Metal ion equilibria in biofluids - copper and rheumatoid arthritis

Doctoral Thesis

1998

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University of Cape Town

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A computer model of blood plasma has been used to evaluate the factors affecting the ability of a ligand to increase the low molecular weight copper pool in vivo. The justification for using this speciation approach is based on the assumption that the low molecular weight copper complexes are important in the reduction of the inflammation associated with rheumatoid arthritis. Based on the results of the simulation, two novel ligands, 3,6,9, 12-tetra-azatetradecanedioic acid (dtda) and 3,6,9,-triazaundecanedioic acid (dtda) have been synthesised using a three step route. Multiple carboxylation was prevented by using the tosylate protecting group. The compounds were obtained in an overall yield of 14.7 and 29.0 , respectively, and characterised using n.m.r, l.R. and mass spectrometry. The stability constants of the complexes formed by these ligands with several metal-ions were determined using glass electrode potentiometry at 25°C and an ionic strength of 0.15 mol dm3. The metals used were the divalent ions of magnesium, calcium, manganese, cobalt, nickel, copper and zinc. The values determined followed the Irvine-Williams order of stability.
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