Improved synthesis strategy of poly(amidoamine)s for biomedical applications: Catalysis by "green" biocompatible earth alkaline metal salts

Poly(amidoamine)s (PAAs) have received significant attention due to their good biocompatibility and fast biodegradation profile which gives these polymers high potential in biomedical applications. Conventional synthesis of PAAs via aza-type Michael addition reaction of primary amines to bis-acrylamides often proceeds slowly and takes several days, which does not allow fast and extensive screening of PAA libraries for their bioactivity. Current investigation was dedicated to the development of catalytic synthesis procedures in order to decrease the polymerization times. The salts of several transition metals, as well as earth alkali metals were studied for their catalytic activity in the polymerization reaction. It was found that the salts of earth alkali metals showed the highest potential in the catalysis of polymerization, whereas the salts of transition metals showed either no effect or even resulted in slowing down the reaction. In particular, the addition of CaCl2 to the reaction mixtures resulted in remarkable increase of the reaction rate as compared to the system without catalyst. PAAs synthesized by the conventional procedure and those obtained by using CaCl2 as a catalyst showed no difference in physico-chemical properties as well as in biological activity. The novel synthetic method for PAAs, using catalysts based on earth alkali metals, represents an attractive alternative to currently applied methods. Characteristics of earth alkali metals such as low toxicity and good biocompatibility make them especially useful in the preparation of these polymers for biomedical applications