Ionic mononuclear [Fe] and heterodinuclear [Fe,Ru] bis (diphenylphosphino)alkane complexes: Synthesis, spectroscopy, DFT structures, cytotoxicity, and biomolecular interactions
| Autor: | Burgert Blom, Matylda Odachowski, Robin Neven, Giuditta Perversi, Dario Romano, Cathryn A. Slabber, Mouna Hadiji, Maarten Honing, Yuandi Zhao, Orde Q. Munro |
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| Přispěvatelé: | RS: FSE MSP, Maastricht Science Programme, Imaging Mass Spectrometry (IMS), RS: M4I - Imaging Mass Spectrometry (IMS) |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
History
Polymers and Plastics Cytotoxic Metallodrug ANTITUMOR METALLODRUGS Glutathione coordination IN-VITRO LIGANDS SYNTHESIS Biochemistry ARENE COMPLEXES Industrial and Manufacturing Engineering Ruthenium RUTHENIUM POLYPYRIDYL COMPLEXES HALF-SANDWICH COMPLEXES Inorganic Chemistry DNA-binding ORGANOMETALLIC RUTHENIUM(II) COMPOUND RAPTA-C BREAST-CANCER Business and International Management ANTICANCER COMPLEXES |
| Zdroj: | Journal of Inorganic Biochemistry, 242:112156. Elsevier Inc. |
| ISSN: | 0162-0134 |
| DOI: | 10.1016/j.jinorgbio.2023.112156 |
| Popis: | 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+] com-plexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(eta(5)-C5H5)Fe(CO)(2)(kappa(1)-PPh2(CH2)(n)PPh2)]{PF6} (n = 1-5), compounds 1-5, and heterodinuclear [Fe2+, Ru2+] complexes, [(eta(5)-C5H5)Fe(CO)(2)(mu-PPh2(CH2)nPPh(2)))(eta(6)-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 mu M to 9.0 +/- 1.4 mu M. For 7-10, the cytotoxicity increased with increasing Fe center dot center dot center dot 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)(eta(6)-p-cymene)(PRPh2)](2+) and [Ru(OH)(OH2)(eta(6)-p-cymene)(PRPh2)](2+) (where PRPh2 has R = [-(CH2)(5)PPh2-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-SG(2), with no evidence of metal ion reduction (k(1) = 1.07 +/- 0.17 x 10(-1) min(-1) and k(2) = 6.04 +/- 0.59 x 10-3 min(-1) at 37 degrees C). This work highlights the synergistic effect of the Fe2+/Ru2+ centres on both the cytotoxicity and biomolecular interactions of the present heterodinuclear complexes. |
| Databáze: | OpenAIRE |
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