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

Abstract

The formation of reactive polyanions by semibatch copolymerization of 4,4-dimethyl-2-vinyl-2-oxazoline-5one (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 1 H NMR spectroscopy. During the free radical copolymerization of a 50:50 VDMA:MAA copolymer (PMV 50 ) 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 PMV 50 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 1 H NMR, quantitative 13 C NMR, 13 C DEPT-135 NMR, and FT-IR spectroscopies as well as by elemental analysis.

Synthesis and properties of water‐soluble azlactone copolymers

“…The reactivity ratios of VDMA and MAA measured here for photo‐initiated polymerization at ∼10 °C in DMSO ( r 1 (VDMA) = 1.45 and r 2 (MAA) = 0.57) are in good agreement with our previously reported values ( r 1 (VDMA) = 1.36 and r 2 (MAA) = 0.41),13 obtained using the same analysis method but thermally initiated polymerization at 60 °C with AIBN, also in DMSO.…”

“…While the hydrolysis of residual azlactones helps avoid immunogenic protein binding, hydrolysis half‐lives that are too short can limit the extent of crosslinking achievable. Our previously reported p(VDMA‐ co ‐MAA) 50:50 copolymer had a hydrolysis half‐life of about 30 min in (4‐(2‐hydroxyethyl)‐1‐piperazine ethanesulfonic acid) (HEPES) buffered saline at about pH 7.4 13. That work also showed that photo‐initiated copolymerization at room temperature could be used to suppress an undesirable side‐reaction between the azlactone and MAA groups during copolymerization.…”

Designing catechol‐end functionalized poly(DMAm‐co‐NIPAM) by RAFT with tunable LCSTs

“…This ratio gives quantitative information on the propensity of an active center to react with either of the monomers; and when using terminal models, it is assumed to depend on the terminal monomeric unit. The reactivity ratios for the copolymerization were determined using Aguilar's method (eqs S1 and S2, terminal model, Supporting Information) based on the in situ 1 H‐NMR experiments (Fig. ) and solved via a nonlinear least square regression method using [DMAm] and [NIPAM] as variables.…”

“…Their study determined r NIPAM and r DMAm using a linear least square method (extended Kelen‐Tudos) for analyzing data obtained from batch experiments at high monomer conversions; whereas this study was based on in situ 1 H‐NMR data fitted via a nonlinear least square approach. The in situ 1 H‐NMR technique will provide better representation of the instantaneous monomers’ concentrations, while the nonlinear least square method is widely accepted as the most reliable method for determining reactivity ratios . Besides, the defining sequence of the copolymers as ideal with a tendency toward a pattern ( r DMAm × r NIPAM = 0.59–0.66), an expected implication is a compositional drift with tails richer in NIPAM units after much of the other monomer is consumed.…”

Contribution of polymeric materials to progress in xenotransplantation of microencapsulated cells: a review

“…It was demonstrated that either cross‐linked shells or cross‐linked cores are obtainable by adjusting the molar mass of the cross‐linker. Approaches based on chemical cross‐linking through complementary reactive groups attached to two oppositely charged polyelectrolytes were also investigated . Similarly, microbeads were prepared by ionotropic gelation of a combination of Ca‐alg and sericin as inner core followed by coating with chitosan and further cross‐linking with genipin .…”