New poly(anhydride-ester)s and the development of new melt condensation polymerization method and solution polymerization method for their syntheses

The thesis discusses the development of a series of degradable poly(anhydride-ester)s and synthesis methods thereof. Acyl chloride facilitated condensation polymerization and dehydrative coupling using (trimethylsilyl)ethoxyacetylene as the dehydrating agent are two of the novel aspects of this work.; Availability of polyanhydrides of desirable properties for controlled drug delivery is limited by the traditional condensation polymerization method by which they are usually synthesized, because of the low reactivity and harsh reaction conditions of this method. Poly(anhydride-ester)s are expected to be surface eroding and enrich the pool of available polyanhydrides. In this work, a series of symmetrical and unsymmetrical diacids are synthesized as monomers for the preparation of poly(anhydride-ester)s of appropriate thermal and degradation properties. Two new methods have been developed for effective preparation of poly(anhydride-ester)s from these monomers at conditions that are milder than that of the traditional melt polycondensation method. Polymerization of the diacid monomers was carried out using the three methods: (1) traditional melt condensation polymerization of acetylated diacids, (2) melt condensation polymerization facilitated by acyl chloride, (3) solution condensation polymerization using (trimethylsilyl)acetylene as the dehydrating agent.; The traditional condensation method failed to yield poly(anhydride-ester)s with appreciable results, due to the major side reactions as transacylation, transesterification and decarboxylation at all the attempted polymerization temperatures. The effects of these side reactions were greatly reduced in the system of acyl chloride facilitated condensation polymerization. The success of this method is due to the higher reactivity of carboxylic acid chlorides in exchange reactions, as well as the reduced transacylation reactivity of bulky acylated polymer chain ends in ring-forming transacylation reactions. Back-biting of the acylated polymer chain ends are believed to be the major cause of cyclization. (Trimethylsilyl)ethoxyacetylene was found to be an efficient dehydrating agent in dehydrative coupling of the monomers under mild conditions. High molecular weight products were obtained from certain monomers, whereas others show inclinations to forming cyclic anhydrides upon polymerization. Solvent hydrogen bonding is an important controlling factor for this method. Changing composition and structure of the repeating unit was shown to be an effective way to modify the monomer polymerization behaviors and properties of the polymers.