Synthesis And Applications Of Ring Opening Metathesis Polymerization Based Functional Block Copolymers (2010)

Ring opening metathesis polymerization (ROMP) is established as one of the efficient controlled living polymerization methods which have various applications in polymer science and technology fields. The research presented in this dissertation addresses several applications of multifunctional well-defined norbornene-based block copolymers synthesized by ROMP using ruthenium-based Grubbs catalysts. These novel block copolymers were applied to stabilize maghemite nanoparticles, creating the superparamagnetic polymeric nanocomposites. The Jaggregation properties of the porphyrin dyes were improved via self-assembly with a customized norbornene polymer. Novel multimodal copolymer probes were synthesized for two-photon fluorescence integrin-targeted bioimaging. In Chapter 1 a brief overview of ROMP along with ruthenium metal catalysts and selected applications of the polymers related to this research is presented. Superparamagnetic maghemite nanoparticles are important in biotechnology fields, such as enhanced magnetic resonance imaging (MRI), magnetically controlled drug delivery, and biomimetics. However, cluster formation and eventual loss of nano-dimensions is a major obstacle for these materials. Chapter 2 presents a solution to this problem through nanoparticles stabiulized in a polymer matrix. The synthesis and chracterization of novel diblock copolymers, consisting of epoxy pendant anchoring groups to chelate maghemite nanoparticles and steric stabilizing groups, as well as generation of nanocomposites and their characterization, including surface morphologies and iv magnetic properties, is discussed in Chapter 2. In Chapter 3, further improvement of the nanocomposites by ligand modification and the synthesis of pyrazole-templated diblock copolymers and their impact to stabilize the maghemite nanocomposite are presented. Additionally, the organic soluble magnetic nanocomposites with high magnetizations were encapsulated in an amphiphilic copolymer and dispersed in water to assess their water stability by TEM. To gain a preliminary measure of biocopatibility of the micelle-encapsulated polymeric magnetic nanocomposites, cell-viability was determined. In Chapter 4, aggregation behaviors of two porphyrin-based dyes were investigated. A new amphiphilic homopolymer containing secondary amine moieties was synthesized and characterized. In low pH, the polymer became water soluble and initiated the stable Jaggregation of the porphyrin. Spectroscopic data supported the aggregation behavior. Two photon fluorescence microscopy (2PFM) has become a powerful technique in bioimaging for non-invasive imaging and potential diagnosis and treatment of a number of diseases via excitation in the near-infrared (NIR) region. The fluorescence emission upon two-photon absorption (2PA) is quadratically dependent with the intensity of excitation light (compared to the linear dependence in the case of one-photon absoprtion), offering several advantages for biological applications over the conventional one-photon absorption (1PA) due to the high 3D spatial resolution that is confined near the focal point along with less photodamage and interference from the biological tissues at longer wavelength (~700-900 nm). Hence, efficient 2PA absorbing fluorophores conjugated with specific targeting moieties provides an even better bioimaging probe to diagnose desired cellular processes or areas of interest The αVβ3 integrin v adhesive protein plays a significant role in regulating angiogenesis and is over-expressed in uncontrolled neovascularization during tumor growth, invasion, and metastasis. Cyclic-RGD peptides are well-known antagonists of αVβ3 integrin which suppress the angiogenesis process, thus preventing tumor growth. In Chapter 5 the synthesis, photophysical studies and bioimaging is reported for a versatile norbornene-based block copolymer multifunctional scaffold containing biocompatible (PEG), two-photon fluorescent (fluorenyl), and targeting (cyclic RGD peptide) moieties. This water-soluble polymeric multi scaffold probe with negligible cytotoxicity exhibited much stronger fluorescence and high localization in U87MG cells (that overexpress integrin) compared to control MCF7 cells. The norbornene-based polymers and copolymers have quite remarkable versatility for the creation of advanced functional magnetic, photonic, and biophotonic materials.