Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/91158
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Type: Journal article
Title: Multinuclear ruthenium(II) complexes as anticancer agents
Author: Gorle, A.
Ammit, A.
Wallace, L.
Keene, F.
Collins, J.
Citation: New Journal of Chemistry, 2014; 38(9):4049-4059
Publisher: Royal Society of Chemistry
Issue Date: 2014
ISSN: 1144-0546
1369-9261
Statement of
Responsibility: 
Anil K. Gorle, Alaina J. Ammit, Lynne Wallace, F. Richard Keene, and J. Grant Collins
Abstract: A series of dinuclear ruthenium(II) complexes that contain labile chlorido ligands, [{Ru(tpy)Cl}2{μ-bbn}]2+ {designated Cl-Rubbn; tpy = 2,2′:6′,2′′-terpyridine, bbn = bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (n = 7, 10, 12, 14 or 16)} and derivatives containing nitro substituents on the tpy ligand and/or secondary amines within the bbn linking chain have been synthesised and their potential as anticancer agents examined. Some of the Cl-Rubbn species showed good anticancer activity against MCF-7 and MDA-MB-231 breast cancer cell lines, with the Cl-Rubb12 complex being four-times more active than cisplatin. Inclusion of nitro substituents on the tpy ligands of Cl-Rubb12 resulted in significantly decreased anticancer activity. The incorporation of amine groups into the linking ligand did not increase the anticancer activity of the Cl-Rubbn complexes. The Cl-Rubbn complexes and those containing amine groups in the linking chain aquated at approximately the same rate, with 50% aquation within 120 minutes. By comparison, the complexes containing nitro substituents on the tpy ligand aquated extremely slowly, with 60% of the chlorido complex remaining 24 hours after they were dissolved in water. Cyclic voltammetry with the model mononuclear complex [Ru{(NO2)3tpy}(Me2bpy)Cl]+ {(NO2)3tpy = 4,4′,4′′-trinitro-2,2′:6′,2′′-terpyridine} showed that the nitro substituents exerted a strong effect on the ruthenium centre, with the anodic peak corresponding to the Ru(III/II) couple shifted positively by 300 mV compared to that from the non-nitrated parent complex [Ru(tpy)(Me2bpy)Cl]+. 1H NMR studies of the reaction of the Cl-Rubbn complexes with GMP indicated that the ruthenium complexes covalently bound the nucleotide slowly, with 33% bound in 24 hours. However, the results of this study suggest that the cytotoxicity of the dinuclear ruthenium complexes is a combination of covalent and reversible binding with DNA.
Rights: This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
RMID: 0030009352
DOI: 10.1039/c4nj00545g
Appears in Collections:Physics publications

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