Ruthenium polypyridyl complexes and their modes of interaction with DNA

is there a correlation between these interactions and the antitumor activity of the compounds?

Eva Corral, Anna C G Hotze, Hans Den Dulk, Anna Leczkowska, Alison Rodger, Michael J. Hannon, Jan Reedijk

Research output: Contribution to journalArticle

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Abstract

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy)L1L 2](2-n)+, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{μ-H2N(CH2) 6NH2}]4+. The ligand tpy is 2,2:6,2-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,2-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L 2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure-activity relationships that might be used to guide optimization of the activity of agents of this class of compounds.

Original languageEnglish
Pages (from-to)439-448
Number of pages10
JournalJournal of Biological Inorganic Chemistry
Volume14
Issue number3
DOIs
Publication statusPublished - Mar 2009
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2008. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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