Recognition, Reactivity and Transport with Biomimetic Zinc Complexes

This thesis describes the activity of a range of oxime-Zn2+ complexes as catalysts in solution and in bilayer membranes to develop greater insights into the parameters that will allow the development of more effective transducers in artificial signal transduction systems. This is followed by studies where a membrane-embedded thiol is used to try and activate an inhibited enzyme to exploit the greater efficiency of biological catalysts. Chapter one describes key terms in the bilayer membrane field and describes the research that have been achieved in making supramolecular systems that can transfer information across a bilayer membrane. Chapter two presents the design and the investigation of Zn2+ complexes of small ligands containing oxime moieties. The ability of the complexes to catalyse the hydrolysis of two different ester substrates in solution under physiological conditions has been studied using UV-Visible spectroscopy. The stability of the complexes, the dependence of the activity on both ligand and Zn2+ ion concentration was determined. The findings showed the underlying characteristics of these complexes to allow comparison with the activity of analogues that can be used as part of a membrane signalling. Chapter three focuses on using the ligands which were designed and studied in chapter two as headgroups that were attached to cholesterol and lithocholic acid as a lipophilic moiety. These compounds allowed the investigation of the effect of varying the linker between the hydrophilic and lipophilic moieties, and of the effect of the membrane interface, on the characteristics of the complexes. Moreover, the system used in this chapter is compared to the previously reported membrane transducers. In this chapter, we sought to control the reactivity of this metallovesicullar system and enhance the catalytic efficiency of the reaction. Chapter four aims to see if a molecule containing a thiol group that is anchored in a lipid bilayer membrane (in the form of a vesicle) could be utilised to activate an inhibited enzyme in the aqueous phase and whether the enzyme was capable of amplifying a signal once activated. The second aim was to study whether this would provide a system with the ability to be completely inactive in an ‘off’ state so that it could be used in a membrane translocation system for signal transduction. The final aim was to see if a transducer molecule with a polar headgroup could be made, which could hold the enzyme-activating moiety held inside the vesicle membrane until a primary signal was inputted. Chapter five presents the experimental procedures which used to obtain the synthetic compounds with the yield and characterisation data (NMR, Mass Spectra, IR and HPLC traces).