The self-assembled complex (Pden)4(bipy)4+8 is potentially suited as a portal for synthetic ion channels (Pden = (1, 2-ethylenediamine) Pd(II), bipy = 4, 4'-bipyridine). This thesis examines the solution speciation of mixtures of Pden and bipy and the ion channel activity of the proposed channel. A model which describes the concentration of the species in solution as a function of pH and Pden:bipy ratio was developed. The method determines the solution speciation by solving the mass balance equation for each species using the total concentration of Pden, bipy and H+ and the cumulative formations constants for species in solution. This model is general and can be applied to other systems provided that the cumulative macroscopic formation constants (logßpbh) of the species are either known or can be estimated. The cumulative macroscopic formation constant for a species is determined by an additive free energy process as the sum of the logarithms of a microscopic formation constant (logß'pbh) and a statistical factor (logY). Values for logß'pbh were estimated using stepwise formation constants (logK) for model systems which were determined by potentiometric titration. Values for logY were calculated from the symmetries of the species. The model calculates the concentration of each species as a function of pH and Pden:bipy ratio to give a map of the species and their relative concentrations. The model shows that (Pden)4(bipy)4 is the single most abundant species between pH = 4 and 7 and a Pden:bipy ratio of 1:0.4 to 1:6. Under optimum conditions, (Pden)4(bipy)4 holds a maximum of -80 % of the total Pd in solution when the total [Pd] = 1 x 10-5 M. The apparent equilibrium constants for 2.(Pden)(bipy)2 = (Pden)2(bipy)3+bipy and 4.(Pden)(bipy) = (Pden)4(bipy)4 were -0.6 and --106, respectively, at Pden:bipy = 1:1 and pH = 7. The model also permits analysis of the relative rates of formation of (Pden)4(bipy)4 from a number of different precursors. The dominant stepwise processes for the formation of (Pden)4(bipy)4 are dimerization of (Pden)2(bipy)2, addition of Pden to (Pden)3(bipy)4 and addition of (Pden)2(bipy) to (Pden)2(bipy)3. Other possible pathways to (Pden)4(bipy)4 involve less abundant species so are disfavored. Lipophilic derivatives of Pden (PdenR) were synthesized from 1-bromodecane or 1-bromohexadecane and solketal in 30 % and 23 % overall yield, respectively. The complex PdenR was reacted with bipy in acetonitrile and the resultant solution was then tested for ion channel activity using the bilayer clamp experiment. The decyl derivative (R = C10H21) was inactive but a range of activity which include erratic behaviors, short openings and Iong openings were observed for the hexadecyl derivative (R = C16H33) using the bilayer clamp technique. Erratic openings were observed before all short and long openings, but were also observed independently. Hille pore radii, calculated from the observed conductances, were between ˜ 1 and 6.5 Å for the rare short openings. The Hille radii for long opening pores were between ˜1 and 14 Å and these pores did not show any ion selectivity. Channels that exhibit long opening activity were also observed in the absence of Pden:bipy. The large Hille radii and activity in the absence of bipy indicate that the proposed (PdenR)4(bipy)4 channel did not form possibly because the local concentration of bipy was not high enough to compete with the lipid for coordination sites on PdenR. The implications of these findings for self-assembly of ion channels in lipid bilayer membranes are discussed.

Thesis (Ph.D.) -- McMaster University, 1997 / Includes bibliographical references (leaves 151-167) Also available via World Wide Web.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (p. 128-145).

Thesis (M. Sc.)--Memorial University of Newfoundland, 1998. / Bibliography: leaves 68-75.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 157-167.

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Plasma membranes are essential to both the structure and function of mammalian cells. The first unifying paradigm of membrane structure, the Fluid Mosaic Model, is no longer considered adequate to describe the many non-homogeneous lipid structures that have been observed in both natural and model membranes over the past approximately thirty years. The field of membrane biophysics now appreciates that the complex mixture of different lipid species found in natural membranes produces a range of dynamic, laterally segregated, non-homogeneous structures which exist on time scales ranging from microseconds to minutes. When sphingomyelin (SM), POPC and cholesterol are all present in a bilayer there is wide range of compositional ratios where the bilayer consists of a coexistence between two fluid phases designated liquid ordered (lo) and liquid disordered (ld). The lo phase is cholesterol-rich phase characterized by relatively high molecular order and slow rotational and translational motion, while the ld phase generally has low molecular order and relatively rapid rotational and translational motion. The driving force for the formation of these two phases is the ability of cholesterol to form favorable van der Waals contacts with the two saturated acyl chains on PSM and the one saturated acyl chain on POPC. The ternary system is an important model system for examining the physical properties and functional implications of co-existing lo and ld phases. However, it does not include one of the most significant compositional variables found in many important mammalian membranes. Membranes in the nervous system contain high concentrations of the highly polyunsaturated fatty acid docosahexaenoic acid (DHA), which contains 22 carbons and 6 double bonds. A wide range of experimental evidence shows that DHA-containing phospholipids are important for optimal performance of a number of membrane signaling systems and membrane protein functions. The goal of this study is to determine how addition of a DHA-containing phospholipid, PDPC alters the biologically important lo and ld co-existence region.

In this study we have investigated the frequency dependence of bilayer lipid membranes for a series of glycerylmonoolein/ n-decane bilayers in various aqueous ionic solutions containing the ionophore valinomycin. Reliable values of membrane capacitance and conductance were obtained over the frequency range 0.2 - 200 KHz using an automatic balancing bridge under the control of a microprocessor unit. The admittance data was then normalized and curve-fitted to produce relaxation times and amplitudes from which the kinetic rate parameters, as deduced from a single slab dielectric membrane model, were calculated. These ac experimental rate constants were then compared with those obtained from charge-pulse relaxation methods.

The question of how ions interact with each other and with the potential energy barrier in thin lipid bilayer membranes has interested investigators for several years. The application of electrodiffusion theory to the study of this question is the central theme of this work. We have calculated current-voltage curves for barriers of various shapes and heights, in each case by means of numerically integrating the exact electrodiffusion equation as well as this same equation in the constant field approximation. We have also calculated the total charge in the membrane for the same conditions under which we have calculated the current-voltage curves.