Antiamyloid properties of fullerene C<Subscript>60</Subscript> derivatives

A comparative estimation of the ability of complexes of fullerene C₆₀ with polyvinylpyrrolidone and fullerene C₆₀ derivatives (the sodium salt of the polycarboxylic derivative of fullerene C₆₀, sodium fullerenolate), has been carried out. The fullerenes destroyed amyloid fibrils of the Aβ(1–42) peptide of the brain and the muscle X-protein. A study of the effect of fullerenes on muscle actin showed that complexes of fullerene C₆₀ with polyvinylpyrrolidone and sodium fullerenolate did not prevent the filament formation of actin, nor did they destroy its filaments in vitro. Conversely, sodium salt of the polycarboxylic derivative of fullerene C₆₀ destroyed actin filaments and prevented their formation. It was concluded that sodium fullerenolate and complexes of fullerene C₆₀ with polyvinylpyrrolidone are the most effective antiamyloid compounds among the fullerenes examined.     

Fluorescence analysis of the action of soluble derivatives of fullerene C<Subscript>60</Subscript> on amyloid fibrils of the brain peptide Aβ(1–42)

It has been shown by fluorescence analysis in vitro that the water-soluble sodium salt of the polycarboxylic derivative of fullerene C₆₀, fullerenol, and complexes of fullerene C₆₀ with polyvinylpyrrolidone (mol. wt. 25000 and 10000) destroy amyloid fibrils of the brain peptide Aβ(1–42) and prevent their formation. The results of fluorescence analysis confirmed the data obtained earlier by high-resolution electron microscopy. Fluorescence analysis and electron microscopy are complementary methods for the selection of effective antiamyloid drugs.     

Geometrical deformation and failure behavior of C60 fullerene dimer under applied external electric field

By the quantum-molecular dynamics (QMD) technique based on the Roothaan–Hall equation and the Newton motion law, geometrical deformation and failure behavior of C₆₀ fullerene dimer (2C₆₀) as well as single C₆₀ fullerene under applied external electric field are simulated. Further, the effects of the electric field direction on the electric field-induced deformation, polarization-charge distribution and dipole moment of the fullerene molecules are discussed systemically. It is found that the geometrical configuration and failure behavior of the 2C₆₀ molecule are sensitive to the electric field direction, that when the electric field direction is parallel to the bridging C–C bonds of the 2C₆₀ molecule the 2C₆₀ fails easily, and that when the electric field direction is perpendicular to the 2C₆₀ fails difficultly and has the same polarization and failure mechanism as the single C₆₀.     

The effect of C-vacancy on hydrogen storage and characterization of H2 modes on Ti functionalized C60 fullerene A first principles study

Density functional theory calculations were performed to examine the effect of a C vacancy on the physisorption of H₂ onto Ti-functionalized C₆₀ fullerene when H₂ is oriented along the x-, y-, and z-axes of the fullerene. The effect of the C vacancy on the physisorption modes of H₂ was investigated as a function of H₂ binding energy within the energy window (?0.2 to ?0.6 eV) targeted by the Department of Energy (DOE), and as functions of a variety of other physicochemical properties. The results indicate that the preferential orientations of H₂ in the defect-free (i.e., no C vacancy) C₆₀TiH₂ complex are along the x- and y-axes of C₆₀ (with adsorption energies of ?0.23 and ?0.21 eV, respectively), making these orientations the most suitable ones for hydrogen storage, in contrast to the results obtained for defect-containing fullerenes. The defect-containing (i.e., containing a C vacancy) C₅₉TiH₂ complex do not exhibit adsorption energies within the targeted energy range. Charge transfer occurs from Ti 3d to C 2p of the fullerene. The binding of H₂ is dominated by the pairwise support–metal interaction energy E(i)^Cn...Ti, and the role of the fullerene is not restricted to supporting the metal. The C vacancy enhances the adsorption energy of Ti, in contrast to that of H₂. A significant reduction in the energy gap of the pristine C₆₀ fullerene is observed when TiH₂ is adsorbed by it. While the C _n fullerene readily participates in nucleophilic processes, the adjacent TiH₂ fragment is available for electrophilic processes.

Effect of fullerenes C<Subscript>60</Subscript> on X-protein amyloids

The inhibitory effect of hydrated fullerene C₆₀ and the sodium salt of the fullerene polycarboxylic derivative C₆₀Cl(C₆H₄CH₂COONa)₅ on the formation of amyloid fibrils by X-protein in vitro has been studied by electron microscopy. It is shown that these compounds not only destroy mature amyloid fibrils but also prevent the formation of new fibrils. This property of fullerenes, which are nanoparticles, can be used to develop a novel medical nanotechnology in the therapy for amyloidoses.     

