Well-defined heterobifunctional homopolyethers and amphiphilic block copolyethers containing a variety of functionalities were designed, synthesized, and characterized via GPC and 1H NMR. These have included controlled molecular weight cholesterol-PEO-OH, mono- and trivinylsilyl-PEO-OH, monovinylsilyl-PEO-PPO-OH, monovinylsilyl-PEO-PPO-PEO-OH, maleimide-PEO-OH, stearyl alcohol-PEO-OH, propargyl alcohol-PEO-OH, trivinylsilyl-PPO-OH, trivinylsilyl-PPO-PEO-OH, and benzyl alcohol-initiated poly(allyl glycidyl ether)-OH. The focus of polymers utilized in this study involved the mono- and trivinylsilyl polyethers. The vinylsilyl endgroups on these materials were functionalized with various bifunctional thiols through free radical addition of SH groups across the vinylsilyl double bonds. The resultant end-functional polyethers were adsorbed onto magnetite nanoparticles and the stabilities of the polymer-magnetite complexes were compared as a function of the type of anchoring moiety and the number of anchoring moieties per chain. Anchoring chemistries investigated in this work included carboxylates, alkylammonium ions, and zwitterionic phosphonates. The anchor group-magnetite bond stability was investigated in water and phosphate buffered saline (PBS). Through these studies, the zwitterionic phosphonate group was shown to be a better anchoring group for magnetite than either carboxylate or ammonium ions. Tri-zwitterionic phosphonate anchor groups provided stability of the complexes in PBS for a broad range of polymer loadings. Thus, investigations into the stability of polyether-magnetite complexes in PBS focused on hydrophilic zwitterionic phosphonate-PEO-OH and amphiphilic zwitterionic phosphonate-PPO-b-PEO-OH oligomer coatings on the surface of magnetite. Superparamagnetic magnetite nanoparticles are of interest as potential contrast-enhancement agents for MRI imaging. Thus, transverse NMR relaxivities of these complexes were studied as a function of chemical composition and nanostructure size and compared to commercial contrast agents. The amphiphilic polyether-magnetite nanoparticles were shown to be stable in both aqueous media as well as physiological media and have much higher transverse relaxation values, r2, than those of commercial contrast agents and other materials in the literature. / Ph. D.

Copolymers that contain terminal or pendent functional groups have great potential in the biomedical area due to their biocompatibility and tunable properties.1-3 In this research, two vinyl functional epoxides, vinyldimethylsilylpropyl glycidyl ether (VSiGE) and ethoxy vinyl glycidyl ether (EVGE), were synthesized. These heterobifunctional monomers were polymerizable via the epoxide groups and can be functionalized via thiol-ene reactions through the pendent vinyl groups. A series of amphiphilic block copolyethers based on poly(ethylene oxide) and poly(1,2-butylene oxide) that incorporate VSiGE or EVGE were synthesized and characterized. The vinyl ether and vinyl silane functional groups were functionalized after polymerization and the functional polymers formed pH-sensitive micelles in aqueous medium. The copolyethers were loaded with ritonavir yielding well-controlled nanoparticles. Poly(L-glutamic acid) is comprised of naturally occurring L-glutamic acid repeating units that are linked together with amide bonds. In this research, we have prepared magnetic block ionomer complexes based on poly(ethylene oxide)-b-poly(L-glutamic acid) copolymers. This is of interest due to the biocompatibility and biodegradable nature of the poly(L-glutamic acid) component of the backbone. Allyl- and thiol-functional poly(ethylene oxide)-b-poly(L-glutamic acid) copolymers were also synthesized and coated onto the surface of iron oxide nanoparticles. Allyl- and thiol-tipped single particles were reacted with each other to prepare magnetic clusters. Transverse relaxivities of the clusters were found to be significantly higher than that of single particles. One major problem in commercial development of therapeutic proteins is their poor transport across cellular membranes and biological barriers such as the blood-brain barrier (BBB). One solution to this problem is to modify proteins with amphiphilic block copolymers such as PEO-b-PPO-b-PEO, Pluronics®. However, it isn't possible to independently tune the two PEO block lengths with commercial Pluronics® since a difunctional PPO macroinitator is utilized to grow both PEO blocks simultaneously (HO-EOn-b-POm-b-EOn-OH). Another challenge is introducing functional group which allows post-polymerization functionalization for specific applications. In this study, a series of heterobifunctional asymmetric amino-EOn1-b-POm-b-EOn2-OH block copolymers (APs) with different molecular weights of each block were synthesized and the amino terminal group was conjugated to an antioxidant enzyme, Cu/Zn superoxide dismutase (SOD1). The conjugates were characterized and their cellular uptake was investigated. / Ph. D.