Improved synthesis of polystyrene–poly(ethylene oxide)‐heparin block copolymers

A novel procedure for the synthesis of block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic block of poly(ethylene oxide) and a bioactive block of nitrous acid‐degraded heparin was developed. Amino‐semitelechelic polystyrene was prepared by anionic polymerization of styrene in cyclohexane, using sec ‐butyllithium as initiator and N ‐(benzylidene)trimethylsilylamide as terminator. After purification using preparative column chromatography, polystyrene with one amino group per chain and a narrow molecular weight distribution was obtained. The terminal amino group was used in the coupling reaction with amino‐telechelic poly(ethylene oxide) using toluene 2,4‐diisocyanate to produce amino‐semitelechelic polystyrene‐poly(ethylene oxide) diblock copolymer (PS‐PEO‐NH 2 ). The block copolymer was purified by preparative column chromatographic separations and had a narrow molecular weight distribution. Approximately one amino group per chain was found. When methylene 4,4′‐diphenyl diisocyanate or hexamethylene diisocyanate were used as coupling agents low yields of PS‐PEO‐NH 2 were obtained. Polystyrene‐poly(ethylene oxide)‐heparin triblock copolymer was synthesized in a DMF‐H 2 0 (40:1, v/v) mixture by a coupling reaction of PS‐PEO‐NH 2 with nitrous acid‐degraded heparin, in which aldehyde groups react with the primary amino groups of PS‐PEO‐NH 2 at pH 7 in the presence of NaBH 3 CN via reductive amination. Using this procedure, 18–32% w/w heparin was incorporated, corresponding to ±1 PS‐PEO chain per heparin molecule. These procedures enable the synthesis of well defined heparin containing block copolymers, which will be further evaluated for thier blood compatibility.