Fullerene Nucleating Agents: A Route Towards Thermally Stable Photovoltaic Blends

The bulk‐heterojunction nanostructure of non‐crystalline polymer:fullerene blends has the tendency to rapidly coarsen when heated above its glass transition temperature, which represents an important degradation mechanism. We demonstrate that fullerene nucleating agents can be used to thermally arrest the nanostructure of photovoltaic blends that comprise a non‐crystalline thiophene‐quinoxaline copolymer and the widely used fullerene derivative [6,6]‐phenyl‐C₆₁‐butyric acid methyl ester (PCBM). To this end, C₆₀ fullerene is employed to efficiently nucleate PCBM crystallization. Sub‐micrometer‐sized fullerene crystals are formed when as little as 2 wt% C₆₀ with respect to PCBM is added to the blend. These reach an average size of only 200 nanometers upon introduction of more than 8 wt% C₆₀. Solar cells based on C₆₀‐nucleated blends indicate significantly improved thermal stability of the bulk‐heterojunction nanostructure even after annealing at an elevated temperature of 130 °C, which lies above the glass transition temperature of the blend. Moreover, we find that various other compounds, including C₇₀ fullerene, single‐walled carbon nanotubes, and sodium benzoate, as well as a number of commercial nucleating agents—commonly used to clarify isotactic polypropylene—permit to control crystallization of the fullerene phase.     

Syntheses of water-soluble [60]fullerene derivatives and their enhancing effect on neurite outgrowth in NGF-treated PC12 cells

Water-soluble [60]fullerene (C₆₀) derivatives were synthesized to examine their bioactivities. PC12 cells were used as a model of nerve cells and the bioactivities of synthesized C₆₀ derivatives together with some reported ones were tested. Among the compounds tested, C₆₀/(γ-CyD)₂, C₆₀-bis(γ-CyD) (5) containing C₆₀-mono(γ-CyD) (5′), and C₆₀/PVP were sufficiently soluble in water and showed an enhancing effect on the neurite outgrowth of NGF-treated PC12 cells.     

Tissue Sites of Uptake ofC-Labeled C60

This paper describes thein vivobehavior and potential metabolism of C₆₀and a more water-soluble quaternary ammonium salt-derivatized C₆₀. In both cases, a¹⁴C-labeled fullerene core was utilized for the target molecules that were intravenously injected into female Sprague–Dawley rats. The¹⁴C-labeled C₆₀(*C₆₀) was rapidly (within 1 min) cleared from the circulation and the majority of the *C₆₀accumulated in the liver (90–95%). *C₆₀was not eliminated from the liver over the 120-h period of this study. Our results also suggest that C₆₀is not metabolized by the typical oxidative patterns characteristic of other polycyclic aromatics. Therefore, although not acutely toxic, use of C₆₀, or its derivatives that could be cleaved back to the parent C₆₀in vivo, would likely lead to long-term fullerene accumulation in the liver. The uptake of *C₆₀and¹⁴C-labeled ammonium salt-derivatized C₆₀(1)by human keratinocytesin vitroshowed that while both *C₆₀and1are readily taken up by cells,1accumulates more slowly. Additionally, while C₆₀, at rather high concentrations (2.0 μM) and over extended periods of time (8 days), is able to inhibit the growth of human keratinocytes by about 50%, this effect showed little, if any, photoinducability.     

Co-Exposure with Fullerene May Strengthen Health Effects of Organic Industrial Chemicals

In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C₆₀ fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C₆₀ and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C₆₀ and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C₆₀ that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C₆₀ that is slightly less cytotoxic than m-cresol. Hydrophobicity of chemicals correlates with co-effects when secretion of pro-inflammatory cytokines IL-1β and TNF-α is considered. Complementary atomistic molecular dynamics simulations reveal that C₆₀ co-aggregates with all chemicals in aqueous environment. Stable aggregates have a fullerene-rich core and a chemical-rich surface layer, and while essentially all C₆₀ molecules aggregate together, a portion of organic molecules remains in water.     

Effect of nitroderivatives of fullerene C<Subscript>60</Subscript> on amyloid fibrils of the brain Aβ(1–42) peptide and muscle X-protein

The antiamyloidogenic capacity of water-soluble nitroderivatives of fullerene C₆₀: methyl ester of L-N-[(2-nitroglyceryl) fullerenyl] proline, methyl ester of L-N-[(2,3-dinitroglyceryl) fullerenyl] proline, and 2-nitroxyethyl ester of L-N-([2-(nitroxy) ethyl] fullerenyl) proline has been studied in vitro by high-resolution electron microscopy. It was shown that these fullerene C₆₀ nitroderivatives are able to prevent the formation of amyloid fibrils by the brain Aβ(1–42)-peptide and muscle X-protein and to destroy mature fibrils. Electron microscopy is a promising method for selecting effective antiamyloidogenic drugs. The antiamyloidogenic activity of nanodimensional fullerene C₆₀ nitroderivatives offers strong possibilities for creating a new nanotechnology for the therapy of amyloidoses.     

