic hydrogel-like material when we mixed as-prepared GdPO(4)*H(2)O nanomaterials with H(2)O. Hydrogels are an important class of biomaterials. Their building blocks, normally formed from protein-, peptide-, polymer-, and lipid-based materials, offer three-dimensional scaffolds for drug delivery, tissue engineering, and biosensors. Our preliminary results showed that GdPO(4)*H(2)O hydrogels could be used for encapsulation and drug release, and that they were biocompatible, acting as scaffolds to foster cell proliferation. These findings suggested that they might have biomedical uses. Our findings may lead to the creation of other inorganic nanomaterial-based hydrogels apart from the organic and biomolecular protein-, peptide-, polymer-, and lipid-based building blocks.

Nanocontrast agents have great potential in magnetic resonance (MR) molecular imaging applications for clinical diagnosis. We synthesized Au 3 Cu 1 (gold and copper) nanoshells that showed a promising MR contrast effect. For in vitro MR images, the large proton r 1 relaxivities brightened T 1 -weighted images. As for the proton-dephasing effect in T 2 , Au 3 Cu 1 lightened MR images at the low concentration of 0.125 mg mL -1 (3.84 x 10 -7 mM), and then the signal continuously decreased as the concentration increased. For in vivo MR imaging, Au 3 Cu 1 nanocontrast agents enhanced the contrast of blood vessels and suggested their potential use in MR angiography as blood-pool agents. We propose that (1) the cooperativity originating from the form of the nanoparticles and (2) the large surface area coordinated to water from their porous hollow morphology are important for efficient relaxivity. In a cytotoxicity and animal survival assay, Au 3 Cu 1 nanocontrast agents showed a dose-dependent toxic effect: the viability rate of experimental mice reached 83% at a dose of 20 mg kg -1 and as much as 100% at 2 mg kg -1 .

A low-temperature solution approach (90-95 degrees C) using FeCl(3) and urea was carried out to synthesize beta-FeOOH nanorods in aqueous solution. The as-synthesized beta-FeOOH nanorods were further calcined at 300 degrees C to form porous nanorods with compositions including both beta-FeOOH and alpha-Fe(2)O(3). The derived porous nanorods were engineered to assemble with four layers of polyelectrolytes (polyacrylic acid (PAA)/polyethylenimine(PEI)/PAA/PEI) on their surfaces as polyelectrolyte multilayer nanocapsules. Fluorescein isothiocyanate (FITC) molecules were loaded into the polyelectrolyte multilayer nanocapsules in order to investigate drug release and intracellular delivery in Hela cells. The as-prepared nanocapsules showed ionic strength-dependent control of the permeability of the polyelectrolyte shells. The release behavior of the entrapped FITC from the FITC-loaded nanocapsules exhibited either controlled- or sustained-release trends, depending on the compactness of the polyelectrolyte shells on the nanorod surfaces. Cytotoxicity measurements demonstrate that the native nanorods and the polymer-coated nanorods have excellent biocompatibility in all dosages between 0.1 ng mL(-1) and 100 microgm L(-1). The time dependence of uptake of FITC-loaded nanocapsules by Hela cancer cells observed by laser confocal microscopy indicates that the nanocapsules can readily be taken up by cancer cells in 15 min, a relatively short period of time, while the slow release of the FITC from the initial perimembrane space into the cytoplasm was followed by release into the nucleus after 24 h.