Direct synthesis of controlled-structure primary amine-based methacrylic polymers by living radical polymerization

We report the direct homopolymerization and copolymerization of a primary amine-based methacrylic monomer, 2-aminoethyl methacrylate (AMA), in its hydrochloride salt form by living radical polymerization. Linear PAMA homopolymer and AB diblock copolymers (where A = AMA and B = 2-(diisopropylamino)ethyl methacrylate, or DPA) were prepared with reasonably narrow polydispersities (M-w/M-n similar to 1.2-1.3) in either DMSO or DMSO/1,4-dioxane mixtures at 70 degrees C using cumyl dithiobenzoate (CDB) as a reversible addition-fragmentation transfer (RAFT) chain transfer agent. AMA monomer is highly unstable in its nonprotonated form, undergoing rapid internal rearrangement to afford 2-hydroxyethyl methacrylamide. PAMA homopolymer proved to be significantly more stable than AMA monomer, but nevertheless slow chemical degradation occurred over long time scales (days) in alkaline solution. Initial H-1 NMR studies confirm that (i) this PAMA degradation involves the elimination of 2-aminoethanol and (ii) at least some of its repeat units are converted into 2-hydroxyethyl methacrylamide units. AMA was also polymerized by atom transfer radical polymerization (ATRP) in methanol, water, and either 95:5 or 80:20 2-propanol/water mixtures. Polymerization was slow and incomplete in methanol at both 20 and 50 degrees C. Using water gave a fast, poorly controlled polymerization at 50 degrees C, while the 95:5 2-propanol/water mixture proved to be an inadequate solvent for PAMA at this temperature. However, an 80:20 2-propanol/water mixture gave slower, well-controlled polymerizations at 50 degrees C with relatively low final polydispersities (M-w/M-n < 1.25). Thus, this solvent mixture was used to prepare well-defined AMA-based diblock copolymers using poly(ethylene oxide)-based ATRP macroinitiators. Furthermore, statistical copolymerizations of AMA with either 2-hydroxyethyl methacrylate (HEMA), glycerol monomethacrylate (GMA), 2-hydroxypropyl methacrylate (HPMA), or 2-(dimethylamino)ethyl methacrylate (DMA) were conducted using ATRP in methanol at 20 degrees C. Selected copolymers were cross-linked in aqueous solution at pH 9 by Michael addition using poly(ethylene glycol) diacrylate (PEGDA), as confirmed by H-1 NMR studies. Shell cross-linked micelles with pH-responsive cores were also prepared from a RAFT-synthesized PAMA-PDPA diblock copolymer in water using PEGDA, as confirmed by dynamic light scattering studies.