K. Sueki

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.

RIKEN isotope separator on-line GARIS/IGISOL

Abstract This paper describes the fabrication and the characteristics of an isotope separator on-line (ISOL) which was constructed at the RIKEN Ring Cyclotron Facility. The ISOL consists of a gas-filled recoil separator and an ion-guide isotope separator on-line. Because of this combination the ISOL enables us to study short-lived isotopes of almost all elements.

Activation and tracer techniques for study of metallofullerenes

Advantages and uniqueness of radiochemical techniques in fullerene studies are pointed out. Some experimental data are presented on metallofullerenes production yields, HPLC elution behaviors of Y, La, Gd containing fullerenes, encapsulation of a new metal in the carbon cage, stability of the carbon cage against recoil energy, and the distribution of metallofullerenes among various organs of rats.

New Lanthanoid Metallofullerenes and their HPLC Elution Behavior

Abstract HPLC behaviors of metallofullerenes of 14 lanthanoid elements were studied by use of radiotracers, and the species of some of the metallofullerenes were identified by mass spectroscopy. From the HPLC elution behaviors, 14 lanthanoid elements forming metallofullerenes were found to be grouped into two, namely, Sm, Eu, Tm and Yb as one group and the rest of the elements as another. Some new species of metallofullerenes like La@C74, and M@Cn (M=Eu, Tm, Yb; n=74, 82, 84, 88, 90, 92, 94) have been identified. The observed retention times of metallofullerenes are discussed in terms of the number of carbon atoms of the cage and from consideration of the electron donor and acceptor relation between the fullerene species and the HPLC stationary phases.

New fullerenes of a group IV element: Hf metallofullerenes

Abstract Metallofullerenes of the group IV element Hf have been synthesized in a macroscopic quantity for the first time. The species were purified by HPLC and identified to be Hf 2 C 80 and HfC 84 by TOF/MS measurement. Their HPLC behavior toward the Buckyprep and 5PBB columns were studied systematically in comparison with those of other known fullerene species and HfC 84 is found to have an abnormally large capacity factor for the former column. The UV/VIS/NIR spectrum observed for Hf 2 C 80 and found to include absorption peaks at 406, 511, 567 and 668 nm. No ESR signal could be observed for Hf 2 C 80 .

INS gas-filled recoil isotope separator

Abstract The characteristics and performance of a small sized gas-filled recoil isotope separator recently made at INS are described. The total efficiency and the ΔBρ / Bρ values have been measured using low velocity 16 O, 40 Ar and 68 As ions and found to be 10 and 5%, respectively. The Z -dependence of the mean charge is discussed.

Production and isolation of the isomers of dimetallofullerenes, HoTm@C82 and Tm2@C82

Abstract Metallofullerenes encapsulating Ho and Tm atoms were isolated by using the HPLC method with two different columns. Three isomers of HoTm@C82 and five isomers of Tm2@C82 were identified. The UV–VIS–NIR absorption spectra of these isomer species were similar to those of the corresponding isomers of Er2@C82. This suggests that the cages of HoTm@C82 and Tm2@C82 have the same charge as that of Er2@C82 and that Tm takes the trivalent state in HoTm@C82 and Tm2@C82, contrary to the divalent state in Tm@C82.

FORMATION OF METALLOFULLERENES WITH HIGHER GROUP ELEMENTS

Abstract The formation of metallofullerenes was examined for 23 elements, and some experimental evidence was obtained for metallofullerenes with group-4, Zr and Hf, and group-5, Nb, elements. Relative yields of the metallofullerenes eluted at the retention time around those for M@C 82 (M=group-2 and -3 elements) were found to decrease exponentially as the group number increased. The yields for Fe and Co, namely group-8 and -9 elements, were estimated to be less than one hundredth of that for M@C 82 (M=lanthanoid)

Two deformation paths in proton-induced fission of 232Th☆

Abstract Velocities of complementary fission fragments have been accurately measured by a double velocity time-of-flight method in the proton-induced fission of 232 Th with incident energies from 12.0 to 14.7 MeV. The results experimentally demonstrate for the first time the correlation among the threshold energy, the total fragment kinetic energy, and the mass division mode in fission: one type of the fission process has a lower threshold energy and leads to a compact scission configuration with reflection asymmetry, and the other type has a higher threshold energy and leads to a symmetric elongated scission configuration.

Production and characterization of actinide metallofullerenes

We have, previously, reported on the HPLC elution behavior of the Th, Pa, U, Np, and Am metallofullerenes and the UV/vis/NIR absorption spectra of the Th@C84 and U@C82 species. In this paper, the followings are reported: (1) Pu metallofullerenes were produced and their HPLC elution behavior was investigated using a radiotracer technique. The HPLC chromatogram of this metallofullerene was found to be almost the same as that of the Np and Am metallofullerenes. (2) The oxidation states of Th@C84 and U@C82 produced in macroscopic quantities were examined by XANES (X-ray absorption near edge structure) measurements. The oxidation state of the U atom in the C82 fullerene cage was estimated to be 3+ with the formal charge of the ionic molecule being U3+@C823-.