The synthesis and electrochemical studies of a new valinomycin analogue containing remote functionality

The natural antibiotic valinomycin is of great interest due to the high complexation selectivity it displays towards potassium ions. This thesis discusses the structure and conformation of the cyclodepsipeptide valinomycin and its cation complexes. The cation binding of a range of synthetic analogues of valinomycin is also reviewed. The analytical and biomedical applications of valinomycin and its use in the development of potassium sensors are discussed and some current problems highlighted. The syntheses of cyclodepsipeptides are discussed. A valinomycin analogue cyclo[(D.Phe.Hyiv.Phe.D.Lac)2D.Phe.Hyiv.Tyr.D.Lac] which contained a remote phenolic hydroxyl group was synthesised. The phenolic hydroxyl of the tyrosine residue was successfully protected as the acetate throughout the synthesis. The spectral characteristics of the new cyclodensipeptide were investigated and found to be very similar to those of the natural antibiotic valinomycin. The metal complexation of the new cyclodepsipeptide was studied with NMR and using a range of electrochemical techniques. The cation selectivity S and complex stability Ks of some cation complexes of the new depsipeptide were evaluated using cyclic voltammetry studies at the interface between two immiscible electrolytic solutions. The new depsipeptide displayed the same cation selectivity asw that of valinomycin, but it was found that the complex stability Ks (in dichloroethane) was lower than that of valinomycin by a factor of ten. The heterogeneous rate constant for the potassium complex formation Kf of the new depsipeptide, valinomycin and two cyclodepsipeptides previously synthesised in this laboratory were determined from potential step chronocoulometry experiments. The importance of the extension of this methodology to the determination of the heterogeneous rate constant of valinomycin and its analogue is noted. A comparison is made between the heterogeneous and homogeneous rate constants of valinomycin complexation. The attachment of the new depsipeptide to an electrode surface by the covalent bonding of the remote funtionality is also briefly discussed.