The membrane is a key component of cells as it acts as a barrier with the extracellular matrix, preventing alien entities from entering the cell unhindered. It also
provides the medium for membrane embedded proteins to bind and react to small molecule messengers and with other cells. The research described in this thesis is focused on the study of the thiol-disulfide reaction at the membrane interfaces in order to understand how this environment affects reactivity and mechanism relative to aqueous solution. This knowledge informs the design of artificial biomimetic systems based on vesicles, which have long been used as the cell membrane model of choice.
Firstly the stability and reactivity of the different thiols and disulfides as well as a water soluble phosphine and potassium ferricyanide were studied in solution. The observed rates for thiol-disulfides exchange reactions in solution were shown to increase with decreasing thiol pATa. A wide range of reactivity and mechanistic pathways were established.
Thiol-disulfide exchange reactions were then studied at the vesicle interface, with one of the two reactants confined to the vesicle membrane. Conditions were
created to study potential intravesicular reaction as well. The membrane interface did not significantly alter the rates of the reactions studied. Studies between embedded molecules suggested that the reaction was not rapid under the conditions used, which is consistent with earlier studies. However, exchange of embedded molecules between interior and exterior surfaces appears to occur which has implications for the utility of these systems.
When reactive components were placed in separate vesicles, rapid changes were observed. These were principally due to electrostatic interactions, generating large aggregates. These aggregates did not appear to be greatly stabilized when covalent connections could also be made.