SYNTHESES AND TOXICITY OF MONOMERS AND POLYMERS CONTAINING 5-FLUOROURACIL

The monomers 1-(2-carbomethoxyacryloyl)-5-fluorouracil (CMAFU) and 1-(methacryloyloxyethyl)-5-fluorouracil (MAOEFU) were synthesized from 2,4-bis(trimethylsilyloxy)-5-fluoropyrimidine (BTMSF). Poly(MAOEFU) was obtained by radical polymerization with 2,2'-azobisisobutyronitrile (AIBN) in cyclohexanone at 60-degrees-C. Copolymerizations of CMAFU or MAOEFU with methyl methacrylate (MMA) or styrene (St) were carried out with AIBN at 60-degrees-C. The copolymer compositions were analyzed by infrared (IR) spectroscopy for poly(CMAFU-co-St) and poly(CMAFU-co-MMA), or by ultraviolet (UV) spectroscopy for poly(MAOEFU-co-MMA), respectively. The monomer reactivity ratios r1 and r2 were determined by the Kelen-Tudos method: r1 (CMAFU) = 0.01 and r2 (St) = 7.46; r, (CMAFU) = 0.01 and r2 (MMA) = 35.08; r1 (MAOEFU) = 0.77 and r2 (MMA) = 1.13. These values imply that the copolymerizations were significantly affected by the steric hindrances of monomers containing 5-fluorouracil (5-FU). Toxicity of the monomers and polymers synthesized against Drosophila melanogaster was investigated by the adult feeding method of Lewis and poly(CMAFU-co-St) > poly(CMAFU-co-MMA) > CMAFU > control and 5-FU > poly(MAOEFU-co-MMA) > MAOEFU > poly-(MAOEFU) > control.