A Mechanistic Study of the Hydrolysis of Poly[N,N-(dimethylamino)ethyl acrylates] as Charge-Shifting Polycations

Polycations are used extensively in applications ranging from enhanced oil recovery to biomaterials. Poly[N,N-(dimethylamino)ethyl acrylate] (PDMAEA) has attracted interest for biomaterial applications because of its rapid hydrolysis; however, the mechanism of hydrolysis and the conditions that affect degradation often appear amiss in the field. In this report, a detailed H-1 NMR spectroscopy study of the hydrolysis of PDMAEA was carried out between pH 0 and 14. In contrast to a widely held view, the rates of hydrolysis of this polymer were found to be highly pH-dependent with half-lives varying from years to minutes as a function of pH. The extent of hydrolysis was also found to be pH-dependent, with a distinct plateau at about 50-60% hydrolysis at pH 7 due to the electrostatic repulsion of anionic carboxylate groups and hydroxide. This was contrasted with the acid-catalyzed mechanism where hydrolysis of PDMAEA at pH 0.3 did not show a plateau in the extent of hydrolysis, reaching 88% hydrolysis after 8 days at 70 degrees C. In addition, the effects of neighboring functional groups on DMAEA hydrolysis in copolymers were explored, with anionic, neutral/hydrophilic, and cationic comonomers found to affect the rates of hydrolysis up to 20-fold at pH 7. Finally, two novel analogues of DMAEA with an additional dimethylamino group in different positions of the side chain were synthesized and polymerized to probe the effect of this added tertiary amine on the hydrolysis of the ester linkages. Poly[1,3-bis (dimethylamino)-2-propyl acrylate] (PBDMAPA) hydrolyzed more than 500 times faster at pH 7 than its linear isomer poly[2-((2( dimethylamino)ethyl)(methyl)amino)ethyl acrylate] (PDEMEA). These results further highlight the importance of the intramolecular interactions of the dimethylamino substituent of PDMAEA and the effect of proximity and steric hindrance of the amino group as well as neighboring functional groups of comonomers.