Novel imidazole-containing polyelectrolytes based on poly(1-vinylimidazole) (poly(1VIM)) were functionalized with various hydroxyalkyl-substituents to investigate the influence of charge density and hydrogen bonding on nonviral DNA delivery. Copolymers with higher charge densities exhibited increased cytotoxicity, whereas increased hydroxyl concentrations remained nontoxic. DNA binding affinity increased with increased charge densities and increased hydroxyl content. Dynamic light scattering determined the copolymers which delivered DNA most effectively maintained an intermediate binding affinity between copolymer and DNA. Copolymers containing higher charge densities or hydroxyl concentrations bound DNA too tightly, preventing its release inside the cell. Copolymers with lower charge densities failed to protect the DNA from enzymatic degradation. Tuning hydrogen bonding concentration allowed for a less toxic and more effective alternative to conventional, highly charged polymers for the development of nonviral DNA delivery vehicles. The synthesis of amine-containing imidazolium copolymers functionalized with low concentrations of folic acid enabled the investigation of additional polymer modifications on nonviral gene delivery.
Functionalization of 1VIM with various hydroxyalkyl and alkyl groups and subsequent conventional free radical polymerization afforded a series of imidazolium-containing polyelectrolytes. Hydroxyl-containing homopolymers exhibited higher thermal stabilities and lower T<sub>g</sub>'s compared to the respective alkyl-analog. X-ray scattering demonstrated the polarity of the hydroxyl group facilitated solvation of the electrostatic interactions disrupting the nanophase-separated morphology observed in the alkylated systems. Impedance spectroscopy determined hydroxyl-containing imidazolium homopolymers displayed higher ionic conductivities compared to the alkyl-containing analogs which was attributed to increased solvation of electrostatic interactions in the hydroxyl analogs.
Beyond functionalizing 1VIM monomers and homopolymers to tailor various properties, the synthesis of novel architectures in a controlled fashion remains difficult due to the radically unstable N-vinyl propagating radical. The regioisomer 4-vinylimidazole (4VIM) contains two resonance structures affording increased radical stability of the propagating radical. Nitroxide-mediated polymerization (NMP) and atom transfer radical polymerization (ATRP) failed to control 4VIM homopolymerizations; however, reversible addition-fragmentation chain transfer (RAFT) demonstrated unprecedented control. Linear pseudo-first order kinetics were observed and successful chain extension with additional 4VIM suggested preservation of the trithiocarbonate functionality.
Effectively controlling the polymerization of 4VIM enabled the design of amphoteric block copolymers for emerging applications. The design of ABA triblock copolymers with 4VIM as a high T<sub>g</sub> supporting outer block and di(ethylene glycol) methyl ether methacrylate (DEGMEMA) as a low T<sub>g</sub>, inner block, required the development of a new difunctional RAFT chain transfer agent (CTA). The difunctional CTA successfully mediated the synthesis of the ABA triblock copolymer, poly(4VIM-b-DEGMEMA-b-4VIM), which exhibited microphase separated morphologies. The amphoteric nature of the imidazole ring required substantially lower concentrations of outer block incorporation compared to traditional triblock copolymers to achieve similar mechanical properties and microphase separated morphologies. / Ph. D.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/49593 |
| Date | 07 January 2013 |
| Creators | Allen, Michael H. Jr. |
| Contributors | Chemistry, Long, Timothy E., Grove, Tijana, Moore, Robert Bowen, Edgar, Kevin J. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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