It was found by the photocolorimetry method that in acidic media, compositions of natural carboxyl-containing phenols (antioxidants) with monosaccharides (synergists) show an antiradical synergistic effect in reactions with 2,2ʹ-diphenyl-1-picrylhydrazyl, the maximum value of which is typical for binary mixtures of sinapic, gentisic, and ferulic acids with galactose and mannose. It was shown by NMR spectroscopy and difference UV spectroscopy methods that the synergism mechanism consists in the formation of intermolecular hydrogen-bonded phenol-monosaccharide complexes in the ratio of 1:1. A combined model for selecting phenolic-saccharide compositions with high synergistic effect was proposed on the basis of quantum chemical DFT and regression analysis methods.

It has been established that the maximum synergistic effect (more than 100

It was found by the photocolorimetry method that binary compositions of protocatechic acid with monosaccharides (galactose, mannose) exhibit a pronounced antiradical synergistic effect in reaction with 2,2ʹ-diphenyl-1-picrylhydrazyl in acidic media. The synergistic properties of phenol-saccharide mixtures decrease with increasing pH of the medium. Using NMR spectroscopy and density functional theory, it was shown that the mechanism of synergism consists in the formation of intermolecular hydrogen–bonded phenol-monosaccharide complexes. The ionization energies of the donor and donor-acceptor complexes are lower than those of protocatechuic acid and hence the complexes react more actively with the radical compared to the initial antioxidant. Acceptor ion-molecular complexes with ionization energies higher than those of the reagents are less reactive.

It has been established that in an acidic medium with pH = 2, the rate of deactivation of the 2,2'-diphenyl-1-picrylhydrazyl radical in the reaction with natural phenolic compounds signifi-cantly increases in the presence of mono-and oligosaccharides compared to the additive action of the mixture. The maximum antiradical synergistic effect (65% and more) was shown by the binary compositions caffeic acid-maltotriose and dihydroquercetin-maltotriose in the ratio of 80:20% and 70:30%, respectively. Mixtures of saccharides with protocatechuic and pyrocatechuic acids turned out to be less active. For all groups of phenols, the synergistic activity increases with the transition from mono-to di-and trisaccharides. An increase in the medium pH from 2 to 9 actually leads to a complete leveling of antiradical synergism (up to 10%) in all studied phenol-saccharide mixtures, as well as to the appearance of antagonism effects at a high carbohydrate content in the composi-tion. Using NMR spectroscopy, it has been established that the mechanism of synergism consists in the formation of a phenol-saccharide donor-type hydrogen complex between the reactants, which interacts with the radical more effectively than the corresponding monomers. An increase in sugar percentage in the mixture, as well as an increase in the medium pH, leads to the growth of the content of H-complexes of the acceptor-type when phenol acts as a proton acceptor, thus the reducing properties of the complexes and the synergistic effect of the compositions in the reaction with hydrazyl radical will decrease. As a structural parameter associated with the synergistic effect of the composition, the ionization potential of the phenolic component of the mixture, calculated by the DFT method, was used. The established linear relationship between the maximum synergis-tic effect of the phenol-saccharide mixture and the ionization potential of phenols can later be used to form semi-empirical models for predicting the effectiveness of the antiradical action of natural phenol-carbohydrate synergistic compositions. A comprehensive study of phenol-saccharide mix-tures will expand the range of natural synergistic systems with expressed antiradical activity for practical use in pharmacy, perfumery, and the food industry.

As shown by photocolorimetry, NMR spectroscopy, and calculations based on the density functional theory, the synergistic antiradical effect of binary formulations of vegetable phenols with mono- and oligosaccharides in deactivation of 2,2ʹ-diphenyl-1-picrylhydrazyl in aprotic solvents consists in the formation of a phenol–saccharide hydrogen-bonded complex with more pronounced reducing properties compared to the components taken separately. In benzene, the synergistic effect for all the phenol–saccharide combinations studied is weak (no more than 30

A regression-classification algorithm for screening the antiradical activity of flavonoids and the related structures in the media with physiological pH and a specialized kinetic reaction scheme have been proposed. The algorithm is based on the combination of descriptor–activity single-factor linear regressions. The high predictive ability of the presented model has been confirmed by the low relative error (not exceeding 15%) in approximating the reactions rate constants of the control group of substances with nitrogen- and oxygen-centered radicals.

