A. I. Kotel’nikov

Study of the neuroprotective action of hybrid structures based on fullerene C60

The neuroprotective action of hybrid structures based on fullerene C60 with attached proline amino acid has been studied. Hybrid structures contained natural antioxidant carnosine or addends with one or two nitrate groups. It has been shown that all studied compounds had antioxidant activity and decreased the concentration of malondialdehyde in homogenates of the rat brain. Compound I, which contained the antioxidant carnosine, has been found to be the most effective antioxidant. All compounds except IV and V inhibited the activity of monoamine oxidase B, while compounds I–IV increased the activity of monoamine oxidase A. All investigated compounds inhibited glutamate-induced Ca2+ uptake into synaptosomes of the rat brain cortex. Compound III, containing two nitrate groups, has been found to be the most effective inhibitor. This compound caused a significant increase of the currents of AMPA receptors (AMPA, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid).

Photodynamic activity of a hybrid nanostructure based on a polycationic fullerene derivative and phthalocyanine dye photosens

229 As known, fullerenes are photoexcited to a triplet state in 100% quantum yield, which then is deacti vated to generate, depending on the polarity of a medium, either singlet oxygen О2 or superoxide radi cal anions and other active radicals [1]. Numerous studies have addressed the photodynamic effect of fullerene and their derivatives: the generation of active radicals upon photoexcitation is responsible for dam age of DNA, proteins, and membranes, as well as for the suppression of the reproduction of tumor cells, viruses, and bacteria [2]. However, the efficiency of the photodynamic action of fullerenes and the pros pects for their application in medicine are essentially limited by the weak absorption by fullerenes of visible light, especially in the range 650–800 nm, which is most suitable for photodynamic therapy. The photodynamic effect of fullerenes can be con siderably enhanced by creating hybrid nanostructures − О2 . (HNSs) via the formation of a fullerene complex with a dye that efficiently absorbs visible light [3]. In such a complex, the dye can efficiently absorb light and transfer excitation energy or electron to the fullerene. Further excitation transfer or electron transfer from the fullerene to molecular oxygen will generate active oxygen species. The creation of such an HNS based on fullerene and a dye can thereby significantly enhance the efficiency of photodynamic therapy.

Estimation of membrane activity of water-soluble polysubstituted fullerene derivatives by luminescence methods

Patterns of the interaction between water-soluble polysubstituted fullerene derivatives (PFDs) and the lipid bilayer of phosphatidylcholine liposomes were investigated by applying triplet and fluorescent probes. Objective quantitative criteria have been proposed for the evaluation of membranotropic action of chemical substances, notably, fullerene derivatives that quench fluorescent probes with different localizations within the membrane. Thus, the defined criteria are the rate constants for the quenching of the fluorescence of triplet probes and the equilibrium constants for PFD-probe complexes, which characterize their stability. The localization of PFDs in the membrane was determined by comparing rate constants for the quenching of eosin phosphorescence and equilibrium constants for PFD-chromophore complexes. In addition, the efficiency of the interaction of PFDs with various sites of the phospholipid membrane has been seen to depend on the charge of addends that are attached to the polysubstituted derivatives.

Analysis of microsecond relaxation dynamics of proteins and viscous media by recording relaxation shifts of phosphorescence spectra

We studied the low-temperature dynamics of the Stokes shift of instantaneous phosphorescence spectra of eosin and eosin maleimide covalently bound to hemoglobin in a 66% v/v aqueous solution of glycerol under conditions of pulsed excitation. The kinetics of the Stokes shifts are described using the Cole-Davidson distribution function. From the experimental data, we obtain the parameters τ0 and β, which describe the Cole-Davidson distribution. Values of τ0 and β agree well with data obtained by other methods, and these parameters can be used to describe electron transfer reactions in polar solutions and proteins.

