Synthesis of hydrophilic polar supports based on poly(dimethylacrylamide) via copper-mediated radical polymerization from a cross-linked polystyrene surface: Potential resins for oligopeptide solid-phase synthesis

A series of cross-linked polystyrene-based resins, Wang, Merrifield, and primary amino functional beads, have been transformed into initiators for transition-metal-mediated radical polymerization. Wang and amino functional resins have been condensed with 2-bromoisobutyryl bromide to give approximately quantitative conversion to initiator groups as monitored by FTIR and gel-phase C-13 NMR spectrometry. In each case efficient polymerization of N,N-dimethylacrylamide (DMAc) has been demonstrated. Polymerization occurs with the RuCl2(PPh3)(3) system in conjunction with Al((OPr)-Pr-i)(3) with the reaction proceeding most efficiently with a toluene/ethanol solvent mixture which gives the best swelling of the composite particle. Surprisingly, copper(I) bromide with the pyridine imine type catalysts also led to efficient polymerization. Polymerization proceeds effectively directly from chloromethyl functional Merrifield resins given a 75% increase in weight at 130 degreesC after 55 h. Yields are significantly greater for derivatized Wang resins giving over 1000% weight increase under similar conditions. Gel-phase NMR shows the grafted polymer. Statistical copolymerization of DMAc with N-acryoyl sarcosine methyl ester (ASME) proceeds under the same conditions to give even higher yields at over 1500% weight increase. Gel-phase NMR shows two different amide carbonyls at 175.1 and 176.1 ppm along with the ester carbonyl from incorporation of ASME at 170.1 ppm. Hydrolytically more stable resins are formed from the amide derivatized initiator used under a range of conditions. Scanning electron microscopy of the resins shows spherical products with little observable breakage. Catalyst is removed from the resin using an organic soluble EDTA salt. These resins have potential in continuous solid-phase oligopeptide synthesis.