The involvement of non-canonical DNA structures, such as Gquadruplex (G4) DNA, in cancer development and progression has set the pace towards the renaissance of DNA-binding metal complexes. In this work, we report the DNA-binding of three Ni(II), Cu(II), Zn(II) complexes of a salphen-like N 4 -donor ligand, bearing two imidazole groups condensed with a phenylenediamine moiety. Both duplex and G4 DNAs derived from human telomeres (hTelo), and a sequence mimicking the promoter of the oncogene myc (c-myc) were studied. UV-Vis and circular dichroism spectroscopic binding studies pointed out that, while all the three complexes bind the selected oligonucleotides, the Cu(II) derivative is the strongest and G4-selective compound of the series. Lastly, FRET DNA melting assay results on the Cu(II) complex/hTelo G4 system were interpreted by a loop-binding mechanism of interaction, as corroborated by molecular dynamics (MD) simulations.Metal-based compounds have generated wide interest in several fields of medicinal chemistry for their multiple application, spanning from bioimaging agents to potential drugs with antiparasitic, antibacterial, antirheumatic or anticancer effects, [a
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