Síntese, caracterização, reatividade e ensaios biológicos de complexos de ferro com ligantes macrocíclicos cyclam mono-N-funcionalizados com grupos fluoróforos.

Abstract

The main goal of this work is to contribute to the chemistry of Fe(III) metal complexes with the cyclam ligand and its derivatives. This was achieved through the synthesis, characterization, reactivity studies, and cytotoxicity essays of novel complexes using mono-N-functionalized cyclam appended with fluorophores. The novel general formulas of the novel complexes are a follow [Fe(Ln)Cl2]Cl, with n values of 1 (cyclam), 2 (1-naphthalen-2-ylmethyl-cyclam), 3 (1-anthracen-9-ylmethyl-cyclam), and 4 (1-pyren-1-ylmethyl-cyclam). The synthetic approach for ligands resulted in good yields. In general, the results of ligand characterizations agree with the proposed composition and structure and confirm the presence of the attached fluorophores. The iron(III) complexes obtained were characterized by different techniques such as: elemental analysis (CHN), UV-Vis electronic absorption and fluorescence emission, IR vibrational, EPR spectroscopies and electron spray ionization mass spectrometry (ESI-MS). Electrochemical techniques, such as voltammetry and direct potentiometry, were also carried out with the aim of both characterizing the complexes and investigating their reactivity regarding the lability of the chloride ligands. Due to the planar structures of the N-appended fluorophores, which may interact with biologically relevant macromolecules or exhibit activity against pathogens, in vitro tests on tumor cells were carried out. Results of elemental analysis showed good agreement between the calculated and the experimental values, assuming that the complexes are in monohydrate form. The UV-Vis electronic absorption and fluorescence emission spectra are largely dominated by the fluorophore bands. The IR spectra exhibited the main characteristic bands of both the macrocyclic ligand and the fluorophores. From the EPR data, it was observed that g values are similar (regions of 7.0, 4.3 and 2.0) for the Fe(III) complexes. These results also indicate that the novel complexes have the same geometry, which is consistent with the cis isomeric form. In the cyclic voltammograms, a quasi-reversible pair of peaks was observed in the range of -0.5 to 0.5 V, which was attributed to the Fe3+/2+ redox couple in the complexes. Studies of reactivity regarding chloride lability were conducted by cyclic voltammetry and direct potentiometry, and suggesting a low lability of the coordinated chlorides in these complexes. In vitro cytotoxicity assays were performed on free ligands and complexes using non-tumorigenic MCF10 cells, cancer lines MCF7, MB231 and PC3. The L1 ligand and complex did not exhibit activity (IC50 > 50 μM) against any of the tested strains. Conversely, both the L4 ligand and the [FeCl2(L4)]Cl complex demonstrated the highest activity against the strains under investigation.