Quinoline-triazole half-sandwich iridium(iii) complexes : Synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies
(2020) In Dalton Transactions 49(33). p.11543-11555- Abstract
Iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against the Plasmodium falciparum malaria parasite. Supporting computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming a kinetic product that, upon heating over time, forms a more stable cyclometallated thermodynamic product. Single crystal X-ray diffraction confirmed the proposed molecular structures of both isolated kinetic and thermodynamic products. Complexation with iridium significantly enhances the in vitro activity of selected ligands against the chloroquine-sensitive (NF54) Plasmodium falciparum strain, with selected complexes... (More)
Iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against the Plasmodium falciparum malaria parasite. Supporting computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming a kinetic product that, upon heating over time, forms a more stable cyclometallated thermodynamic product. Single crystal X-ray diffraction confirmed the proposed molecular structures of both isolated kinetic and thermodynamic products. Complexation with iridium significantly enhances the in vitro activity of selected ligands against the chloroquine-sensitive (NF54) Plasmodium falciparum strain, with selected complexes being over one hundred times more active than their respective ligands. No cross-resistance was observed in the chloroquine-resistant (K1) strain. No cytotoxicity was observed for selected complexes tested against the mammalian Chinese Hamster Ovarian (CHO) cell line. In addition, speed-of-action assays and β-haematin inhibition studies were performed. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes can act as transfer hydrogenation catalysts, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of a hydrogen source, sodium formate.
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- author
- Melis, Diana R. ; Barnett, Christopher B. ; Wiesner, Lubbe ; Nordlander, Ebbe LU and Smith, Gregory S.
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Dalton Transactions
- volume
- 49
- issue
- 33
- pages
- 13 pages
- publisher
- Royal Society of Chemistry
- external identifiers
-
- scopus:85090073569
- pmid:32697227
- ISSN
- 1477-9226
- DOI
- 10.1039/d0dt01935f
- language
- English
- LU publication?
- yes
- id
- 032f91ca-f853-46ae-9fcd-554bc29d4c53
- date added to LUP
- 2020-09-24 15:11:59
- date last changed
- 2024-06-13 23:16:42
@article{032f91ca-f853-46ae-9fcd-554bc29d4c53,
abstract = {{<p>Iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against the Plasmodium falciparum malaria parasite. Supporting computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming a kinetic product that, upon heating over time, forms a more stable cyclometallated thermodynamic product. Single crystal X-ray diffraction confirmed the proposed molecular structures of both isolated kinetic and thermodynamic products. Complexation with iridium significantly enhances the in vitro activity of selected ligands against the chloroquine-sensitive (NF54) Plasmodium falciparum strain, with selected complexes being over one hundred times more active than their respective ligands. No cross-resistance was observed in the chloroquine-resistant (K1) strain. No cytotoxicity was observed for selected complexes tested against the mammalian Chinese Hamster Ovarian (CHO) cell line. In addition, speed-of-action assays and β-haematin inhibition studies were performed. Through preliminary qualitative and quantitative cell-free experiments, it was found that the two most active neutral, cyclometallated complexes can act as transfer hydrogenation catalysts, by reducing β-nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of a hydrogen source, sodium formate.</p>}},
author = {{Melis, Diana R. and Barnett, Christopher B. and Wiesner, Lubbe and Nordlander, Ebbe and Smith, Gregory S.}},
issn = {{1477-9226}},
language = {{eng}},
number = {{33}},
pages = {{11543--11555}},
publisher = {{Royal Society of Chemistry}},
series = {{Dalton Transactions}},
title = {{Quinoline-triazole half-sandwich iridium(iii) complexes : Synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies}},
url = {{http://dx.doi.org/10.1039/d0dt01935f}},
doi = {{10.1039/d0dt01935f}},
volume = {{49}},
year = {{2020}},
}