Study of Mutagenic Activity of Fullerene and Some of Its Derivatives Using His+ Reversions of Salmonella typhimurium as an Example

The influence of three new derivatives of fullerene C₆₀ ([61]dimethoxyphosphoryl[61]carbethoxy-methano[60]fullerene, [61](dimethoxyphosphoryl[61]carbmethoxy-methanofullerene, and 1-methyl-2-(3,5-ditretbutyl-4-hydroxy-phenyl),3,4-fulleropyrrolidine) on the appearance of His+ reversions in the Salmonella typhimurium strain BA13 was studied. It was ascertained that the effect of fullerene derivatives on the occurrence of mutations depends on the type of the molecular group with which fullerene interacts. The biological effect is determined not only by the action of the group associated with fullerene. The dependence between the mutagenic effect and properties of the solvents was detected. Exposure to visible light of the culture treated with fullerene derivatives was found to have an antimutagenic effect in the case of [61]dimethoxyphosphoryl[61]carbethoxy-methanofullerene[60]. For two other derivatives, the differences between experimental and control variants were statistically nonsignificant.     

Enhanced brain penetration of hexamethonium in complexes with derivatives of fullerene C<Subscript>60</Subscript>

The present report describes development of hexamethonium complexes based on fullerene C₆₀. Hexamethonium has a limited penetration into CNS and therefore can antagonize central effects of nicotine only when given at high doses. In the present studies conducted in laboratory rodents, intraperitoneal administration of hexamethonium-fullerene complexes blocked effects of nicotine (convulsions and locomotor stimulation). When compared to equimolar doses of hexamethonium, complexes of hexamethonium with derivatives of fullerene C₆₀ were 40 times more potent indicating an enhanced ability to interact with central nicotine receptors. Thus, fullerene C₆₀ derivatives should be explored further as potential carrier systems for polar drug delivery into CNS.     

Adsorption of Cu(II) on Oxidized Multi-Walled Carbon Nanotubes in the Presence of Hydroxylated and Carboxylated Fullerenes

The adsorption of Cu(II) on oxidized multi-walled carbon nanotubes (oMWCNTs) as a function of contact time, pH, ionic strength, temperature, and hydroxylated fullerene (C₆₀(OH)_n) and carboxylated fullerene (C₆₀(C(COOH)₂)_n) were studied under ambient conditions using batch techniques. The results showed that the adsorption of Cu(II) had rapidly reached equilibrium and the kinetic process was well described by a pseudo-second-order rate model. Cu(II) adsorption on oMWCNTs was dependent on pH but independent of ionic strength. Compared with the Freundlich model, the Langmuir model was more suitable for analyzing the adsorption isotherms. The thermodynamic parameters calculated from temperature-dependent adsorption isotherms suggested that Cu(II) adsorption on oMWCNTs was spontaneous and endothermic. The effect of C₆₀(OH)_n on Cu(II) adsorption of oMWCNTs was not significant at low C₆₀(OH)_n concentration, whereas a negative effect was observed at higher concentration. The adsorption of Cu(II) on oMWCNTs was enhanced with increasing pH values at pH < 5, but decreased at pH ≥ 5. The presence of C₆₀(C(COOH)₂)_n inhibited the adsorption of Cu(II) onto oMWCNTs at pH 4–6. The double sorption site model was applied to simulate the adsorption isotherms of Cu(II) in the presence of C₆₀(OH)_n and fitted the experimental data well.     

Computational study of enantioselective interaction between C<Subscript>60</Subscript> fullerene and its derivatives with L-histidine

The mechanism of the enantioselective binding of L-histidine with C₆₀ fullerene and its derivatives, (1,2-methanofullerene C₆₀)-61-carboxylic acid, diethyl (1,2-methanofullerene C₆₀)-61-61-dicarboxylate and tert-butyl (1,2-methanofullerene C₆₀)-61-carboxylate based chiral selectors was studied by quantum chemical calculations. All the molecules were fully optimized at RHF/6-31G* basis set. Relative energies between the different complexes were subsequently estimated with single-point electronic energies computed using Møller-Plesset perturbation theory (MP2). Stability and feasibility of all the generated structures were supported by their respective energy minima and fundamental frequencies. It was observed that interaction of fullerene derivatives with L-histidine is due to the existence of hydrogen bonding forces during the complex formation. The intermolecular forces, flow of atomic charges, binding energy, hardness, dipole moment and localization of electrostatic potential are in agreement with enantioselective interaction of L-histidine with C₆₀ fullerene and its derivatives. It is found that theoretical evaluation to be consistent with the experimental data.     

