Preparation and characterization of self-assembled nanoparticles based on glycol chitosan bearing adriamycin

An anthracycline drug, adriamycin, was chemically conjugated onto the backbone of glycol chitosan via an acid-labile cis-aconityl linkage. The physicochemical characteristics of the glycol chitosan–adriamycin (GC–ADR) conjugates were investigated by dynamic light scattering, atomic force microscopy, and fluorescence spectroscopy. The GC–ADR conjugates were capable of forming nano-sized self-aggregates in an aqueous medium, when the adriamycin content in the conjugate was in the range of 2.0–5.0 wt.%. The self-aggregates were spherical in shape, and had mean diameters of 238–304 nm, depending on the adriamycin content. The critical aggregation concentrations of the conjugates, estimated by the fluorescence quenching method, were as low as 1.0–2.5×10⁻² mg/ml. The size of self-aggregates was not affected by the polymer concentration in the range from 50 to 2,000 μg/ml, and was maintained up to 8 days in phosphate-buffered saline (pH 7.4), indicating high colloidal stability. The release of adriamycin from self-aggregates was significantly dependent on the pH of the medium due to the cis-aconityl linkage; e.g., the amount of adriamycin released for 4 days was 7.3±0.3% at pH 7, whereas it was 29.3±1.9% at pH 4. The cell viability results demonstrated that free adriamycin shows more potent cytotoxicity than the conjugates, primarily attributed to the sustained release of adriamycin from self-aggregates. In conclusion, the self-aggregates, formed by GC–ADR conjugates, might be useful for the site-specific delivery of adriamycin in a sustained manner.     

Mono-layer of Ni(100-x)Fe(x) nanoparticles fabricated on a polyimide film under different curing atmospheres

A mono-layer of nano-sized metal particles was prepared on the surface of a polyimide film by simply depositing a thin film of Ni80Fe20 on top of the polyamic acid that was spin coated onto a Si wafer. During thermal imidization of the polyamic acid film, Fe was selectively etched by reacting with the carbonyl group of the polyamic acid to leave behind uniformly distributed Ni-rich metallic particles. The average diameter of the particles was 4 nm and the particles were confined into a single layer on top of the polymer film. Moreover, it was also shown that the morphology of the nanoparticles can be substantially altered by curing the precursor film in a hydrogen atmosphere, without significantly damaging the polymer film. Thus produced nanoparticles lay exposed on top of the electrically insulating and chemically stable polymer film so that it is possible that the nanoparticles can be directly used for fabricating a nonvolatile flash memory device or as a template for building functional nano-structures.     

Ring opening versus ring expansion in rearrangement of bicyclic cyclobutylcarbinyl radicals

Ring opening and expansion of multicyclic cyclobutylcarbinyl radicals provides an appealing method for the construction of heavily substituted ring systems in a stereocontrollable fashion. Here we conducted the first, systematic study on the regioselectivity in the rearrangement of various synthetically relevant cyclobutylcarbinyl radicals. It was found that a two-layer ONIOM method, namely ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(2df,2p)), could accurately predict the free energy barriers of the ring openings of cyclobutylcarbinyl radicals with a precision of 0.3 kcal/mol. By using this powerful tool we found that the regiochemistry for the ring opening of monocyclic cyclobutylcarbinyl radicals could be easily predicted by the relative stability of the two possible carbon radical products. A linear correlation was found between the activation and reaction free energies. This observation indicated that the ring opening of cyclobutylcarbinyl radicals was strongly affected by the thermodynamic factors. On the basis of the above results we extended our study to the rearrangement of bicyclic cyclobutylcarbinyl radicals that could undergo both ring opening and expansion. It was found that for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the bridge methyl group, ring expansion was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring adjacent to the bridge methyl group. On the other hand, for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the 2-position, ring opening was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring at the bridge position.