Synthesis of a Monodisperse Polyamidoamine Through One-pot Lipase-catalyzed Regioselective Aminolysis and Michael Addition

MONSALVE, L. N.; FATEMA, M. K.; NONAMI, H.; ERRA-BALSELLS, R.; BALDESSARI, A.

Mainz, Alemania

Simposio; Frontiers in Polymer Science; 2009

Elsevier, Sponsored by IUPAC

The application of lipases in polymer synthesis is a well known fact. Polyesters and polyacrylamides are good examples of it. Lipases also show catalytic activity on Michael reactions. We have taken advantage of the double activity displayed by the lipase of Candida antarctica B (CAL B). We have performed the enzymatic synthesis of a biodegradable polyamidoamine from ethyl acrylate (1) and N-methyl-1,3-propanediamine (2) as starting materials. The polymeric material was prepared by the incubation of a 0.012M solution of reactants in either hexane or diisopropyl ether (DIPE) with CAL B for 72 hours in an orbital shaker at 30°C. Several solvents, concentrations, enzyme:substrate ratios, enzymes from different sources and temperatures have been tested in order to achieve optimal reaction conditions. The polyamidoamine have been characterized by: 1H and 13C, COSY, HSQC and HMBC NMR, FT-IR and UV-MALDI-TOF-MS. NMR experiments showed that the structure of the polymer obtained by this procedure, turned out to be very regular. This fact indicates that the behaviour of the lipase in the enzymatic polymerization is highly regioselective; aminolysis occurred exclusively on the primary amino group in 2 while the secondary amino group in 2 was the nucleophile in the Michael addition. UV-MALDI-TOF-MS experiments let to determine the Mn and Mw of the product and several structures in both ending groups of the polymeric chain: amide or carboxylic acid in R1 and amine or ether in R2. This is the first report of the synthesis of a polyamidoamine catalyzed by a lipase, affording a monodisperse, regular product in a highly regioselective fashion. This reaction could not be achieved previously by following the traditional synthetic methods. Regarding the biomedical applications of the polyamidoamines, the green and mild reaction conditions and the ease of handling of the enzymatic catalyst are obvious advantages of the present method.