Date of Award

Fall 12-2008

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Polymers and High Performance Materials

Committee Chair

Dr. Sarah Morgan

Committee Chair Department

Polymers and High Performance Materials

Committee Member 2

Dr. Charles McCormick

Committee Member 2 Department

Polymers and High Performance Materials

Committee Member 3

Dr. Marek W. Urban

Committee Member 3 Department

Polymers and High Performance Materials

Committee Member 4

Dr. James Rawlins

Committee Member 4 Department

Polymers and High Performance Materials

Committee Member 5

Dr. Sabine Heinhorst

Committee Member 5 Department

Chemistry and Biochemistry

Abstract

The primary theme of this dissertation involves the synthesis of well-defined primary amine functionalized polymers, subsequent modification of the polymers to produce novel carboxylic acid functionalized glycopolymers and surface polymerization of these systems utilizing controlled polymerization techniques. Additionally, the synthesis of new water-based allylic copolymer latexes is described. Carbohydrates are natural polymers which possess unlimited structural variations. They carry a huge density of information, and play major roles in recognition events and complex biological operations. For example, hyaluronic acid (HA), an anionic glycosaminoglycan, provides lubricating and cushioning properties in the extracellular matrix and has been found to be involved in the regulation of many cellular and biological processes. In industry, HA is used in a wide range of biomedical applications, including post surgical adhesion prevention, rheology modification in orthopedics, ophthalmic procedures, tissue engineering, hydrogels and implants. Limitations of current systems include cost, allergy induction and reduced performance capabilities in comparison to native HA. Therefore, it is of interest to prepare synthetic glycopolymer analogues to specifically target performance capabilities for biomedical applications.

Reversible addition-fragmentation chain transfer polymerization (RAFT) is arguably the most versatile living radical polymerization technique in terms of the reaction conditions and monomer selection. Since the introduction of RAFT in 1998, researchers have employed the RAFT process to synthesize a wide range of water soluble (co)polymers with predetermined molecular weights, low polydispersities, and advanced architectures. However the RAFT polymerization of primary amine containing monomers such as 2-(aminoethyl metharylate) (AEMA) and ./V-(3-aminopropyl methacrylamide) (APMA) directly in water has yet to be reported. Since primary amine groups are amenable to a wide range of post-polymerization chemistries, primary amine functionalized polymers enable developments in the synthesis of controlled architecture glycopolymers. In addition, "click" chemistry can provide us an easy route to modify solid substrates with these polymers due to its simple reaction conditions and high reaction yield properties. The overall goal of this research is to prepare well-defined synthetic anionic glycosaminoglycan polymers by combining well-defined primary amine functionalized polymers with carboxylic acid functionalized sugars through a one-step reductive amination reaction. To achieve these goals, first, primary amine functionalized polymers were prepared through aqueous RAFT polymerization of AEMA and APMA. Second, Dglucuronic acid sodium salt was attached to reactive polymer precursors via reductive amination reactions in alkaline medium. Finally, the surface modification capabilities of primary amine functionalized polymers were investigated using "click" chemistry to create reactive surfaces allowing post-polymerization reactions.

In this thesis, the first chapter concerns the first successful RAFT polymerization of unprotected AEMA directly in water and its successful block copolymerization with iV-2-hydroxypropylmethacrylamide (HPMA). The controlled "living" polymerization of AEMA was carried out directly in aqueous buffer using 4-cyanopentanoic acid dithiobenzoate (CTP) as the chain transfer agent (CTA), and 2,2'-Azobis(2- imidazolinylpropane) dihydrochloride (VA-044) as the initiator at 50 °C. The living character of the polymerization was verified with pseudo first order kinetic plots, a linear increase of the molecular weight with conversion, and low polydispersities (PDIs) (<1.2). In addition, well-defined copolymers of poly(2aminoethyl methacrylate-6-./V-2- hydroxypropylmethacrylamide) (PAEMA-6-PHPMA) have been prepared through chain extension of poly(2-aminoethyl methacrylate) (PAEMA) macroCTA with HPMA in water. It is shown that the macroCTA can be extended in a controlled fashion resulting in near monodisperse block copolymers. The second chapter demonstrates the synthesis of novel carboxylic acid functionalized glycopolymers prepared via one step post-polymerization modification of poly(JV-[3-aminopropyl] methacrylamide) (PAPMA), a water soluble primary amine methacrylamide, in aqueous medium. PAPMA was first polymerized via aqueous RAFT polymerization using CTP as CTA, and 4,4'-Azobis(4-cyanovaleric acid) (V-501) as the initiator at 70 °C. The resulting well-defined PAPMA was then conjugated with Dglucuronic acid sodium salt through reductive amination in alkaline medium (pH 8.5) at 45 °C. The successful bioconjugation was proven through proton (^H) and carbon (13C) Nuclear Magnetic Resonance (NMR) spectroscopy and Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) mass spectroscopy analysis, which indicated near quantitative conversion. A similar bioconjugation reaction was conducted with PAEMA and PAEMA-6-PHPMA. For the PAEMA homo and block copolymers, however, poor conversion was obtained, most likely due to degradation reactions of PAEMA in alkaline medium. The third chapter details the direct preparation of a-alkynyl-functionalized PAEMA via RAFT polymerization. The controlled "living" polymerization of AEMA was carried out directly in dimethylsulfoxide (DMSO) using a-alkynyl functionalized CTP as CTA, and 2,2'-azobis(2,4-dimethyl-4-methoxyvaleronitrile) (V-70) as the initiator at 45 °C. The resulting polymers display low PDIs (<1.2). In addition, the a-alkynylfuntionalized PAEMA was attached to an azide functionalized silicon wafer via "click" chemistry. Various characterization techniques including ellipsometry, contact angle measurements, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-IR), and atomic force microscopy (AFM) were used to characterize the polymer modified silicon wafers. It was shown that a non-uniform surface with a thickness of 11.1 nm was obtained. The last chapter (an additional chapter) details the copolymerization behavior of styrene with sec-butenyl acetate, whose copolymerization properties have not been reported. Copolymers were produced via semicontinuous emulsion polymerization and characterized via NMR, gel permeation chromatography, differential scanning calorimetry, dynamic light scattering, and atomic force microscopy. A high degree of chain termination due to allylic hydrogen abstraction was observed, as expected, with resultant decreases in molecular weight and in monomer conversion. How percentages of the ever, high conversions were achieved, and it was possible to incorporate high allylic acetate comonomer into the polymer chain. Copolymer thermal properties are reported.

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