Synthesis, characterization, and antitumor activity of poly(maleic anhydride-co-vinyl acetate-co-acrylic acid)

The ternary copolymerization of maleic anhydride (MA), vinyl acetate (VA), and acrylic acid (AA) [P(MA-co-VA-co-AA)], which is considered to be an acceptor-donor-acceptor system, was carried out in 1,4-dioxane with benzoyl peroxide as an initiator at 70 degrees C tinder a nitrogen atmosphere. Constants of complex formation for the monomer systems in the study were determined by UV-visible (hydrogen-bonding complex) and H-1-NMR (charge transfer complex) methods, respectively. The results show that polymerization of the P(MA-co-VA-co-AA) system proceeds by an alternating terpolymerization mechanism. It is shown that the synthesized copolymers have typical polyelectrolyte behavior, ability for reversible hydrolysis-anhydrization reactions, and semicrystalline structures. In these cases, including radical polymerization, and formation of semicrystalline structures, the hydrogen-bonding effect plays a significant role. The in vitro cytotoxicities of the synthesized terpolymer and alternating copolymer were evaluated using Raji cells (human Burkitt lymphoma cell line). The antitumor activities of prepared anion-active copolymers were Studied using methyl-thiazol-tetrazolium colorimetric assay and 50% of the cytotoxic dose of each copolymer and terpolymer were calculated. Hydrolyzed P(MA-co-VA-co-AA) and P(MA-alt-AA) copolymers have sufficiently high antitumor activity, which depends on the amount of hydrogen-bonding carboxylic groups and their regular distribution in the side chain of functional macromolecules. (c) 2006 Wiley Periodicals, Inc.