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 (Mw/Mn ∼ 1.2−1.3) in either DMSO or DMSO/1,4-dioxane mixtures at 70 °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 1H 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 °C. Using water gave a fast, poorly controlled polymerization at 50 °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 °C with relatively low final polydispersities (Mw/Mn < 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 °C. Selected copolymers were cross-linked in aqueous solution at pH 9 by Michael addition using poly(ethylene glycol) diacrylate (PEGDA), as confirmed by 1H 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