Abstract
Metallothionein complexes are of a complex nature and have yet to be fully characterised. The work in this thesis concentrates on the complexation of oligopeptide fractions similar to those in thionein with cadmium (II) so as to simulate the complexation sites in the protein and to help clarify the most likely points of attachment of the metal. Complexes of related ligands have also been investigated. In Chapters 2-5 the preparation of various types of ligands, their complexes with cadmium (II) and the solution behaviour of these complexes are described. Cadmium (II) forms octahedral and pseudoctahedral complexes of the type CdL2X2 or CdLX2 (X = halide) with non-thiol ligands such as pyridine, diaminodithiaoctane, 1,3-bis-(2-aminoethyl)-1,3-propanediamine, the Schiff's base 2-hydroxyacetophenoneethylenediimine, and dioxocyclam. In these complexes the ligand complexation sites are N or/and O atoms with the halides acting as bridging ligands. Ligands which contain thioether donor sites only, e.g. tetrathiadioxatricyclohexacosane, do not form complexes with cadmium (II), but if another coordinating group is present in the same ligand, e.g. NH2 or COOH, complexes are readily formed with likely involvement of the thioether group in coordination. Hence the complexes CdL2 and CdLCl were obtained with S-benzyl-L-cysteine and S-benzyl-L-cysteine ethyl ester respectively. Monocarboxylate monothiol ligands, e.g. cysteine and 2-thiolethanoic acid, form the complexes [Cd(HL)X]n in ethanol and [CdL]n in water in which X = halide, thiolate groups or carboxylate groups act as bridging ligands. In case of dithiolate ligands such as 1,2-ethanedithiol, 1,3-propanedithiol, trans-1,2-dithiolcyclohexane and 1,4,8,11-tetrathiaunedecane polynuclear complexes form in which all the S atoms complex to one metal and some are also involved in bridging. Biological thiol ligands such as L-cysteine and D-penicillamine also form polymeric type complexes with cadmium (II) of formulae [Cd(HL)X]n and [Cd(L)]n. A number of peptide complexes of cadmium (II) have been isolated. These include [Cd(H2L)Cl]n and [Cd3L2]n where H3L is glutathione; Cd2(HL)Cl3 and Cd2LCl2 where H2L is gly-cys; Cd2(HL)Cl2 and Cd(L)Cl where H3L is cys-cys; and CdL.xH20 where H2L is gly-cys-gly, gly-cys-ala, gly-cys-val, leu-cys-leu and val-cys-val-val. Dissociation and complex formation equilibria involving a number of cysteine-containing tri- and tetra-peptide ligands were investigated by potentiometric methods and the data analysed using the "MINIQUAD" computer program. The ligands investigated were gly-cys-AA (AA = gly, ala, val), val-cys-val, thr-cys-val, asp-cys-val, leu-cys-leu, val-val-cys-val and val-cys-val-val (their synthesis is described in Chapter 4). At ligand to metal ratios of 1:1 the main complex species in solution are LMH (111), LM (110) and LMOH (11-1) the last of these being formed as a result of deprotonation of an aquo ligand. Peptide ligands containing a thiolate and two carboxyl groups such as asp-cys-val form higher stability constants than those with no thiolate or carboxyl group such as gly- gly-gly or those with a thiolate group but without a side chain carboxylate such as val-cys-val. This indicates that stronger complexes between Cd(II) and cysteinyl peptides will be formed when a coordinating group such as CO2 is present in the ligand side chain. The major coordinating sites are therefore most probably the thiolate, carboxyl and terminal amino (when available) groups. Likely structures for the complexes formed in solution are proposed.