A regression–classification algorithm to screen natural hydroxybenzoic acids for antiradical activity in media with physiological pH was proposed. The algorithm is based on a combination of descriptor–activity two-variable linear regressions and a specialized kinetic scheme of reactions. The developed model solves the problem of simultaneous quantitative estimation of the activity of phenolcarboxylic acids and their division into groups of substances with high, medium, and low reactivities. The high predictive ability of the model was proven by studying the rate constants for the reactions of a reference group of substances (hydroxyacetophenones) with nitrogen- and oxygen-centered radicals at a calculated relative approximation error within 12%.

A relationship between the antiradical activity of flavonoids and the molecular descriptors related to the mechanism of their antiradical action was determined by single-variable linear regression analysis in the form of a semiempirical single-variable linear equation. The predictive ability of the derived model was evaluated using a test sample; the average error of approximation was no more than 8.5%. The obtained descriptor–activity relationship underlies the prediction of the antiradical properties of flavonoids and their similar structures in aqueous solutions with a physiological pH value of the medium.

Possible electron transfer mechanisms have been studied for the reaction of 2,2′-diphenyl-1-picrylhydrazyl with a number of natural hydroxybenzenes in aqueous buffer solutions at pH = 2–9 using the methods of spectrophotometry and quantum chemical calculations. In acidic media, electron transfer occurs from the molecular form of hydroxybenzene to the radical with subsequent loss of proton, whereas in alkaline media the electron is transferred from the phenolate ion to the radical, preceded by the proton elimination step. Realization of a specific mechanism is indicated by the dependence of the reaction rate constant on the pH of the media and by the presence of correlation between the Gibbs free activation energy, calculated using the Marcus equation and that determined experimentally.

Using the chronovoltammetric method, it has been shown that the reduction of oxygen on a mercury electrode in the presence of phenolcarboxylic acids in an acidic medium occurs as reversible electrode process followed by rate-limiting chemical reaction involving the hydroperoxyl radical. The rate constants of the phenolcarboxylic acids reaction with the radical have been calculated using the theory of electrode process followed by chemical reaction. The suggested reaction mechanism (electron transfer from the acid molecular form to the radical) has been confirmed by the correlation between the experimental rate constants and the ionization potentials of phenolcarboxylic acids simulated using the DFT method.

Методом хемилюминесценции определена реакционная способность гидроксибензойных кислот при взаимодействии с 2-амидинопропан-2-пероксильными радикалами, генерированными при термическом распаде азоинициатора 2,2ʹ-азобис(2-амидинопропан) дигидрохлорида в фосфатном буфере при рН=2. Установлена зависимость между антирадикальной активностью и молекулярными дескрипторами кислот, связанными с механизмом их антирадикального действия, в виде полуэмпирического линейного однофакторного уравнения. Полученная связь «дескриптор-активность» может быть основой для прогнозирования антирадикальных свойств фенолокислот и подобных им структур в водных средах. The reactivity of hydroxybenzoic acids in the reaction with 2-amidinopropane-2-peroxyl radicals generated by thermal decomposition of azoinitiator 2,2ʹ-azobis(2-amidinopropane)dihydrochloride in phosphate buffer at pH=2 was determined using chemiluminescence method. The relationship between the molecular acid descriptors, associated with the mechanism of their antiradical action, and antiradical activity in the form of a semi-empirical linear one-factor equation was established. The obtained «descriptor-activity» relationship can be used as a basis for predicting the antiradical properties of phenolic acids and similar structures in aqueous media.

Using the chronovoltammetric method it was shown that on a mercury film electrode in an acidic medium the reduction of oxygen to hydrogen peroxide in the presence of flavonoids is realized as a reversible electrode process followed by a first-order limiting chemical reaction with the participation of the primary product of the electrode reaction – the hydroperoxyl radical. For this type of reaction, in the case of reduction processes, the peak of potential shifts relative to the reversible half-wave potential in the direction of positive potentials. This shift is the larger then the higher the rate constant of the subsequent chemical reaction and the lower the sweep speed of the polarization voltage. To calculate the constants, the half-wave potential of oxygen electroreduction is determined without the addition of a flavonoid. Its value equals to –0.27 V and can be used both in acidic and alkaline media, since it does not change on mercury electrodes in the pH range of 1–9. The reaction rate constants of flavonoids with hydroperoxyl are a characteristic of their antiradical activity. The flavonone groups are the most reactive towards the radical compounds – morin and myricetin. For all studied compounds, the number of electrons participating in the limiting stage varies from 0.96 to 1. This indicates the occurrence of an elementary chemical act of a flavonoid with a radical and the absence of an effect on the kinetics of the investigated reaction of the products of the conversion of flavonoids. The applicability of the presented method for calculating the rate constants to reactions involving active oxygen forms is confirmed by the presence of a high correlation between the data obtained and the reaction rate constants of flavonoids with 2,2′-diphenyl-1-picrylhydrazyl radical.