Quantitative analysis of C60 fullerene in blood and tissues by high-performance liquid chromatography with photodiode-array and mass spectrometric detection

A high-performance liquid chromatographic (HPLC) assay method for C₆₀ fullerene, in blood, liver and spleen using photodiode-array detection or mass spectrometric detection (LC–MS) and C₇₀ fullerene, as the internal standard, is described. The recovery from mouse blood and tissues spiked with micronized C₆₀ exceeds 90%. The method is linear from 0.05 to 200 mg of C₆₀ per liter of blood and from 0.05 to 5.00% of C₆₀ per tissue weight. The limit of detection of the method is 0.1 ng of C₆₀ per injection. This method was applied to mouse blood and tissue samples after intraperitoneal administration of a micronized C₆₀ suspension.     

Permeation of skin with (C60) fullerene dispersions

Dispersions in transcutol/isopropyl myristate make C₆₀ fullerene molecules suitable for transdermal delivery. We found that C₆₀ can successfully permeate the skin using pig skin in Franz diffusion cells. Molecular dynamics simulations and transmission electron microscopy confirmed these observations. Basic cosmetic formulations with transcutol/isopropyl myristate without harsh organic solvents show a high potential for delivery of C₆₀ for biopharmaceutical and cosmetics applications.     

Toxic effect of Aβ<Subscript>25–35</Subscript> and fullerene C<Subscript>60</Subscript> on erythrocytes

Using light microscopy and spectrophotometry, it has been shown that amyloid β-peptide Aβ_25–35 and water-soluble fullerene C₆₀ cause lysis of human and rat erythrocytes. Both fullerene C₆₀ and Aβ_25–35 partly inhibited the activities of membrane-associated phosphofructokinase and cytoplasmic lactate dehydrogenase in erythrocytes.     

Fully exohydrogenated Si60 fullerene cage

Using first-principles calculations based on density functional theory, we demonstrate that Si₆₀ fullerene cage can be stabilized by exohydrogenated method. In contrast to previous theoretical studies that Si₆₀ fullerene geometry construction will be seriously distorted when it is bare or encapsulated by metal atom clusters, exohydrogenated scheme shows that Si₆₀H₆₀ cage will be able to keep perfect fullerene structure similar to C₆₀.     

C<Subscript>60</Subscript> fullerene affects elastic properties and osmoregulation reactions of human lymphocytes

The influence of aqueous solution of pristine C₆₀ fullerene (C₆₀FAS) on functional activity of lymphocytes from a healthy person was studied for the first time. By means of atomic force microscopy, it was found that C₆₀FAS in a concentration of 0.1 mg/ml increases the stiffness of the lymphocyte membrane by 41 % (p < 0.05) and lowers the functional activity of the plasmalemma surface, thereby constraining the use of its membrane material in physiological reactions using a hypotonic model in vitro. However, a cell retains the ability to regulate its volume and demonstrates relative resistance to hypo-osmotic stress. The resistance of lymphocytes in hypo-osmotic medium is facilitated by activation of the nucleus by C₆₀ fullerene particles, which regulates the implementation of two consistent phases of an increase and decrease of cell volume, thereby retaining cell viability. All these indicate the impact of C₆₀ fullerene on the cellular nucleus.     

Fullerene nanoparticles for the treatment of ulcerative colitis

Ulcerative colitis (UC) is a long-term, recurrent inflammatory bowel disease for which no effective cure is yet available in the clinical setting. Repairing the barrier dysfunction of the colon and reducing intestinal inflammation are considered key objectives to cure UC. Here we demonstrate a novel therapeutic strategy based on a C₆₀ fullerene suspension (C₆₀FS) to treat dinitrobenzene sulfonic acid-induced UC in an animal model. C₆₀FS can repair the barrier dysfunction of UC and effectively promote the healing of ulcers; it also manifests better treatment effects compared with mesalazine enema. C₆₀FS can reduce the numbers of basophils in the blood of UC rats and mast cells in the colorectal tissue, thereby effectively alleviating inflammation. The expression of H1R, H4R, and VEGFR2 receptors in colorectal tissues is inhibited by C₆₀FS, and the levels of histamine and prostaglandin in the rat blood are reduced. This work presents a reliable strategy based on fullerene to cure UC and provides a novel guide for UC treatment.