Repository logo

Competitive interactions between copper(II) ions, thiomolybdates, and some biological ligands



Journal Title

Journal ISSN

Volume Title




Degree Level



Thiomolybdates formed in the rumen have been implicated in copper deficiency in ruminants. However, the chemical basis of the interaction between the individual thiomolybdates and both dietary and systemic copper is poorly understood. Which particular thiomolybdate(s) are formed in the rumen has also been an issue of contention. In part, these problems can be ascribed to lack of availability of synthesized thiomolybdates of known purity. The main objective of this study was to determine the chemical mechanism by which thiomolybdates render Cu(II) unavailable for utilization in ruminants, particularly cattle. In the thesis, facile methods are described for the preparation of ammonium dithiomolybdate and tetrathiomolybdate, and of cesium monothiomolybdate and trithiomolybdate. The methods involve successive replacement of the oxygen atoms in sodium molybdate by sulfur atoms using ammonium sulfide. This is the first time the cesium salt of the monothiomolybdate has been reported in pure form. Previous studies in the literature have assumed purity of the thiomolybdates based on elemental analysis; this is not sufficiently discriminating. A more thorough analysis, based on multi-wavelength analyses of the UV/visible spectra of the products, and of mixtures, was used to determine the actual purity of these samples. Discrepancies in previously published spectra for these materials can now be ascribed to unrecognized variations in purity. It is also possible to judge the performance of previously published purification methods of these materials. The relative proportions of the different thiomolybdates formed under conditions simulating those within the rumen fluid of ruminants prone to copper deficiency have been measured from UV/visible spectra data. Pure synthesized thiomolybdates have also been used to study spectrophotometrically the interactions between the thiomolybdates and Cu(II) in the presence and absence of some inorganic ligands, low molecular mass complexing agents and bovine serum albumin, in aqueous solutions. Some small peptides (His-Lys, Thr(Ac)-His-Lys and Asp-Thr(Ac)-His-Lys) were synthesized and characterized and employed as models to study the influence of bovine serum albumin, the main protein for transporting "exchangeable" copper in the blood plasma, on the Cu(II)-thiomolybdate interactions. 1H NMR was used to study the acid-base behaviour of these peptides and their complexation with Cu(II) in H20. Changes in the chemical shifts of these peptides were obtained as a function of pH and from these, reliable Ka values have been established. Probable binding sites of Cu(II) and the relative strengths of binding to these peptides are also discussed. To investigate the possible 3-way interaction between bovine serum albumin, Cu(II) and thiomolybdates, both 1H NMR and UV/visible spectroscopy were used to study the ternary complexation between the peptide models, Cu(II) and thiomolybdates. The results show clearly that ternary complexes, which are poorly soluble in water, are formed between these three species. It was not possible to come to a definite conclusion about the structure of the ternary complex. However, results seem to suggest a core unit where the peptide binds Cu in the +1 state via the terminal amino N, the imidazole N-3 nitrogen and two sulfur atoms from the thiomolybdate. Polymerization of this core unit seems to occur, especially for the interaction involving the tetrathiomolybdate. Throughout the studies it was noted that tetrathiomolybdate behaved differently from the other thiomolybdates in several respects: stability in aqueous solutions; the kinetics of the interactions with Cu(II); the stability of the resulting products from the interaction with copper(II); the formation of insoluble products and/or polymerization of the core units of the ternary complex initially formed.





Doctor of Philosophy (Ph.D.)




Part Of