Modular Norbornene Derivatives for the Preparation of Well-Defined Amphiphilic Polymers:  Study of the Lipid Membrane Disruption Activities

Novel 2,3-disubstituted-7-alkylidene norborn-2-ene derivatives (1 − 4) were prepared through Diels−Alder cycloaddition of fulvene derivatives and appropriate dienophiles. The ring-opening metathesis polymerization of this type of modular monomer was studied using a molybdenum alkylidene catalyst (7) and three different ruthenium carbene catalysts (8−10). Through the choice of monomer and catalyst it was possible to obtain polymers with a range of molecular weights and narrow polydispersities (1.08−1.20). The resulting polymers were quantitatively transformed to water-soluble amphiphilic polymers through simple chemical modifications. By changing the monomer structure, it was possible to tune the balance of hydrophobicity and ionic nature of the final polymer. The interaction of these polymers with phospholipid membranes was studied using large unilamellar vesicles that entrap a fluorescent dye. To probe the effect of polymer molecular weight, ionic nature, and hydrophobic character on membrane disruption activity, polymer-induced dye leakage from the large unilamellar vesicles was measured.