Wpływ mikrootoczenia na mechanizm antyoksydacyjnego działania izotiocyjanianów

Recently, naturally occurying isothiocyanates (ITC) have attracted much attention due to their pharmacological properties – they are considered as chemopreventive and anticancer agents and protectors against inflammations. Sulforaphane (1-isothiocyanato-4-methylsulfinylbutane, SFN) and its analogs: erucin (1-isothiocyanato-4-methylsulfanylbutane, ERN) and erysolin (1-isothiocyanato-4-methylsulfonylbutane, ERS), are the most studied ITC. Biological properties of this group of compounds are due to the indirect antioxidant mechanism of action – instead of direct reduction of reactive oxygen species they are involved in the regulation/activation of Phase I and II enzymes. On the other hand, some reports suggest that these compounds are able to act as direct antioxidants, i.e., they can react with radicals including model radicals such as 2,2-diphenyl-1-picrylhydrazyl (dpph●), hydroxyl radical and superoxide radical anion. However, these properties have not been systematically determined and the pathway and reason for this kind of action have not been recognized yet. In contrast to relatively well understood mechanisms of action of common antioxidants like phenols, amines and carotenoids, the current knowledge on the mechanism of action of other classes of antioxidants, in particular ITC, is very limited. This dissertation describes results of comprehensive studies on the antiradical/antioxidant activity of selected group of ITC, including: synthesis of SFN and its analogs, kinetic studies on their reaction with dpph● model radical in a wide range of solvents with increasing polarities (stopped flow technique), investigations of a controlled autoxidation process in homogenous hydrocarbon model system in the presence of synthesized ITC (by measuring oxygen consumption), and investigations of thermal-oxidation processes of lipid matrices (linolenic acid, sunflower oil and soybean lecithin) in the presence of sulforaphane and its sulfide analog, erucin (DSC measurements). Bimolecular rate constants (ks) for the reaction with dpph● in series of solvents of various polarity indicated moderate reactivity of ITC with two compounds (ERS and SFN) reacting faster than other ITC. Basing on theoretical calculations for sulforaphane, mechanism of its antiradical action was proposed. Experiments were also carried out for autoxidation of cumene in the presence of ITC and the measured rates showed that the reaction of ITC with peroxyl radicals (LOO●) is not sufficiently fast (kinh < 102 M-1s-1) to break the propagation step of autoxidation (no induction period detected), therefore these compounds cannot be considered as chain-breaking antioxidants. The last part of the project involved study of non-isothermal oxidation of linolenic acid, sunflower oil and soybean lecithin by means of DSC technique. Obtained results indicated that sulforaphane and erucin exhibit antioxidant activity at higher temperatures (100 – 150 °C) due to formation of methanesulfenic acid and methylsulfinyl radicals, the species being good trapping agents for LOO●. The results of the project enabled to discover structure-activity-relationship of these ITC and to establish their mechanism of antiradical/antioxidant action. Determination of antiradical/antioxidant properties of sulforaphane and its analogs provides insight into the chemistry of ITC, extending the knowledge about these compounds in terms of chemistry of free radicals and antioxidants, and the potential role of ITC in food chemistry.