Synthesis of 2,2-dipyridylamine organometallic complexes for antiplasmodial application
| dc.contributor.advisor | Prinessa, Chellan | en_ZA |
| dc.contributor.author | Manye, Remofilwe | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science. | en_ZA |
| dc.date.accessioned | 2021-05-24T07:36:39Z | |
| dc.date.available | 2021-05-24T07:36:39Z | |
| dc.date.issued | 2021-03 | |
| dc.description | Thesis (MSc)--Stellenbosch University, 2021. | en_ZA |
| dc.description.abstract | ENGLISH ABSTRACT: Six iridium, rhodium and ruthenium half-sandwich organometallic complexes (C1-C6) of the ligand 2,2- dipyridilamine with either a chlorido and iodido ancillary ligand were synthesized using a reported method and their biological activity was investigated. C1-C6, complexes bearing a PF6- counterion, have been reported in literature. Single crystal structures of iridium (C1) and rhodium (C2) chlorido complexes were solved and both were found to have crystallised in the orthorhombic P212121 space group. The aqueous solubility of C1-C6 ranged from poor (<10 μg/mL) to good solubility (> 60 μg/mL). The ruthenium-iodido complex C6 was the least soluble up to 7 μg/mL. Hydrolysis studies were conducted, and it was found that chlorido complexes C1, C5 and C6 did not undergo hydrolysis. The chlorido complexes C2 and C3 did undergo hydrolysis, however, complete displacement of the chlorido with deuterium oxide did not occur. Novel complexes C7-C12, analogues of C1-C6 bearing a NO3- counterion were also synthesized using an adapted method of the PF6- complexes. The crystal structures of complexes C7 and C9 were solved. Iridium chlorido complex C7 was found to crystallise in the monoclinic P21/c space group and ruthenium chlorido complex C9 was found to crystallise in the triclinic P-1 space group. Complexes C7, C8, C9, C11 and C12 were found to have good solubility to a maximum concentration of 200 μM. Iridium iodido complex C8 was moderately soluble >41 μg/ml. Hydrolysis studies of complexes C7-C12 showed that chlorido complexes C8 and C9 and iodido complex C12 were hydrolysable. Generally, chlorido complexes for both PF6- and NO3- counterions were relatively easily hydrolysable compared to iodido complexes with the exception of chlorido complex C7 and iodido complex C12. The in vitro biological antiplasmodial activity of the ligand, 2,2-dipyridilamine, and complexes C1-C6 was evaluated against two Plasmodium falciparum strains, complexes C7-C12 were not evaluated due to time constraints. The ligand was found to be inactive up to a concentration of 5mM against 3D7 strain, a chloroquine sensitive strain of Plasmodium falciparum parasite. The complexes showed activity against the 3D7 strain, however, the complexes were not as active as currently used antimalarial drugs. Rhodium complexes C2 (IC50 = 4.72 μM) and C5 (IC50 = 5.76 μM) were the most active and iridium chlorido complex C1 (IC50 = 8.93 μM) was the least active amongst complexes C1- C6. Activity of the chlorido versus iodido complexes of iridium and rhodium were presumed to be associated with their relative solubility in aqueous based medium, the more soluble complexes were more active. This argument was not applicable for the ruthenium complexes, the less soluble complex C12 (IC50 = 7.91 μM) showed better activity than the more soluble complex C6 (IC50 = 7.57 μM). The ligand and complexes showed no activity against chloroquine sensitive NF54 strain in a two- and three- day assay. The inactivity may be related to the use of hypoxanthine in the growth media which could be countering the compounds’ mode of action resulting in a delayed response time. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar | af_ZA |
| dc.description.version | Masters | en_ZA |
| dc.format.extent | 71 pages | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/110481 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject | Crystallization | en_ZA |
| dc.subject | Organometallic chemistry | en_ZA |
| dc.subject | Organometallic compounds | en_ZA |
| dc.subject | Solution (Chemistry) | en_ZA |
| dc.subject | UCTD | en_ZA |
| dc.title | Synthesis of 2,2-dipyridylamine organometallic complexes for antiplasmodial application | en_ZA |
| dc.type | Thesis | en_ZA |