Synthesis of 2,2-dipyridylamine organometallic complexes for antiplasmodial application
Date
2021-03
Authors
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Journal ISSN
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Publisher
Stellenbosch : Stellenbosch University
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.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar
Description
Thesis (MSc)--Stellenbosch University, 2021.
Keywords
Crystallization, Organometallic chemistry, Organometallic compounds, Solution (Chemistry), UCTD