| The research described in this thesis focuses on characterization of the interactions between a redox-active ferrocenyl amphiphile, (11-ferrocenylundecyl)dimethylammonium bromide (BFDMA), and nucleic acids (DNA) using a range of physicochemical techniques. It is motivated by a previous observation that, whereas multilamellar aggregates of reduced BFDMA and DNA (lipoplexes) transfect cells with high efficiency, amorphous lipoplexes of electrochemically oxidized BFDMA and DNA lead to low levels of transfection. Therefore, BFDMA provides a novel redox-based approach to the mediation of cell transfection.;The results presented herein move beyond this observation using cell transfection assays in combination with small angle x-ray and neutron scattering and cryo-TEM analysis to demonstrate and characterize the ability of BFDMA to spontaneously aggregate with dioleoylphosphatidylethanolamine (DOPE) and DNA forming serum-stable, inverse hexagonal nanostructured, lipoplexes able to mediate the delivery of DNA to mammalian cells in vitro in media containing physiologically relevant levels of serum.;A second study reported in this thesis demonstrates the ability of BFDMA to be chemically oxidized using Fe(III)sulfate in the presence of DNA. When excess Fe ions are chelated using EDTA, the lipoplexes of oxidized BFDMA and DNA do not transfect cells with high efficiency. However, when the chemical reducing agent, ascorbic acid is used, the efficiency of cell transfection increased substantially, demonstrating chemical control of the oxidation state and transfection efficiency of lipoplexes of BFDMA and DNA.;Finally, this thesis reports an investigation of how self-assembly impacts the rate of electrochemical oxidation of BFDMA. BFDMA spontaneously adsorbs to Pt disk electrodes, forming an absorbed layer blocking the electrode from exchanging electrons with BFDMA diffusing in bulk solution. In contrast, (11-ferrocenylundecyl)trimethylammonium bromide (FTMA), a similarly Pt electrode adsorbing ferrocenyl amphiphile, allows exchange of electrons with species in bulk solution across the adsorbed layer. Differential scanning calorimetry and dynamic light scattering results combined to show that the phase state, not the aggregate size, dominates the interfacial electrochemical activity of these amphiphilic redox-mediators.;The in vitro based studies and insight obtained from supporting physicochemical characterization presented herein provide important steps toward the development of redox-active lipid materials that permit spatial and/or temporal control over cell transfection. |