Properties of Low-Temperature Spectral Relaxation of Eosin Phosphorescence in a Glycerol-Water Mixture

The low-temperature dynamics of the Stokes shift of the instantaneous phosphorescence spectra of eosin in 94% glycerol-water solution is studied upon pulsed excitation. At temperatures T<Ttg, where Tg=183–187 K is the glass transition temperature of the solution, the blue shift of the instantaneous phosphorescence spectra is observed. In the vicinity of Tg, the spectral dynamics undergoes inversion, and the red shift of the instantaneous spectra is observed at temperatures between 188 and 210 K, which is caused by freezing out the orientation mobility of the solvent molecules in the first solvate shells of the chromophore molecule. In the temperature range from 230 to 273 K, the enhancement effect was observed at the initial parts of phosphorescence kinetic curves, which is probably explained by cooperative phenomena in the solvent.

Design of a hybrid nanostructure based on fullerene C60 and biologically active substance for modeling physiological properties of compounds

The effects of cognitive-stimulating substance BD-2 of the γ-carboline family and a hybrid compound based on fullerene C60 and attached BD-2 on various aspects of the behavior of animals were studied. The synthesized hybrid fullerene compound (HFC) has no side psychostimulating effect characteristic of BD-2 but fully retains the properties of a cognitive-stimulating agent. The design of hybrid compounds based on fullerene C60 and pharmacologically active groups can be one of the ways for optimizing therapeutically promising compounds.

Luminescent analysis of microsecond relaxation dynamics of viscous media

The dynamic properties of isobutanol are studied in a wide (90–350 K) temperature range by recording the relaxation shifts in the steady-state luminescence spectra of eosin and erythrosine and by kinetic phosphorescent spectroscopy invoking the Cole-Davidson model for dielectric relaxation. The characteristic dipole relaxation times and the activation energy of relaxation processes in the matrix in the temperature range of 140–170 K are determined from the correlation function of the dynamic Stokes shift of the phosphorescence spectrum of luminescent probe molecules.

Synthesis, photophysical properties, and photochemical activity of the water-soluble dyad based on fullerene С 60 and chlorin e 6 derivatives

Chlorin e6 derivative and water-soluble dyad resulting from covalent bonding of polyanionic fullerene С60 derivative to chlorin e6 derivative were synthesized and studied for spectral properties and photochemical activity. A considerable change in the absorption spectra and pronounced fluorescence quenching for the chlorin moiety included in the dyad were identified. The singlet excited state of chlorin is quenched via electron transfer from the excited chlorin to the fullerene core. A comparison of the photochemical activities of the test compounds in aqueous solutions showed a tenfold increase in the photochemical activity of the chlorin–fullerene dyad compared with free chlorin per absorbed light quantum.

Spectral Properties and Photodynamic Activity of Complexes of Polycationic Derivative of Fullerene C60 with Xanthene Dye Fluorescein

Using spectrophotometry and stationary and kinetic fluorimetry, we have shown that xanthene dye fluorescein forms complexes with polycationic derivative of fullerene in aqueous solutions mainly due to electrostatic interactions. It is found that efficient quenching of singlet excited states of dye occurs in the structure of these complexes due to the transfer of excitation or electron from dye to fullerene. As a result, the photodynamic activity of the newly formed complex is much higher than that of fluorescein and fullerene derivative. This effect makes it possible to predict the formation of new-generation hybrid photodynamic preparations using dyes excited only into a singlet state; as a result, directed searches for these dyes are significantly facilitated.

Revealing of the cation-binding sites on the surface of hemoglobin in its reaction with the NO donor, the nitrosyl iron complex {Fe2[S(CH2)2NH3]2(NO)4}SO4·2.5H2O

Deoxyhemoglobin (Hb) stabilizes the cationic nitrosyl iron complex with cysteamine {Fe2[S(CH2)2NH3]2(NO)4}SO4·2.5H2O (CysAm), by slowing down its hydrolysis. In the absence of Hb, the electrochemical detection of NO release in the course of the hydrolysis using a sensor electrode gave the rate constant of (5.2±0.2)·10−5 s−1. The release of NO is a reversible process, and the amount of released NO is 1.4% of the CysAm concentration. In the presence of Hb, NO is released much more slowly, and the reaction is more intense than that in the absence of Hb. The adsorption of CysAm by an Hb molecule results in NO release from the CysAm-Hb complex with a rate constant of 1·10−8 s−1. The analysis of the Hb surface revealed the possible location of the cation-binding sites, which reversibly bind the cationic CysAm complex. The kinetic parameters of NO release from CysAm in the absence and in the presence of Hb were studied by the kinetic modeling.