Effects of hydrated forms of C60 fullerene on amyloid 1-peptide fibrillization in vitro and performance of the cognitive task.

It has been shown for the first time by transmission electron microscopy that the hydrated fullerene C60 inhibited the fibrillization of amyloid-beta25-35 peptide. The fullerene affected the amyloid-beta25-35 assembly, manifesting its anti-amyloidogenic capacity. Our in vivo investigations demonstrated also that a single intracerebroventricular injection of the C60 hydrated fullerene at a dose of 7.2 nmol/ventricle significantly improved the performance of the cognitive task in control rats. The intracerebroventricular injection of the C60 hydrated fullerene (3.6 nmol/ventricle) prevented the impairment of performance of the cognitive task induced by amyloid-beta25-35 (22.5 nmol/ventricle). The results obtained may be useful in the development of therapy of Alzheimer's disease.

Structural features of molecular-colloidal solutions of C60 fullerenes in water by small-angle neutron scattering.

Highly stable and reproducible molecular-colloidal water solutions of C60 fullerenes (FWS) obtained by transferring fullerenes from an organic solution into an aqueous phase with the help of ultrasonic treatment are investigated by means of small-angle neutron scattering (SANS). A polydispersity in the size of detected particles up to 84 nm is revealed. These particles are slightly anisotropic and have a characteristic size of approximately 70 nm. Along with it, there are some indications that a significant part of fullerenes composes particles with the size of the order of 1 nm. The contrast variation based on mixtures of light and heavy water shows that the mean scattering length density of the particles is close to that of the packed fullerene associates as well as that the characteristic size of possible fluctuations of the scattering length density within the particles does not exceed 2 nm. A smooth surface resulting in the Porod law for the scattering is detected. A number of models discussed in the literature are considered with respect to the SANS data.

Protein interaction with hydrated C60 fullerene in aqueous solutions.

Physicochemical effects of hydrated C(60) fullerenes (HyFn) on serum albumin molecules were studied using ESR spin labeling and differential scanning microcalorimetry. Molecular-colloidal solution of hydrated C(60) fullerenes and their small spherical fractal clusters in water (C(60)FWS), was shown to stabilize protein hydration, and decrease specific surface energy in water-protein matrix in salt solutions. The mechanism of HyFn interaction with protein is discussed in terms of HyFn induced formation of protein clusters and phase transition of hydration water.

Direct observation of the alkylation products of deoxyguanosine and DNA by fast atom bombardment mass spectrometry.

By the methods of fast atom bombardment (FAB) mass spectrometry, thin-layer chromatography and ultraviolet absorption spectroscopy adducts have been studied which are formed by an antitumour alkylating drug thiotepa both in a model system, containing only deoxyguanosine (dGuo), and in DNA. Analysis of the model reaction mixture (dGuo + thiotepa) by FAB mass spectrometry permitted observation of adducts dGuo thiotepa, 2dGuo thiotepa, and also the products of their further modification in solution, which occurs by hydrolysis of the glycosidic bond and also by opening of the imidazole ring. In the case of DNA FAB mass spectrometry made it possible to characterize adducts of thiotepa with guanosine (Gua) and adenosine (Ade) without their preliminary purification. The site of alkylation of Gua in both dGuo and DNA is N7, and that of Ade in DNA is N3. The application of the results to the study of the molecular mechanism of the antitumour action of thiotepa is discussed.