A Mechanistic Study of the Hydrolytic Stability of Poly(2-(dimethylamino)ethyl methacrylate)

Abstract

The hydrolytic stability of poly(2-(dimethylamino)ethyl methacrylate) was investigated and compared with the stability of its monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA), with 2-(dimethylamino)ethyl isobutyrate (DMAEIB), representing the repeating unit in the polymer, and with the related 3-(dimethylamino)propyl methacrylate (DMAPMA) (H0/pH range −0.5 to +12, at 37 °C, in aqueous solution). At pH < 3, the unsaturated DMAEMA and DMAPMA were more stable than the saturated DMAEIB. At pH 4−8, DMAEMA and DMAEIB were equally stable, but less stable than DMAPMA. This has been ascribed to a coordination of the protonated dimethylamino group and the ester carbonyl, rendering the ester more susceptible to nucleophilic attack of a hydroxyl ion. At alkaline pH (>pKa) no differences in stability between the compounds were found. P(DMAEMA), either in its free form or complexed to DNA, was substantially more stable to hydrolytic degradation than DMAEMA and DMAEIB. Fluorescence measurements performed with a copolymer of DMAEMA and dansyl ethyl methacrylamide showed that the dielectric constant (εr) experienced in the environment of the polymer backbone, was low (about 7). This microenvironment might be the reason for the hydrolytic stability of the polymer, since the hydrolysis of the monomer decreased substantially with decreasing εr of the medium. Accelerated degradation (80 °C, pH 1 and 7) of p(DMAEMA) and poly(2-(dimethylamino)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 εr in the environment of the acrylate backbone is higher than the εr in the environment of the p(DMAEMA) backbone.