Dinuclear ruthenium(II) complexes with flexible bridges as non-duplex DNA binding agents

Morgan, Joy L., Spillane, Caitriona B., Smith, Jayden A., Buck, Damian P., Collins, J. Grant, and Keene, F. Richard (2007) Dinuclear ruthenium(II) complexes with flexible bridges as non-duplex DNA binding agents. Dalton Transactions, 38. pp. 4333-4342.

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Abstract

The stereoisomers of a series of dinuclear ruthenium(II) complexes [{Ru(phen)2}2(µ-BL)]4+ (phen = 1,10-phenanthroline) with flexible bridging ligands (BL) bb2 {1,2-bis[4(4'-methyl-2,2'-bipyridyl)]ethane}, bb5 {1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane}, bb7 {1,7-bis[4(4'-methyl-2,2'-bipyridyl)]heptane}, and bb10 {1,10-bis[4(4'-methyl-2,2'-bipyridyl)]decane} have been synthesised. Their binding to a control dodecanucleotide, d(CCGGAATTCCGG)2, and a tridecanucleotide, d(CCGAGAATTCCGG)2, which contains a single adenine bulge have been studied using fluorescence displacement assays involving intercalating and groove-binding dyes, equilibrium dialysis and binding affinity chromatography. The fluorescence intercalator displacement (FID) assay indicated that -[{Ru(phen)2}2(µ-bb7)]4+ had the greatest binding affinity with all the oligonucleotides, whereas an analogous fluorescence technique using a minor-groove binding dye, equilibrium dialysis and affinity binding chromatography showed that -[{Ru(phen)2}2(µ-bb7)]4+ had the strongest binding. An 1H NMR study of the binding of the -enantiomer of [{Ru(phen)2}2(µ-bb7)]4+ to d(CCGAGAATTCCGG)2 confirmed the selectivity of the metal complex for the bulge site and provided the basis for an energy-minimised binding model of the dinuclear ruthenium complex with the single adenine bulge containing trinucleotide. The binding model demonstrated the ability of the flexibly-linked complex to follow the curvature of the DNA minor groove.

Item ID: 2811
Item Type: Article (Research - C1)
ISSN: 1477-9234
Keywords: DNA binding; NMR spectroscopy; bulge DNA; dinuclear ruthenium; flexible bridge; groove binding
Date Deposited: 08 May 2009 01:00
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030207 Transition Metal Chemistry @ 50%
03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 100%
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