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A novel class of biologically active substances was created. These are hybrid macromolecu lar antioxidants (HMAO) based on hydrophilic polymers with chemically grafted sterically hindered phenols with different structural parameters. The antiradical activities of HMAO were assessed in reactions with 2,2 diphenyl 1 picrylhydrazyl and the corresponding sodium sulfonate in various solvents. The mechanism that explains the substantially enhanced activi ties of HMAO in water was proposed. The state of HMAO in solutions was studied by viscosim etry and photon correlation spectroscopy. HMAO were assayed in biological models.

We report on the synthesis and solution properties of novel tailor -made polymer conjugates, which are highly compelling for biomedical applications due to their antioxidant activity and the potential to fine-tune their thermosensitive properties. These conjugates consist of polyethylene glycol (PEG polymers containing antioxidant moieties, namely 3 -(3,5-di-tertbutyl-4-hydroxyphenyl)propionate or 2-benzamido-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylate, as end groups that differ in activity and hydrophobicity. It was shown that all of the synthesised conjugates have low critical solution temperatures (LCSTs) characteristic of type II polymers on a phase diagram. By simply varying the PEG molecular weight, the solution properties, including the LCST value, could be easily tuned across a broad temperature range of 20-90 ºC, providing an ideal method for the creation of thermosensitive polymers. It was also established that the LCST value and the polymer conjugate conformation depend on the antioxidant structure. From dynamic light scattering and small-angle X-ray scattering data, we were able to construct a complete sequence diagram of the conformational phase behaviour for the polymers with increasing temperature. It was observed that the conjugate conformation changes are the result of water shifting from a thermodynamically favourable solvent to an unfavourable one. This process then leads to compaction of the conjugate, followed by its aggregation.

Two series of conjugates of dextran and antioxidants from the class of sterically hindered phenols were prepared. The conjugates were characterized by the substitution degree of glycoside units, solubility in different solvents, intrinsic viscosity. The investigation of radical scavenging activity (RSA) of conjugates was carried out in their reactions with two free radicals — 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and sodium salt of 2,2‐diphenyl‐1‐picrylhydrazyl sulfonic acid (DPPH‐salt). The usage of water soluble DPPH‐salt enabled to estimate the RSA of the conjugates in water. It was shown that the rate constants of interaction of the DPPH‐salt and the conjugates were 10–30 times higher than this value for low‐molecular analogue of phenoxan. High RSA of the conjugates in water can be explained by large solvation shell formed due to high content of hydroxy groups in dextran.

The chitosan derivatives containing antiradical fragments in the polymer side chain have been synthesized by interaction of the partially quaternized chitosan(QCH) with gallic acid (GA). The antioxidative activity of the chitosan derivatives — QCH‐GA was investigated by thiobarbituric method. Introduction of GA fragment in amount of 2. 0 mass % in the structure of QCH resulted in appearance of pronounced antioxidative activity of the polymeric system contrary to initial chitosan for which this activity was equal to zero. It was found that QCH‐GA was a markedly higher effective inhibitor in a peroxidase — catalyzed oxidation of the model amine than the low‐molecular antioxidant — GA. Targetted chitosan modification resulted in a substantial raize of the polymeric antimutagenic (at γ‐irradiation) efficiency, which for QCH‐GA was equal to 92% in comparison with the protective effect of the initial chitosan — 42% (plant test‐system, barley seeds, γ = 15 Gr).

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Hybrid macromolecular antioxidants based on hydrophilic polymers with chemically grafted sterically hindered phenol fragments in aqueous solution exhibited considerably higher antiradical activity than that typical of compositions consisting of a polymer and low-molecular phenol analogs. The activity of the examined antioxidants is determined mainly by formation of supramolecular structures in solution, as well as by the position of the phenolic fragment inside or outside hydrate shell. An important structural factor is the size of the spacer connecting the redox-active phenol ring with the polymer. R = H, SO 3 Na.Synthesis of hybrid compounds containing functionally different fragments in a single structure is one of the most promising lines in the design of antioxidants of new generation for biology and medicine. Advantages of hybrid structures may be enhanced antioxidant efficiency, the possibility for its targeted delivery in a biosystem to be protected, controllable solubility, and reduced toxicity.Up to now, methods have been developed for chemical modification of hydrophilic bio-and synthetic polymers with derivatives of sterically hindered phenols. As a result, macromolecular antioxidants (conjugates) were obtained, which were characterized by different structural parameters: molecular weight (M) of the base polymer, concentration of phenol fragments in the polymeric chain (γ, mol %), and nature of the polymer-antioxidant linker [1][2][3][4]. Such polymers as dextran (I), hydroxyethyl starch (II), polyethylene glycol (III), and polyvinyl alcohol (IV) and functionalized derivatives of sterically hindered phenols, capable of forming covalent bonds with hydroxy groups in a polymer, β-(4-hydroxy-3,5-di-tert-butyl)-phenylpropionic acid A, 4-hydroxy-3,5-di-tert-butylcinnamic acid B, α-methyl-(4-hydroxy-3,5-di-tertbutyl)phenylacetic acid C, and derivatives of 4-hydroxy-3,5-di-tert-butylbenzyl alcohol D and 2-hydroxy-3,5-di-tert-butylbenzyl alcohol E, were used as co-reagents (Table 1). The amount of sterically hindered phenol fragments attached to a polymer was determined by UV spectrophotometry (by measuring the absorption intensity of the aromatic chromophore).The activity of macromolecular antioxidants in comparison with low-molecular analogs was estimated by measuring the rate constants for their reactions with

Chemical modification of polyethylene glycols by antioxidants belonging to the class of sterically hindered phenols is used to obtain water-soluble conjugates differing in the structure of the joined antioxidant and molecular weight. The inclusion of hydrophobic end groups in polyethylene glycol molecules leads to a decrease in the lower critical mixing point of the solution as compared to the original polymer. Dilute solution viscometry and light scattering are used to determine the molecular-mass characteristics of the polymers and the hydrodynamic radii of single conjugate molecules. The mass fraction of single molecules in aqueous solutions of the conjugates is greater than 95%. The aggregates are micellar-type particles whose core is formed by the hydrophobic moieties of sterically hindered phenols. It is shown that the antiradical activity of the antioxidants 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)-propionic acid and 3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid, which are used for the modification, differs only slightly, whereas the activity of the relevant conjugates increases significantly.