Synthesis of mixed ligand, water soluble square planar platinum (II) complexes and an investigation of their association with haematin and potential to inhibit the formation of synthetic malaria pigment

• Main Author: Swan, Paul Lombard
• Other Authors: Egan, Timothy J
• Format: Dissertation
• Language: English
• Published: University of Cape Town 2014
• Subjects: Chemistry
• Online Access: http://hdl.handle.net/11427/9782

Includes bibliography. === To establish their potential as a template for novel anti-malarial drugs, a series of planinum (II) complexes were synthesised, their association with haematin determined in 40 aqueous DMSO, pH 7.4 at 25°C and their ability to inhibit the formation of β-haematin (synthetic malaria pigment) was investigated. The compounds synthesised and investigated contained a platinum (II) ion coordinated to acylthiourea and diimine ligands. The diimines used included both substituted and unsubstituted 2,2’-bipyridines and 1,10-phenanthrolines. 2-phenyl pyridine was also utilised as a ligand. It has been shown that the uncoordinated planar ligands interact weakly with haematin with a log K in the range of 1.9 and 3.3 while the twisted or more sterically hindered ligands show no observable association with porphyrin. A series of complexes having platinum coordinated which was reflected in association constant log K values in the range of 4.8 to 5.8. Using a 1,10-phenanthroline ligand in place of a 2,2-bipyridine ligand increased the association constant of the platinum complex, resulting in this series of complexes having log K values in the range of 5.8 to 6.2. It has been shown that when platinum (II) is coordinated to diimines, it is the electron withdrawing properties of the metal which result in the strong association between the diimine containing complex and haematin. Finally both the complex containing platinum cis to two acylthiourea ligands as well as a platinum complex containing 2-phenyl pyridine were shown to have no observable interaction with haematin.