ABSTRACT
This work is a brief review of research conducted at the Emanuel Institute of Biochemical Physics of Russian Academy of Sciences (IBCP) reflecting modern trends in the chemistry of hindered phenols (HP).
The greatest attention is paid to hybrid antioxidants based on HP combining in one molecule variously functional fragments: a redox-active phenolic core and a structural element that provides biocompatibility, transport properties, the ability to interact with cellular structures, increased antioxidant activity, etc.
Hybrid antioxidants are represented by two classes of antioxidants: “float” compounds containing a charged onium anchor and lipophilic long chain alkyl radical-float, as well as hybrids of HP with hydrophilic biological and synthetic polymers (dextrans, hydroxyethyl starch (HES), polyvinyl alcohol (PVA), and oligomeric polyethylene glycols). A comprehensive study was conducted, including the development of synthesis methods and the evaluation of antioxidant activity in model reactions with free radicals, 4diphenylpicrylhydrazyl, and its water-soluble sulfonate salt derivative. Water shell of the macromolecule plays an important role in the activity of hybrid antioxidants. This activity depends on the location of the redox active phenolic core inside or outside the shell determined by the length of the spacer separating the phenolic core from the polymer chain. Hybrid antioxidants with a different number of HP fragments grafted to the polymer were synthesized and studied in organic, water-organic, and aqueous media.
A special section is devoted to the unique example of a diatomic HP with symmetrically shielded hydroxyl groups, the 3,6-di-tert-butyl catechol (3,6-Cat) and its redox conjugated derivatives, semiquinone, and o-quinone.
This triad demonstrates the properties of a universal antioxidant capable of interacting with various active oxygen forms, including singlet oxygen, as well as the unusual reactivity associated with the ease of electronic transfer in the triad, chelating effect of neighboring hydroxyl/carbonyl groups, and sensitivity to the action of pressure and shear deformation.
The triad of 3,6-Cat – semiquinone – o-quinone also demonstrates a cascade mechanism of the antioxidant activity, in which the total activity is provided not only by the original compound, but also by the products of its conversions in situ. Examples of such a mechanism were also found in the study of antibacterial activity (ABA) of HP. A correlation between antibacterial and antiradical activity was revealed. A special part of the review deals with examples of syntheses based on HP related to the regioprotective function of tert-butyl groups.
