Reactive Polyanions Based on Poly(4,4-dimethyl-2-vinyl-2-oxazoline-5-one-co-methacrylic acid)

The formation of reactive polyanions by semibatch copolymerization of 4,4-dimethyl-2-vinyl-2-oxazoline-5-one (VDMA) and methacrylic acid (MAA) by both free radical and photoinduced radical polymerization is described. The reactivity ratios of these two monomers were determined to be 1.36 and 0.41 for r 1(VDMA) and r 2(MAA), respectively, using 1H NMR spectroscopy. During the free radical copolymerization of a 50:50 VDMA:MAA copolymer (PMV50) in anhydrous DMSO or THF at 60 °C, up to 40% of the azlactone groups in the copolymer are hydrolyzed by water formed largely by conversion of methacrylic acid diads into cyclic anhydride. Storage in organic solutions leads to further transhydration, while solid PMV50 is stable for at least 6 months at room temperature. Increasing the VDMA comonomer content reduces this transhydration, likely through decreasing the incidence of methacrylic acid diads in the backbone. Alternatively, conducting the copolymerization at 20 °C using photoinitiation is also effective at suppressing this transhydration. The resulting reactive polyanions bind under physiological conditions to poly-l-lysine-coated calcium alginate hydrogel beads and spontaneously cross-link with the polyamine to form covalent networks of interest for long-term therapeutic cell encapsulation. This represents the first such use of a VDMA-containing polyanion in aqueous environments. The copolymers were characterized by 1H NMR, quantitative 13C NMR, 13C DEPT-135 NMR, and FT-IR spectroscopies as well as by elemental analysis.