Supramolecular self-assembly: models for speciation in solution and ion channels in lipid bilayer membranes
Date
2009-12-18T21:58:42Z
Authors
Tong, Christine Chia Lin
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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 (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.
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Keywords
ion channels, bilayer lipid membranes