Esteves, TeresaXavier, CatarinaGama, SofiaMendes, FilipaRaposinho, Paula D.Marques, FernandaPaulo, AntónioPessoa, João CostaRino, JoséViola, GiampietroSantos, Isabel2012-10-252012-10-252010Org. Biomol. Chem., 2010, 8, 4104-41161477-0520http://dx.doi.org/10.1039/C0OB00073Fhttp://hdl.handle.net/10451/7119http://pubs.rsc.org/en/content/articlepdf/2010/ob/c0ob00073f© The Royal Society of Chemistry 2010New pyrazolyl-diamine ligands with acridine derivatives at the 4-position of the pyrazolyl ring were synthesized and characterized (L1 and L2). Coordination towards the fac-[M(CO)3]+ (M = Re, 99mTc) led to complexes fac-[M(CO)3(κ3-L)] (L = L1: M = Re1, Tc1; L = L2: M = Re2, Tc2). The interaction of the novel pyrazolyl-diamine ligands (L1 and L2) and rhenium(I) complexes (Re1 and Re2) with calf thymus DNA (CT-DNA) was investigated by a variety of techniques, namely UV-visible , fluorescence spectroscopy and circular and linear dichroism . Compounds L1 and Re1 have moderate affinity to CT-DNA and bind to DNA by intercalation, while L2 and Re2 have a poor affinity for CT-DNA. Moreover, LD measurements showed that L1 and Re1 act as perfect intercalators . By confocal fluorescence microscopy we found that L1 and Re1 internalize and localize in the nucleus of B16F1 murine melanoma cells . The congener Tc1 complex also targets the cell nucleus exhibiting a time-dependent cellular uptake and a fast and high nuclear internalization (67.2% of activity after 30 min). Plasmid DNA studies have shown that Tc1 converts supercoiled (sc) puc19 DNA to the open circular (oc) form.engAcridineFluorescence spectroscopyRadiopharmaceuticalsCell nucleusDNAjournal article