L. N. Shishkina

Membrane-protective properties of isobornylphenols-a new class of antioxidants

The membrane protective and membrane active properties and the antioxidative activity of new semisynthetic antioxidants—isobornylphenols were studied. The presence of oxidant and cytotoxic properties of the compounds were evaluated considering the degree of hemolysis of erythrocytes, either spontaneous or induced by hydrogen peroxide. All the studied compounds were found to have significant antioxidative activity in certain conditions. But their capacity to protect membrane erythrocytes from oxidative stress substantially depended on the structure and concentration of the compound. The highest membrane protective activity was observed for 2,6-diisobornyl-4-methylphenol, which has isobornyl in both of its ortho-positions. Scanning electron microscopy of blood erythrocyte surface architectonics confirmed the ability of the studied compounds to interact with the cell membrane and to change its structure. A relationship between erythrocyte morphological transformation according to bilayer-couple hypothesis depending on isobornylphenols membrane behavior and the cytotoxic effect of certain compound high concentrations reflected in low membrane protective activity in the model cell system was shown. The data obtained allow us to conclude that the biological activity of isobornylphenols is due to both their antioxidative properties and their ability to interact with the cell membranes.

Lecithin influence on the effectiveness of the antioxidant effect of flavonoids and α-tocopherol

Influence of the widely used food additive lecithin on the effectiveness of the inhibiting effect of the natural antioxidants (quercetin, dihydroquercetin, and α-tocopherol) has been studied in dependence on the rate of free radicals generation in the model oxidation reactions. It has been found that during the initiated and autoxidation of methyl oleat, lecithin decreased the antioxidant effectiveness of flavonoids. The effect value increased with the lecithin concentration increase. Under similar conditions while oxidation inhibiting by α-tocopherol and lecithin mixtures, the latter did not influence the tocopherol antioxidant effectiveness (additivity) or led to the increase of the inhibition effectiveness (synergism).

Inhibiting activity of isocamphyl substituted phenols and their mixtures with 2,6-di- tert -butylphenol in the initiated oxidation of ethylbenzene

The stoichiometric coefficients of inhibition and rate constants for the reaction of several terpenephenols (isocamphyl substituted phenols) with ethylbenzene peroxy radicals were measured. Their reactivity was found to increase as the number of alkyl substituents grew and decreased with an o-alkoxyl compared with o-alkyl substituent because of the formation of an intramolecular H-bond. In spite of similar antiradical activities of terpenephenols with isocamphyl and isobornyl substituents, the reactivities of phenoxyl radicals formed from them in the interaction with sterically hindered phenol molecules are substantially different. They are higher for isocamphylphenols with substituents turned with respect to the aromatic ring plane.

Kinetic characteristics and physicochemical properties of isobornyl phenols with different alkyl substituents in the ortho -position

The rate constants were measured for the reactions of isobornyl phenols (IBPs) containing methyl and tert-butyl substituents in the ortho-position with peroxide radicals in the initiated oxidation of ethylbenzene. The IR spectra of IBPs were analyzed, and the influence of IBPs on phosphatidylcholine aggregation in hexane was studied. The influence of the structure of substituents on the kinetic characteristics and physicochemical properties of the studied phenols is ambiguous. The data obtained indicate the competitive influence of the donor ability and shielding effects of the alkyl substituent in the ortho-position to the hydroxy group on the kinetic characteristics and physicochemical properties of IBPs.

Tertiary aminomethylphenols and methylene bisphenols with isobornyl substituents in the reaction with diphenylpicrylhydrazyl and peroxy radicals in ethylbenzene

The effect of the structure of aminomethylphenols and methylene bisphenols with isobornyl substituents on their reactivity in interactions with peroxy radicals in ethylbenzene and with 1,1-diphenyl-2-picrylhydrazyl (DPPH) is studied. Isobornylphenols with o-aminomethyl substituents, as opposed to p-aminomethyl derivatives, were found to possess rather low activity in the initiated oxidation of ethylbenzene, due to the formation of intramolecular hydrogen bonds between the hydrogen atom of the OH group and the nitrogen atom of the aminomethyl substituent. An increase in activity of o-aminomethyl-substituted phenols with increasing polarity of the medium is observed in the reaction with DPPH. The reaction rate constants for the interaction between two isomeric 2,2′- and 4,4′-methylene-bisphenols having isobornyl moieties and ethylbenzene peroxy radicals are measured. The ratio between activities of the first and second OH groups in 2,2-methylene-bisphenol is shown to be close to 50.

