Supramolecular Self-Assembly: Models for Speciation in Solution and
Ion Channels in Lipid Bilayer Membranes
by
Christine Chia Lin Tong
B.Sc., University of Waterloo, 2000
A Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of
Doctor of Philosophy
in the Department of Chemistry
Abstract:
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 (logβpbh) 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 (logβ’pbh) and a statistical factor (logY). Values for logβ’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 1bromohexadecane 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 long 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 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.