Odachowski, M, Neven, R, Perversi, G et al. (7 more authors) (2023) Ionic mononuclear [Fe] and heterodinuclear [Fe,Ru] bis(diphenylphosphino)alkane complexes: Synthesis, spectroscopy, DFT structures, cytotoxicity, and biomolecular interactions. Journal of Inorganic Biochemistry, 242. 112156. ISSN 0162-0134
Abstract
Iron(II) and Ru(II) half-sandwich compounds encompass some promising pre-clinical anticancer agents whose efficacy may be tuned by structural modification of the coordinated ligands. Here, we combine two such bioactive metal centres in cationic bis(diphenylphosphino)alkane-bridged heterodinuclear [Fe2+, Ru2+] complexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(η5–C5H5)Fe(CO)2(κ1–PPh2(CH2)nPPh2)]{PF6} (n = 1–5), compounds 1–5, and heterodinuclear [Fe2+, Ru2+] complexes, [(η5–C5H5)Fe(CO)2(μ–PPh2(CH2)nPPh2))(η6–p–cymene)RuCl2]{PF6} (n = 2–5) (compounds 7–10), were synthesized and characterised. The mononuclear complexes were moderately cytotoxic against two ovarian cancer cell lines (A2780 and cisplatin resistant A2780cis) with IC50 values ranging from 2.3 ± 0.5 μM to 9.0 ± 1.4 μM. For 7–10, the cytotoxicity increased with increasing Fe⋅⋅⋅Ru distance, consistent with their DNA affinity. UV–visible spectroscopy suggested the chloride ligands in heterodinuclear 8–10 undergo stepwise substitution by water on the timescale of the DNA interaction experiments, probably affording the species [RuCl(OH2)(η6-p-cymene)(PRPh2)]2+ and [Ru(OH)(OH2)(η6-p-cymene)(PRPh2)]2+ (where PRPh2 has R = [−(CH2)5PPh2–Fe(C5H5)(CO)2]+). One interpretation of the combined DNA-interaction and kinetic data is that the mono(aqua) complex may interact with dsDNA through nucleobase coordination. Heterodinuclear 10 reacts with glutathione (GSH) to form stable mono- and bis(thiolate) adducts, 10-SG and 10-SG2, with no evidence of metal ion reduction (k1 = 1.07 ± 0.17 × 10−1 min−1 and k2 = 6.04 ± 0.59 × 10−3 min−1 at 37 °C). This work highlights the synergistic effect of the Fe2+/Ru2+ centres on both the cytotoxicity and biomolecular interactions of the present heterodinuclear complexes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 Elsevier Inc. All rights reserved. This is an author produced version of an article published in Journal of Inorganic Biochemistry made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0) in accordance with the publisher's self-archiving policy. |
Keywords: | Ruthenium; Metallodrug; Cytotoxic; DNA-binding; Glutathione coordination |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Physical Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 Jun 2023 14:54 |
Last Modified: | 04 Feb 2024 01:13 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jinorgbio.2023.112156 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:200669 |
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