The kinetics and mechanisms of the reactions of some natural phenylpropanoids from the group of hydroxycinnamic acids with the stable radical 2,2'-diphenyl-1-picrylhydrazyl in polar nonionizing media were studied by kinetic and spectrophotometric methods. The kinetic and stoichiometric parameters of the reaction were determined. The magnitude of the deuterium isotope effect shows that in polar solvents with low ionizing ability (dimethylsulfoxide), the reaction proceeds by the electron transfer mechanism followed by proton transfer. A similar mechanism of the antiradical action of hydroxycinnamic acids is possible in highly acidic aqueous media.

The presence of a synergistic effect of binary mixtures of quercetin–monosaccharide in the model reaction with the 2,2'-diphenyl-1-picrylhydrazyl radical in deoxygenated ethanol was established. It was shown that the studied carbohydrates related to the tetrose, pentose and hexose groups exhibit a synergistic effect to some extent enhancing the anti-radical effect of quercetin. The synergistic effect of the mixture is determined by the number of hydroxyl substituents and by the presence of aldehyde or ketone groups in carbohydrate molecules. The synergistic compositions of quercetin with glucose and galactose in the ratio of 60:40% showed the highest antiradical activity. The maximum synergistic effect of the mixture is 75%. It is achieved due to the fact that, firstly, when dissolved in water, quercetin transforms into a tautomeric diketo form where hydrogen bonds form between its carbonyl groups and hydroxy groups of the monosaccharide, promoting the formation of molecular complexes, improving solubility of flavonoid in water and the manifestation of a synergistic effect in a mixture with carbohydrate. Secondly, reducing carbohydrates are able to restore oxidized forms of quercetin, which is confirmed by the great synergistic effect of aldose in comparison with ketoses, regardless of the number of hydroxy groups in the molecule. The synergistic effect of the quercetin–monosaccharide compositions, established in a model reaction with a hydrazyl radical, was compared to that in the autoxidation process of cottonseed oil. In the reaction with the peroxy radicals of cottonseed oil, the synergistic effect of the quercetin monosaccharide compositions increases up to 300% only for sugars capable of reducing quercetin radicals and reacting with air oxygen, reducing the steady-state concentration of peroxy radicals in the system.

Using the spectral method, the rate constants of natural phenolcarboxylic acids reaction with the radical 2,2'-diphenyl-1-picrylhydrazyl in benzene at a temperature of 293±2 K were determined. It is established that the reaction corresponds to the second-order kinetic equation and proceeds by the mechanism of the hydrogen atom transfer. This confirmed by the presence of the deuterium isotope effect. The parameter, affecting the proceed of this mechanism in a non-polar medium, is the energy of the homolytic rupture of the weakest phenolic O–H bond in the phenolcarboxylic acid molecule, calculated using the quantum-chemical methods. Changes in the strength of phenolic O–H bonds in an acid molecule lead to corresponding changes in their reactivity with respect to the hydrazyl radical. It is seen that the compounds with low bond strengths of functional groups – 3 pyrogallolcarboxylic and gallic acids, methyl- and ethyl- gallate – showed the most antiradical activity. According to the calculated and experimental data, a semiempirical linear single-factor equation is proposed. This equation describes the relationship between the antiradical activity of phenolic acids and the descriptor of their structure and allows to predict the reactivity of the antioxidant in lipid-like media. The applicability of the proposed model was proved by studying the control group of hydroxyacetophenones which belong to plant phenol compounds. According to the forecast, 3,4- and 2,5-hydroxyacetophenones can be recommended as potential effective antioxidants in non-polar environments. The unit relative deviations of the predicted rate constants from their experimental values vary from 2 to 9% with an average approximation error equals to 7.9%, which indicates a good selection of the linear model.

Fourier-transform IR and NMR spectroscopy are used to show that, in the reaction with 2,2'‑diphenyl-1-picrylhydrazyl radical, the secondary products of natural phenol conversion are dimeric compounds formed by recombination of phenoxyl radicals. According to thermodynamic parameters of the reaction calculated by the DFT method the most stable structures in the studied system are CC dimers. The resulting dimeric phenols show a lowered antiradical activity compared to the original phenol, which ensures a prolonged effect of the original antioxidant and enhances its overall antioxidant activity in radical oxidation reactions.