Initial DNA Interactions of the Binuclear Threading Intercalator Λ,Λ-[μ-bidppz(bipy)4Ru2]4+: An NMR Study with [d(CGCGAATTCGCG)]2
Journal article, 2013

Binuclear polypyridine ruthenium compounds have been shown to slowly intercalate into DNA, following a fast initial binding on the DNA surface. For these compounds, intercalation requires threading of a bulky substituent, containing one RuII, through the DNA base-pair stack, and the accompanying DNA duplex distortions are much more severe than with intercalation of mononuclear compounds. Structural understanding of the process of intercalation may greatly gain from a characterisation of the initial interactions between binuclear RuII compounds and DNA. We report a structural NMR study on the binuclear RuII intercalator L,L-B (L,L-[m-bidppz- (bipy)4Ru2] 4+; bidppz=11,11’-bis(dipyrido[3,2-a:2’,3’-c]phenazinyl, bipy = 2,2’-bipyridine) mixed with the palindromic DNA [d(CGCGAATTCGCG)]2. Threading of L,L-B depends on the presence and length of AT stretches in the DNA. Therefore, the latter was selected to promote initial binding, but due to the short stretch of AT base pairs, final intercalation is prevented. Structural calculations provide a model for the interaction: L,L-B is trapped in a well-defined surface-bound state consisting of an eccentric minor-groove binding. Most of the interaction enthalpy originates from electrostatic and van der Waals contacts, whereas intermolecular hydrogen bonds may help to define a unique position of L,L-B. Molecular dynamics simulations show that this minor-groove binding mode is stable on a nanosecond scale. To the best of our knowledge, this is the first structural study by NMR spectroscopy on a binuclear Ru compound bound to DNA. In the calculated structure, one of the positively charged Ru2+ moieties is near the central AATT region; this is favourable in view of potential intercalation as observed by optical methods for DNA with longer AT stretches. Circular dichroism (CD) spectroscopy suggests that a similar binding geometry is formed in mixtures of L,L-B with natural calf thymus DNA. The present minor-groove binding mode is proposed to represent the initial surface interactions of binuclear RuII compounds prior to intercalation into ATrich DNA.

intercalation

DNA

NMR

ruthenium

Author

Lisha Wu

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Anna Reymer

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Christer Persson

University of Gothenburg

Krzysztof Kazimierczuk

University of Warsaw

Tom Brown

University of Southampton

Per Lincoln

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Bengt Nordén

Chalmers, Chemical and Biological Engineering, Physical Chemistry

Martin Billeter

University of Gothenburg

Chemistry - A European Journal

0947-6539 (ISSN) 1521-3765 (eISSN)

Vol. 19 17 5401-5410

Supramolecular Motive Power (SUMO)

European Commission (EC) (EC/FP7/227700), 2009-01-01 -- 2014-12-31.

Subject Categories

Physical Chemistry

Biochemistry and Molecular Biology

Biophysics

DOI

10.1002/chem.201203175

More information

Latest update

3/2/2022 3