Exploring the anticancer properties of indenyl and allyl palladates through their interaction with nucleic acids

In this work, we analyse the mechanistic features of the interaction of indenyl (1-Ind) and allyl (2-All) palladates with nucleic acids (NAs) such as DNA (natural, poly(dA)-poly(dT) and poly(dG)-poly(dC)), RNA (in double and triple helices) and non-canonical structures of DNA (G-quadruplex and i-motif). Spectrophotometric titrations under different temperature and salt content conditions, viscosimetric experiments, fluorescent intercalator displacement (FID) tests together with theoretical Density Functional Theory (DFT)/Docking calculations are used to enlighten the complicated features of the interaction. The binding occurs in the grooves of the polynucleotides and is dominated by the geometrical features of the NA. A strong affinity for RNA double helix is present, together with interesting binding signatures to G-quadruplex and i-motif. The indenyl moiety plays a role and the binding is tighter (1-Ind > 2-All) for all NA systems. However, it is 2-All that, interestingly, shows the more striking differences in changing from one NA to another. The formation of covalent adducts and other mechanistic features are also discussed.