Interaction of iron II complexes with B-DNA. Insights from molecular modeling, spectroscopy and cellular biology

Hugo Gattuso (1) , Thibaut Duchanois (1) , Vanessa Besancenot (2) , Claire Barbieux (2) , Xavier Assfeld (1) , Philippe Becuwe (2) , Philippe Gros (1) , Stéphanie Grandemange (2) , Antonio Monari (1)

1 SRSMC - Structure et Réactivité des Systèmes Moléculaires Complexes
2 CRAN - Centre de Recherche en Automatique de Nancy

We report the characterization of the interaction between B-DNA and three terpyridin iron II complexes. Relatively long time-scale molecular dynamics is used in order to characterize the stable interaction modes. By means of molecular modeling and UV-vis spectroscopy, we prove that they may lead to stable interactions with the DNA duplex. Furthermore, the presence of larger π-conjugated moieties also leads to the appearance of intercalation binding mode. Non-covalent stabilizing interactions between the iron complexes and the DNA are also characterized and evidenced by the analysis of the gradient of the electronic density. Finally, the structural deformations induced on the DNA in the different binding modes are also evidenced. The synthesis and chemical characterization of the three complexes is reported, as well as their absorption spectra in presence of DNA duplexes to prove the interaction with DNA. Finally, their effects on human cell cultures have also been evidenced to further enlighten their biological effects.

Mots clés: Non Covalent Interactions; Cell viability; Molecular modeling; Iron complexes; DNA Sensitization

Domaines: Chimie thérapeutique; Chimie de coordination

Hugo Gattuso, Thibaut Duchanois, Vanessa Besancenot, Claire Barbieux, Xavier Assfeld, et al.. Interaction of iron II complexes with B-DNA. Insights from molecular modeling, spectroscopy and cellular biology. Frontiers in Chemistry, 2015, 3 (67), ⟨10.3389/fchem.2015.00067⟩. ⟨hal-01242500⟩