Multinuclear ruthenium(II) complexes as anticancer agents

Gorle, AK; Ammit, AJ; Wallace, L; Keene, FR; Collins, JG

Multinuclear ruthenium(II) complexes as anticancer agents

Gorle, AK

Ammit, AJ

Wallace, L Keene, FR Collins, JG

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Publication Type:: Journal Article
Citation:: New Journal of Chemistry, 2014, 38 (9), pp. 4049 - 4059
Issue Date:: 2014-01-01

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Field	Value	Language
dc.contributor.author	Gorle, AK https://orcid.org/0000-0001-7838-2625	en_US
dc.contributor.author	Ammit, AJ https://orcid.org/0000-0003-0555-2544	en_US
dc.contributor.author	Wallace, L	en_US
dc.contributor.author	Keene, FR	en_US
dc.contributor.author	Collins, JG	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	New Journal of Chemistry, 2014, 38 (9), pp. 4049 - 4059	en_US
dc.identifier.issn	1144-0546	en_US
dc.identifier.uri	http://hdl.handle.net/10453/115652
dc.description.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)(Me 2bpy)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. © the Partner Organisations 2014.	en_US
dc.relation.ispartof	New Journal of Chemistry	en_US
dc.relation.isbasedon	10.1039/c4nj00545g	en_US
dc.subject.classification	General Chemistry	en_US
dc.title	Multinuclear ruthenium(II) complexes as anticancer agents	en_US
dc.type	Journal Article
utslib.citation.volume	9	en_US
utslib.citation.volume	38	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	03 Chemical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	9	en_US
pubs.publication-status	Published	en_US
pubs.volume	38	en_US

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)(Me 2bpy)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. © the Partner Organisations 2014.

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