No abstract

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).