Design of novel copper(II) based anti-inflammatory drugs for the elevation associated with Rheumatoid Arthritis
Master Thesis
2009
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University of Cape Town
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Abstract
It has been shown that copper complexes are able to alleviate inflammation associated with Rheumatoid Arthritis (RA). Serum copper levels are elevated in RA and it has been postulated that endogenous copper might have a protective function in chronic inflammatory conditions. In designing Cu(I1) anti-inflammatory drugs, one needs to know the stability constants of the ligand together with Cu(I1) and the competitive metal ions, Zn(I1) and Ca(I1) in blood plasma. For this purpose glass electrode potentiometry, infrared (lR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, UV/Visible spectroscopy as well as blood plasma modelling were used to explore the coordination chemistry of a newly designed ligand, PCUL (Bis-(3- aminoethy-2-aminomethylpyridine )-oxahexacyclo-dodecane). PCUL protonation and formation constants with Cu(I1) and Zn(I1) were investigated by potentiometric analysis at 2SoC and 0.ISmol/dm3 Na + (CI) The potentiometric analysis showed that CU(I1) formed far more stable complexes at physiological pH with PCUL than the in vivo competitor Zn(I1). In this study the IR spectroscopic analysis was used to determine the Cu(I1)-PCUL complexation sequence. The IR spectra show that the central amines are coordinated to the metal ion first. The small frequency shift between pH 4.02 to 6.91 proves that the pyridyl nitrogen atoms are also coordinated to CU(I1).
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Mhlambiso, Z. 2009. Design of novel copper(II) based anti-inflammatory drugs for the elevation associated with Rheumatoid Arthritis. University of Cape Town.