Preparation of novel amphiphilic polymers via ring -opening metathesis polymerization and study of their antibacterial properties

This thesis adapted tools of organic and organometallic chemistry to achieve control over synthetic macromolecular architectures, with a focus on the systematic incorporation of polar and nonpolar chemical entities into polymers, and test these amphiphilic polymers for their interactions with living cells, bacterial and mammalian. The development of highly active well-defined catalyst systems for olefin metathesis, and their influence on the development of ring-opening metathesis polymerization (ROMP) has been a major inspiration behind our synthetic strategy towards the preparation of model amphiphilic polymer architectures with a high level of structural control. The first synthetic approach was the investigation of ring-opening metathesis copolymerization of polar and nonpolar cyclic olefins as monomers. This study leads to the discovery of alternating copolymerizations of a series of polar cyclic olefins with nonpolar cyclic olefins using ruthenium-based homogeneous catalyst system. Mechanistic studies revealed that steric factors induced from comonomer structures and catalyst type affect the degree of alternation on the polymer backbone. This novel technique allows for the strictly alternating incorporation of polar and nonpolar monomeric units into polymer chains of various lengths, and facilitates the polymerization of sterically encumbered monomers and modification of final material properties. In a second synthetic approach, a general strategy was developed for the assembly of polar and nonpolar domains into a modular monomer structure. The character and size of each domain can be tuned independently and locked into the repeating unit of the amphiphilic polymers resulting from ROMP of the modular norbornene derivatives. Living ROMP of these monomers provided access to a large range of molecular weights with narrow molecular weight distributions. Lipid membrane disruption activities, a key feature of amphiphilic polymers used in many biomedical applications, were investigated for amphiphilic polynorbornene derivatives against liposomes. Water-soluble amphiphilic cationic polynorbornene derivatives, which exhibited the highest level of activities against liposome membranes, were then probed for their antibacterial activities in growth inhibition assays and hemolytic activities against human red blood cells in order to determine the selectivity of the polymers for bacterial over mammalian cells. By tuning the overall hydrophobicity of the polymer, highly selective, non-hemolytic antibacterial activities were obtained