Surface active properties of isobornylphenols in systems with different degrees of complexity

Interrelations between the structure of the semi-synthetic phenolic antioxidants — isobornylphenols and their surface active properties were studied in the chemical (the lecithin aggregation in hexane) and biological (the incubation with the blood erythrocytes) model systems. It has been shown that all studied compounds are able to affect the lecithin aggregation in hexane: the share of the main fraction of the L micelles decreases with increasing the share of particles of greater size. The effect substantially depends on hindered OH group and the presence of the intramolecular hydrogen bond in molecule. The cytotoxic properties of isobornylphenols (the concentration is 100 μM) are predominantly due to the molecule structure. The interrelation between the aggregate size of the main fraction of L in the presence of the studied compounds and the discocyte share during mice blood erythrocyte incubation in their presence for 4 h is revealed. Thus, this provides the possibility to assume that the ability of the different biological active substances to affect the lecithin aggregation in non-polar solvent could be used as a model system for the initial assessment of their surface active properties.

Effect of physicochemical properties of murine liver lipids on the interrelation between the parameters of their composition

The effect of properties of liver lipids on the interrelation between the contents of different lipid fractions has been studied on nine groups of intact SHK female mice. To reveal interrelations, lipids were divided into four groups depending on their antioxidative activity, prooxidant properties, antiperoxide activity, and the content of peroxide in lipids. The data obtained indicate that the physicochemical properties of lipids affect the biosynthesis and degradation of phospholipids, which plays a significant role in the origination of consequences under the action of unfavorable factors on biological objects having the different intensity of oxidative processes.

Effect of the nature of phospholipids on the degree of their interaction with isobornylphenol antioxidants

The parameters of complexation between natural phospholipids (lecithin, sphingomyelin, and cephalin) with antioxidants of a new class, isobornylphenols (IBPs), were determined by UV and IR spectroscopy. The self-organization of phospholipids (PLs) was studied depending on the structure of IBPs by dynamic light scattering. The nature of phospholipids and the structure of IBPs was found to produce a substantial effect both on the degree of complexation and on the size of PL aggregates in a nonpolar solvent. Based on the obtained data it was concluded that the structure of biological membranes mainly depends on the complexation of IBP with sphingomyelin.

A new approach to analysis of participation of oxidative processes in regulation of metabolism in animal tissues

A new approach to the analysis of the oxidative processes participated in regulation of metabolism in norm and the assessment of the biological consequences under the action of damaging factors of different nature and intensity for animal groups is suggested using the analysis of interrelations between the different parameters of the physicochemical regulatory system of the lipid peroxidation in tissues of the laboratory mice (the phospholipid composition, amounts of the oxidation products in lipids) by changes of the scale and direction of interrelations between the reciprocal parameters of the lipid peroxidation system in norm.

[Interrelation between structural state, physicochemical properties and lipid composition in microbial cells].

We performed complex investigations of antioxidant properties and the lipid composition of the five gram-negative bacteria depending on the cultivation season. Structural state, the lipid composition and physicochemical properties of lipids of the three gram-negative bacteria (Renobacter vacuolatum, Flectobacillus major WKM 869, Pseudomonas fluorescens) during their growth and mycelium of four species of the xylotrophic basidiomycetes (Panus tigrinus IBK-131, Fomes fomentarius M71, Laetiporus sulfureus M131, Piptoporus betulinus M60) during the lag phase were also studied. Changes in the composition of the lipid component in the studied bacteria led to considerable structural rearrangements in their membrane system during the growth of bacteria. It is shown that more hydrophilic regions of the lipid component are of paramount importance in maintaining the fluidity of the entire lipid bilayer in the basidiomycete mycelium. The scale and direction of the revealed interrelations between rotational correlation times of probes and the lipid composition depend both on localization of the probe in membrane and the composition and physicochemical properties of the microorganism lipids.