Buck, Damian P., Paul, Jacob A., Pisani, Michelle J., Collins, J. Grant, and Keene, F. Richard (2010) Binding of a flexibly-linked dinuclear ruthenium(II) complex to adenine-bulged DNA duplexes. Australian Journal of Chemistry, 63 (9). pp. 1365-1375.

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Abstract

Using 1H NMR spectroscopy and molecular modelling, the DNA binding of a chiral dinuclear ruthenium(ii) complex {,-[{Ru(phen)2}2(μ-bb7)]4+; phen=1,10-phenanthroline, bb7 =1,7-bis[4(4-methyl-2,2-bipyridyl)]-heptane} involving a bridging ligand containing a flexible aliphatic chain has been studied.The binding of the ruthenium(ii) complex was examined with the non-self-complementary duplexes d(CCGAGAATCGGCC):d(GGCCGATTCCGG) (containing a single adenine bulge: designated SB) and d(CCGAGCCGTGCC):d(GGCACGAGCCGG) (containing two adenine bulge sites separated by two base-pairs: designated DB). The NMR data indicated that the ruthenium(ii) complex bound at the bulge site of SB, with one ruthenium centre located at the bulge site with the second metal centre binding with lower affinity and selectivity in the duplex region adjacent to the bulge site. Less specific binding is inferred from chemical shift changes of nucleotide protons two to five base pairs from the single adenine bulge. The ruthenium(ii) complex selectively bound the DB duplex with one metal centre located at each bulge site. The NMR results also suggested that the metal complex binding induced greater changes to the structure of the SB duplex, compared with the DB duplex. Modelling indicates the bridging ligand allowed each ruthenium(ii) metal centre to bind one adenine bulge of the doubly-bulged duplex without disrupting the DNA structure, using the additional torsional flexibility conferred by the aliphatic bridging ligand. However, the second ruthenium(ii) metal centre is not able to bind in the minor groove of the singly-bulged duplex without disrupting the structure, as the metal centre is too bulky. The results of this study suggest dinuclear ruthenium(ii) complexes have considerable potential as probes for DNA and RNA sequences that contain two bulge sites separated by a small number of base-pairs.

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