RESUMEN
The use of gold nanoparticles as imaging agents and therapeutic delivery systems is growing rapidly. However, a significant limitation of gold nanoparticles currently is their low absorption efficiencies in the gastrointestinal (GI) tract following oral administration. In an attempt to identify ligands that facilitate gold nanoparticle absorption in the GI tract, we have studied the oral bioavailability of 2.0 nm diameter gold nanoparticles modified with the small molecules p-mercaptobenzoic acid and glutathione, and polyethylene glycols (PEG) of different lengths and charge (neutral and anionic). We show that GI absorption of gold nanoparticles modified with the small molecules tested was undetectable. However, the absorption of PEGs depended upon PEG length, with the shortest PEG studied yielding gold nanoparticle absorptions that are orders-of-magnitude larger than observed previously. As the oral route is the most convenient one for administering drugs and diagnostic reagents, these results suggest that short-chain PEGs may be useful in the design of gold nanoparticles for the diagnosis and treatment of disease.
Asunto(s)
Tracto Gastrointestinal/metabolismo , Oro/química , Oro/farmacocinética , Nanopartículas del Metal , Tamaño de la Partícula , Animales , Disponibilidad Biológica , Femenino , Glutatión/química , Mercuribenzoatos/química , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Conformación Molecular , Polietilenglicoles/químicaRESUMEN
An efficient method for the selective "N1" alkylation of indazoles is described. Use of alpha-halo esters, lactones, ketones, amides, and bromoacetonitrile provides good to excellent yield of the desired N1 products.
Asunto(s)
Técnicas Químicas Combinatorias , Indazoles/síntesis química , Alquilación , Catálisis , Indazoles/química , Estructura MolecularRESUMEN
The total synthesis of (+)-dihydrocompactin via an intramolecular ionic Diels-Alder reaction that proceeds with remote stereocontrol is described. This reaction proceeds by an intermediate vinyl-oxocarbenium ion (6), the conformational constraints of which lead to the observed asymmetric induction. The sense of asymmetric induction appears contrasteric and is explained by the proposed reactive conformation shown in Figure 1.