Pd(II)/1,10-phenanthroline complexes bearing arene ligands: On the role of N- vs O-coordination to tune their cellular activity and binding ability towards DNA and RNA

Three Pd(II)-based complexes of 1,10-phenanthroline and N- or O-coordinating ligands have been synthesised and tested with different relevant biosubstrates like double-stranded DNA, double and triple helix of RNA, DNA G-quadruplexes of different conformations and bovine serum albumin. Here a correlation between N- vs O-coordinating elements and binding mechanism emerged, where the N-coordinating ligands proved to be the most promising. These outcomes were confirmed also in the cellular experiments. The Pd(II) complex with naphthalene-1,8-diamine is the one that is able to be carried by BSA, to strongly bind nucleic acids, to produce reactive oxygen species (ROS) and to show the best cellular performances (poorly toxic towards healthy cells and highly toxic against the cisplatin-resistant cancer cell line). On the opposite, the complex with benzene-1,2-diolate may be sequestered by BSA, weakly binds nucleic acids, does not produce ROS and shows poor cellular activity. The complex with benzene-1,2-diamine stays in between. Other mechanistic details are discussed which show that the biophysical behaviour is the sum of the contribution of aromaticity, charge and N- or O-coordination. Graphical abstract Some Pd(II)-L-phen complexes where phen = phenanthroline and L is either N- or O-coordinating ligands were synthesised tested as for DNA/RNA/G4/BSA binding and cellular activity. The N-coordinated ones resulted to be the only producing ROS, intercalating in nucleic acids and showing improved cellular performances. Other details are discussed. [Display omitted] •N- or O-coordinated Pd(II) complexes were synthesised and compared as bio-activity.•The binding mechanism to DNA/RNA/G4/BSA and cellular activity was studied.•Pd(II) complexes with N-coordinating ligands produce ROS and intercalate into DNA.•A N-coordinated Pd(II) complex is very active and selective towards cancer cells.•Pd(II) complex with O-coordinating ligand seems sequestrated by albumin.