Synthesis and characterization of biocompatible PEGylated poly(alpha-amino acid) random and block copolymers for application to solid surfaces

The focus of this work is on the synthesis of poly(amino acid)s by N-carboxyanhydride (NCA) ring opening polymerization (ROP) that is initiated by primary amines (small molecules and macromers) in the presence of urea. Urea interrupts the formation of hydrogen bonds during the early stages of chain growth, thus suppressing the formation of the beta-sheet secondary structures.;Experiments were conducted with side chain protected lysine, cysteine, and glutamate N-carboxyanhydrides to demonstrate that beta-sheet formation is present in hexylamine initiated homo-oligomers (< 10mers). It was observed that all urea free synthesized oligomer of N-hexylamine-poly(cysteine) retained a beta-sheet structure regardless of oligomer length. Synthesis utilizing urea caused a reduction in beta-sheet formation, and an increase in disordered oligomer chains. N-hexylamine-poly(L-lysine) and N-hexylarnine poly(L-glutamate) showed beta-sheet secondary structure as 4mers and 5mers, respectively. The oligomers developed alpha-helices, as described in literature (≥ 12 mers+/-1 for L-lysine and 9mers+/-1 for L-glutamate) at longer chain lengths of 13mers and 11mers for N-hexylamine-poly(L-lysine) and N-hexylamine poly(L-glutamate) respectively.;PEGylated poly(amino acid)s (paas) were successfully synthesized in the presence of urea, yielding products that were of desired molecular weight and architecture. Random and block copolymers were initiated by alpha-amino-o-methoxy poly(ethylene glycol) (Mw 5kDa) and synthesized to yield polymers with amino acid repeat units totaling between 60 and 120 repeat units. Gel permeation chromatography (GPC) and proton nuclear magnetic resonance (¹HNMR) experiments showed that living polymerization was achieved and yielded polymers with polydispersity indexes (PDI) between 1.13 and 1.34. Higher PDIs were observed consistently in the random copolymers indicating that a blocky nature could have been induced due to differences in chemical reactivities. Regardless, living polymerization techniques yielded polymer products that could be useful for surface modifications in biologically implantable devices.;Since protected amino acid NCAs were used to prevent side chain reactions, it was first necessary to deprotect the side chains of the paas to expose the thiol groups for polymer application to gold surfaces. Typically, selective deprotection is desired when heteropolymers are synthesized, but a single deprotection was desired for this study. Successful removals of trifluoroacetyl, carboxybenzyl, and benzyl protective groups were achieved utilizing K 2CO2, and H2O, and MeOH. Removal of the protecting groups was monitored by ¹H NMR and showed that successful global deprotection could be achieved in short order.;Finally, the deprotected poly(amino acid)s were non-specifically deposited onto uniformly coated gold on silica surfaces, as well as, sputtered and nano particulate gold on silica surfaces. PEGylated random and block copolymers were observed on the surfaces utilizing atomic force microscopy (AFM), which showed that the solid gold surface was uniformly covered with PEGylated polymer that yielded characteristic lamellar formation. The gold nano-particle showed a less uniform coating, and demonstrated that PEG could bind to the silica regions in addition to the thiol-gold interactions that were seen in the gold coated surfaces. The gold coated surfaces showed PEGylated polymers were bound only to regions where gold was present. AFM images of gold sputtered silica showed interesting topography, as the PEGylated polymers appeared to yield some spiral like formation on the gold nano particle surfaces, which is commonly termed screw formation. The gold sputtered surfaces showed that cysteine NCA could be incorporated into the copolymer to efficiently provide an anchor for the PEG chain, which could render the surface biocompatible. (Abstract shortened by UMI.)...