Studies of the esterification of dextran: routes to bioactive polymers and graft copolymers

Abstract

Problems associated with the esterification of dextran as a means of coupling bioactive molecules or introduction of functionality suitable for graft polymerization are considered. In particular, the importance of eliminating side-reactions which incorporate into dextran unwanted residues, e.g. groups containing nitrogen, is emphasized and practical techniques for minimizing this are described. We have developed a formamide-based solvent suitable for esterification with the aid of dicyclohexyl carbodiimide (DCC) and carbonyl di-imidazole (CDI) as coupling agents. The preferred catalyst is p-pyrrolidinopyridine. CDI has the advantage of enabling dimethylsulphoxide to be used as solvent for dextran and other hydroxylic polymers without inducing oxidation of hydroxyl groups. This coupling agent is flexible and offers a choice of two routes to esterification, each having its merits. We have optimized conditions for coupling by use of butyric acid as model. Esterification of dextran has been employed in the preparation of soluble bioactive macromolecules by coupling the anti-platelet agent (I) and also in the synthesis of graft copolymers via introduction of 2-bromopropionate groups. Crosslinking of dextran and the polymerization of dipyridamole have been effected by use of CDI.