In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity.

BACKGROUND: Water-soluble fullerenes have recently been shown to exhibit considerable in vitro biological activity including cytotoxicity, site-selective DNA cleavage and inhibition of HIV protease. To assess the potential of these compounds as drugs, studies on the in vivo behavior of fullerenes are needed. We therefore set out to synthesize a radiolabeled, water-soluble fullerene, in order to obtain data on the oral absorption, distribution and excretion of this class of compounds. RESULTS: We synthesized a 14C-labeled water-soluble [60]fullerene using dipolar trimethylenemethane, which undergoes cycloaddition to [60]fullerene. When administered orally to rats, this compound was not efficiently absorbed and was excreted primarily in the feces. When injected intravenously, however, it was distributed rapidly to various tissues, and most of the material was retained in the body after one week. The compound was also able to penetrate the blood-brain barrier. Acute toxicity of the water-miscible fullerene was found to be quite low. CONCLUSIONS: Although the water-soluble fullerenes (and possibly their simple metabolites) are not acutely toxic, they are retained in the body for long periods, raising concerns about chronic toxic effects. The fact that fullerenes distribute rapidly to many tissues suggests that they may eventually be useful to deliver highly polar drugs through membranes to a target tissue, however, and they may even have applications in the delivery of drugs to the brain. Recent advances in fullerene synthetic chemistry may also make it possible to control fullerene absorption/excretion profiles in the future.

A new, iterative strategy of oligosaccharide synthesis based on highly reactive beta-bromoglycosides derived from selenoglycosides.

Stereoselective conversion of a selenoglycoside to a beta-bromoglycoside in the absence of a glycosyl acceptor followed by the coupling with another selenoglycoside affords the corresponding glycosylated selenoglycoside, which could be directly used for the next glycosylation. The iteration of this sequence allows the synthesis of a variety of oligosaccharides including an elicitor active heptasaccharide. [reaction: see text]

Synthetic and theoretical studies on group-transfer imidoylation of organotellurium compounds. remarkable reactivity of isonitriles in comparison with carbon monoxide in radical-mediated reactions.

Imidoylation of organotellurium compounds with isonitriles has been investigated in conjunction with the radical-mediated C1 homologation reaction by using CO and isonitriles. Carbon-centered radicals generated photochemically or thermally from organotellurium compounds react with isonitriles in a group-transfer manner to give the corresponding imidoylated products. Organotellurium compounds have been found to serve as effective precursors of a wide variety of stabilized radicals, namely benzyl, alpha-alkoxy, alpha-amino, and acyl radicals, which take part in the imidoylation with high efficiency. The reactions are compatible with various functional groups, and can be carried out in various solvents including environmentally benign water. The reactivity of isonitriles has been compared with that of CO through competition experiments, and the results indicate that isonitriles are superior to CO as radical acceptors in reactions with stabilized radicals. The origin of the differences has been addressed in theoretical studies with density functional theory calculations using the B3LYP hybrid functional. The calculations suggest that both carbonylation and imidoylation proceed with low activation energies, and that there are virtually no differences in the kinetic sense. Instead, it indicates that thermodynamic effects, namely differences in the stability of the acyl and the imidoyl radicals, control the overall course of the reactions.

Photocytotoxicity of water-soluble fullerene derivatives.

New water-soluble fullerene carboxylic acids (1 and 2) derived from C60 and C70 fullerenes, respectively, were examined for photocytotoxicity toward Raji cells (B lymphocyte). These compounds did not show any photocytotoxic effect even at 50 microM, while pheophorbide a showed significant photocytotoxicity at 0.5 microM. Therefore, fullerene derivatives derived from C60 and C70 would not be practical agents for photodynamic therapy.

Highly efficient and chemoselective reductive bis-silylation of quinones by silyltellurides

Silyltellurides serve as new silicon-based chemoselective reducing agents and reduce quinones to the corresponding bis-silylated hydroquinones. The reaction proceeds under ambient thermal conditions without the need of any additional promoters or catalysts and gives the products in excellent yields. Several control experiments suggest that the reaction is initiated by a single electron transfer from silyltellurides to quinones.