Structural Characterization and Cytotoxic Activity of Heteroleptic Copper (II) Complexes with L-Dipeptides and 5-NO2-Phenanthroline. Crystal Structure of [Cu(Phe- Ala)(5-NO2-Phen)].4H2O

Sebastian Iglesias, Natalia Al

Abstract

Objective: To prepare a new series of [Cu(L-dipeptide)(5-NO2-phen)] complexes and study the influence of the nitro group on the structure, DNA interaction and cytotoxic activity, aimed at finding new copper compounds with antitumor activity. Methodology and results: A series of mononuclear mixed ligand copper(II) complexes of the type [Cu(L-dipeptide)(5-NO2-phen)]·nH2O (where L-dipeptide: Ala-Phe, Phe-Ala, Phe-Val and Phe-Phe) were synthesized and characterized. The crystal structure of [Cu(Phe-Ala)(5-NO2-phen)]?4H2O was solved by X-Ray diffraction. The complexes present square-based pyramidal coordination geometry. UV-Vis spectroscopy results suggest that the coordination observed in solid state is maintained in solution. The complexes bind to isolated DNA, as studied by Circular Dichroism. Biological experiments showed that all the complexes induce cell death in HeLa (human cervical adenocarcinoma) and MDA-MB-231 (human metastatic breast adenocarcinoma) cell lines. Their cytotoxic activity is higher than that of the Cisplatin. Conclusions: Four new [Cu(L-dipeptide)(5-NO2-phen)]·nH2O were prepared, which present good cytotoxic activity. The introduction of the nitro group on the phen impaired DNA binding and cytotoxic activity.