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Furst, Alexandra (1995) An analytical study of the role of selected metal ions in bone and joint diseases. Doctoral thesis, University of North London.
Metal ions play a major role in a wide range of biological processes in the human body. Metal ions in low-molecular weight complexes are of particular interest because of their greater 'mobility' and 'reactivity' compared to the high-molecular weight protein-bound metal ions. In this project, low-molecular weight metal ions encountered in vivo due to bone and joint disease are studied, namely gold, titanium and iron metal ions.
Gold compounds such as disodium aurothiomalate (Myocrisin) have been used for over 50 years in the treatment of rheumatoid arthritis (RA). As gold (I) acts like a soft Lewis acid, it possesses a high affinity for thiol ligands and therefore primarily distributes itself amongst protein and to some extent non-protein thiol groups in vivo. Most of the gold is bound to the protein serum albumin, principally at the sulphydryl site Cys(34)-SH, and a smaller amount is bound to immunoglobulins. A small amount of the total circulating gold is present as low-molecular weight or "free" gold, which is likely to play an important role in gold transportation processes and the attainment of chemical equilibrium of gold between the protein binding sites.
In this study the concentration of low-molecular weight gold in the biological fluids of RA patients undergoing gold drug therapy (chrysotherapy) was analysed. The biological samples were centrifuged in order to obtain ultrafiltrate which would be free of highmolecular weight gold. The ultrafiltrate, containing the low-molecular gold was treated with potassium cyanide to facilitate the production of an auro(I)cyanide complex which could detected and quantified by the use of high pressure liquid chromatography (HPLC) in conjunction with ultra-violet (UV) detection at a wavelength of 211 nm. HPLC provided a method that was sensitive to the low concentrations found. The results obtained were backed up by measuring the "free" gold concentration by means of flameless atomic absorption spectrometry (AAS).
In addition the chemical nature of titanium ions found in localised darkly stained tissue adjacent to titanium-aluminium-vanadium hip implants was investigated. The production of the dark blue/black complex seen in the affected tissue was simulated in vitro by synthetic pathways. The speciation of the titanium (III)/titanium (IV) complexes in the biological matrices was investigated with Fourier transform infra red (FTIR) spectroscopy and high field proton nuclear magnetic resonance (NMR) with a Hahn spin echo pulse sequence.
The chemical nature of non-protein bound iron present in knee joint synovial fluid obtained from RA patients was also investigated by use of NMR
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