Flexibility of short ds-DNA intercalated by a dipyridophenazine ligand.

We use Förster Resonant Energy Transfer (FRET) in order to measure the increase of flexibility of short ds-DNA induced by the intercalation of dipyridophenazine (dppz) ligand in between DNA base pairs. By using a DNA double strand fluorescently labeled at its extremities, it is shown that the end-to-end length increase of DNA due to the intercalation of one dppz ligand is smaller than the DNA base pair interdistance. This may be explained either by a local bending of the DNA or by an increase of its flexibility. The persistence length of the formed DNA/ligand is evaluated. The described structure may have implications in the photophysical damages induced by the complexation of DNA by organometallic molecules.

Complexation of DNA with ruthenium organometallic compounds: the high complexation ratio limit.

Interactions between DNA and ruthenium organometallic compounds are studied by using visible light absorption and circular dichroism measurements. A titration technique allowing for the absolute determination of the advancement degree of the complexation, without any assumption about the number of complexation modes is developed. When DNA is in excess, complexation involves intercalation of one of the organometallic compound ligands between DNA base pairs. But, in the high complexation ratio limit, where organometallic compounds are in excess relative to the DNA base pairs, a new mode of interaction is observed, in which the organometallic compound interacts weakly with DNA. The weak interaction mode, moreover, develops when all the DNA intercalation sites are occupied. A regime is reached in which one DNA base pair is linked to more than one organometallic compound.

UV-vis absorption spectrum of a novel Ru(II) complex intercalated in DNA: [Ru(2,2'-bipy)(dppz)(2,2'-ArPy)]⁺.

The synthesis of a new Ru(II) complex is reported. Its absorption spectrum when interacting with DNA in water was calculated at the hybrid quantum mechanics molecular mechanics level of theory and compared with experimental data. The vertical transitions were computed using time-dependent density functional theory in the linear response approximation. The complex and its environment were treated at the quantum mechanical and molecular mechanical levels, respectively. The effects of the environment were investigated in detail and conveniently classified into electrostatic and polarization effects. The latter were modeled using the computationally inexpensive "electronic response of the surroundings" method. It was found that the main features of the experimental spectrum are nicely reproduced by the theoretical calculations. Moreover, analysis of the most intense transitions utilizing the natural transition orbital formalism revealed important insights into their nature and their potential role in the irreversible oxidation of DNA, a phenomenon that could be relevant in the field of cancer therapy.

Spectral properties of polypyridyl ruthenium complexes intercalated in DNA: theoretical insights into the surrounding effects of [Ru(dppz)(bpy)2]2+.

The UV/Visible absorption properties of a polypyridyl ruthenium complex upon intercalation on DNA are studied at the mixed quantum mechanics molecular mechanics level of theory. Vertical excitation transitions are computed by time dependent density functional theory. Particular emphasis is put on the different levels at which the macromolecular environment is treated, and in particular on the analysis of the effect of mechanical, electrostatic and polarizable embedding. We show that with the highest level of theory the experimental absorption wavelengths are reproduced with a difference of only 2 or 3 nm for the low energy bands. The systematic analysis of the individual vertical transitions allows us to get much more insights into the role played by the environment, in particular, in metal to ligand and intra ligand charge transfer transitions that can lead to the production of DNA oxidative lesions exploitable in phototherapy.