A MECHANISTIC STUDY OF THE HYDROLYTIC STABILITY OF POLY(2-(DIMETHYLAMINO)ETHYL METHACRYLATE)

The hydrolytic stability of poly(2-(dimethylamino)ethyl methacrylate) was investigated and compared with the stability of its monomer 2-(dim ethylamino)ethyl methacrylate (DMAEMA), with 2-(dimethylamino)ethyl is obutyrate (DMAEIB), representing the repeating unit in the polymer, an d with the related 3-(dimethylamino)propyl methacrylate (DMAPMA) (H-0/ pH range -0.5 to +12, at 37 degrees C, in aqueous solution). At pH < 3 , the unsaturated DMAEMA and DMAPMA were more stable than the saturate d DMAEIB. At pH 4-8, DMAEMA and DMAEIB were equally stable, but less s table than DMAPMA. This has been ascribed to a coordination of the pro tonated dimethylamino group and the ester carbonyl, rendering the este r more susceptible to nucleophilic attack, of a hydroxyl ion. At alkal ine pH (> pK(a)) no differences in stability between the compounds wer e found. P(DMAEMA), either in its free form or complexed to DNA, was s ubstantially more stable to hydrolytic degradation than DMAEMA and DMA EIB. Fluorescence measurements performed with a copolymer of DMAEMA an d dansyl ethyl methacrylamide showed that the dielectric constant (eps ilon(r)) experienced in the environment of the polymer backbone, was l ow (about 7). This microenvironment might be the reason for the hydrol ytic stability of the polymer, since the hydrolysis of the monomer dec reased substantially with decreasing epsilon(r) of the medium. Acceler ated degradation (80 degrees C, pH 1 and 7) of p(DMAEMA) and poly(2-(d imethylamino)ethyl acrylate), p(DMAEA), showed that p(DMAEA) was more sensitive to hydrolysis. This can be explained by the assumption that, due to the lack of the methyl group, the epsilon(r) in the environmen t of the acrylate backbone is higher than the epsilon(r) in the enviro nment of the p(DMAEMA) backbone.