Antioxidant Activity of Diatomic Phenols

ISSN 1990-7931, Russian Journal of Physical Chemistry B, 2022, Vol. 16, No. 1, pp. 50–57. © Pleiades Publishing, Ltd., 2022. Russian Text © The Author(s), 2022, published in Khimicheskaya Fizika, 2022, Vol. 41, No. 2, pp. 12–19. KINETICS AND MECHANISM OF CHEMICAL REACTIONS, CATALYSIS Antioxidant Activity of Diatomic Phenols I. F. Rusinaa, *, T. L. Veprintsevb, and R. F. Vasil’evb a Semenov Federal Research Center of Chemical Physics, Russian Academy of Sciences, Moscow, Russia b Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia *e-mail: Received July 27, 2021; revised August 16, 2021; accepted August 20, 2021 Abstract—Nine compounds are studied for antioxidant activity, including those from the class of catecholamines containing 3,4-hydroxyphenyl (catechol) as a common structural fragment, which imparts antioxidant properties to the compounds in the reactions of hydrocarbon substrate oxidation. The antiradical activity is determined by the chemiluminescent method by the interception of peroxyl radicals in the model reaction of the initiated oxidation of ethylbenzene (RH). The mechanism of the inhibition of chain oxidation processes by diatomic phenol compounds is provided by the presence of two active hydroxy groups with a possible intramolecular hydrogen bond, leading to a weakening of the О–Н bond and a high rate constant of hydrogen abstraction in the reaction with peroxyl radicals (kinh). This reaction is dominant and determines the inhibitory activity of antioxidants in oxidation processes. The maximum inhibitory activity is shown by 3,5- and 3,6-di-tert-butylpyrocatechins, dopamine, and epicatechin. Keywords: chemiluminescence, catecholamines, antioxidants DOI: 10.1134/S1990793122010274 of the most promising ways to create new drugs for the treatment of diseases such as polyneuropathy of various etiologies, Parkinson’s disease, Alzheimer’s, and complications after a disease caused by ther coronavirus infection COVID-19. Catecholamines are a group of biogenic amines containing 3,4-dihydroxyphenol (catechol) as a common structural fragment, which gives these compounds the status of antioxidants in the oxidation of organic compounds. Catecholamines are water-soluble compounds that function as natural neurotransmitters in living organisms (adrenaline, norepinephrine, dopamine) [1–6]. This circumstance raised the problem of determining the key kinetic characteristics of the antioxidant action and developing convenient and reliable instrumental methods for their determination. To study the kinetics of oxidative processes, including those involving antioxidants, it is most convenient to use chemiluminescent methods [7–15]. In this study, we consider the possibilities of using the chemiluminescent method based on measuring the intensity of chemiluminescence (CL) accompanying the initiated oxidation of hydrocarbons to obtain quantitative characteristics of the antiradical activity of diatomic phenols: the rate constants of the reaction of a peroxide radical with an inhibitor molecule (kinh) and stoichiometric inhibition coefficient (f). The structural formulas of the compounds studied in this work are shown in Fig. 1. INTRODUCTION Diatomic phenols containing OH groups in the ortho-position are widespread in wildlife. Fragments of pyrocatechol are present in many flavonoids. Such compounds play an important role in inhibiting unwanted oxidative processes in living systems, protecting them from the effects of oxidative stress. There is substantial interest in studying polyphenols due to the ability of these compounds to reduce the risk of atherosclerosis, cancer, and cardiovascular diseases. Until the 1990s, there was practically no information in the literature on the antioxidant and biological properties of sterically complicated diatomic phenols of the catecholamine group. Recently, a great deal of attention has been paid to determine the antioxidant activity (AOA) of these compounds. A variety of approaches are used in the research to assess the AOA. However, the results of many works seem to be ambiguous. The AOA of natural compounds and their analogs is most often studied in heterogeneous systems that mimic the structure of a cell of a living organism: micelles and liposomes. However, the AOA determined under these conditions depends on various factors. In order to exclude the influence of these factors, it is necessary to carry out studies on the oxidation of model systems in a homogeneous system. The study of the AOA of polyphenols upon inhibition of oxidation in solution seems to be relevant. The search for drugs among compounds of diatomic phenols and their derivatives seems to be one 50 ANTIOXIDANT ACTIVITY OF DIATOMIC PHENOLS OH 51 OH OH HO HO OH Сatechol Hydroquinone 4-tert-pyrocatechol OH HO OH OH 3,5-di-tert-butyl-pyrocatechol 3,6-di-tert-butyl-pyrocatechol OH HO NH2 HO HO NH2 HO Norepinephrine Dopamine OH HO HO NH OH O OH HO OH OH Adrenalin Epicatechin Fig. 1. Structural formulas of the studied diatomic phenols. EXPERIMENTAL In this study we investigated five compounds of diatomic phenols, homologs of pyrocatechol, synthesized and provided by the laboratory for the synthesis of complicated phenols (Institute of Biochemical Physics, Russian Academy of Sciences (IBCP RAS)), and four compounds of a number of natural catecholamines (Fluka) for antiradical activity in relation to peroxyl radicals leading the oxidation chain. The antiradical properties of diatomic phenols were investigated by the effect of inhibition of the liquid-phase oxidation of ethylbenzene (RH), initiated by the thermal decomposition of the initiator 2,2'-azobisisobutyronitrile (AIBN). The initiator was recrystallized twice from ethanol, followed by drying in a vacuum to a constant weight. The solvent chlorobenzene (Merck) and the model hydrocarbon ethylbenzene (Aldrich, 99.8%) were used without preliminary purification. The oxidizing reaction mixture (5 mL) was placed in a chemiluminometer cuvette thermostated at 50°C and saturated with oxygen by bubbling air with an injection RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY B compressor. Weak primary luminescence (triplet-singlet emission of light by an excited product, acetophenone) was enhanced by transferring energy to an effective phosphor, 9,10-dibromoanthracene (DBA), and recorded on a chemiluminometer with an H7467 photosensor module (Hamamatsu, Japan) with an RS-232C interface. The initiated oxidation rate, Wi, was calculated using the ratio Wi = 2 fcell k0 [ AIBN] = 1.2 × 1.58 × 1015 exp(−30800 RT ) [ AIBN] , (1) where fcl is the exit of radicals from the cell (fcl = 0.6), and k0 is the rate constant of the decomposition of the initiator, which is practically independent of the nature of the solvent [16–21]. The initiation rate, Wi, was additionally monitored and was measured directly in the reaction mixture before and after the experiment on the CL kinetics aft (...truncated)