Novos complexos de Cu(II) contendo ligantes monodentados derivados de 4-(fenilcalcogênio)-1H-pirazol (Se, S) e tridentados naftalato-imina: Síntese, caracterização, avaliação da atividade antioxidante e citotoxicidade

Abstract

Complexes 2a – 2c were characterized by single crystal X-ray diffraction, high resolution electrospray ionization mass spectrometry (ESI-HRMS), ultraviolet-visible (UV-vis) and infrared (IR) spectroscopy. Elemental analysis (C,H,N) of compounds 2a and 2b was performed to determine the purity of these compounds. Compounds 2a – 2c show characteristics in the solid state of mononuclear complexes, with coordination of two atoms of Npyrazole and two atoms of chlorine in front of the Cu(II) atom, with coordination number four and a quadratic geometry. Complex 2c, on the other hand, has characteristics of a dinuclear complex in the solid state, with the coordination number five, having a square pyramidal geometry. In solution, complex 2c was characterized as a monometallic species by ESI-HRMS. Complexes 2a and 2b were stable in DMSO solution for 24 h. We are interested in investigating the biological activities of coordination compounds containing copper as the metallic center. Thus, the new complexes 2a – 2c together with Cu(II) 2d – 2h complexes containing bidentate and tridentate naphthalate-imine ligands with NNO, ONO and SNO donor atoms were applied in in vitro tests to evaluate the antioxidant capacity of these new compounds . We investigated the ABTS+ and DPPH free radical scavenging capacity for both classes of compounds. Also, compounds 2a – 2b were evaluated in an ex-vivo test of inhibition of reactive species (RE). In the antioxidant evaluation assay, ligands 1a – 1c did not show antioxidant activity in the elimination of DPPH and ABTS+ radicals. Complexes 2a – 2c, on the other hand, presented IC50 of 4.0 ± 1.2 μM, 8.0 ± 0.5 μM and 3.7 ± 2.2 μM, respectively, in the elimination of the DPPH radical. In the elimination of the ABTS+ radical, an IC50 of 37.7 ± 1.8 μM was obtained for 2a. Compounds 2b and 2c did not show activity at the doses tested in ABTS+. In the elimination of reactive species, compound 2a showed better ER inhibition at 10 μM, compared to 2b, with elimination percentages of 63.6 ± 1.6% (2a) and 55.6 ± 4.1% (2b). In vitro cytotoxicity evaluations were performed using the V79 strain by the Neutral Red method. Ligands 1a – 1c and complexes 2a – 2c did not exhibit cytotoxicity on the V79 cell line at low concentrations, with IC50 reaching 63.6 μM (1a), 57.3 μM (2a), 54.3 μM (2b) and 41 .1 μM (2c). Stability studies in DMSO and PBS solution, as well as evaluation of the redox behavior were performed for Cu(II) complex class (2d-2h) containing bidentate and tridentate naphthalate-imine ligands by UV-Vis techniques and cyclic voltammetry, respectively. In the kinetic study, the compounds were stable in DMSO, however, in PBS they showed a slight hypochromic effect, which does not indicate structural alterations. All compounds showed redox activity, with relevant values of ΔE/mV for the 2d, 2f and 2h complexes. The evaluation of DPPH radical capture and ABTS+ radical cation was performed at different times. Complexes 2d, 2e, 2f and 2h showed activities in the elimination of the ABTS+ radical from the concentration of 5 μM, with percentages reaching 83.8 ± 0.1 %; 93.4 ± 0.2%; 52.1 ± 0.4%; 79.3 ± 0.6%, respectively. In the antioxidant evaluation in DPPH, with the exception of complex 2e, the complexes neutralized the DPPH radical from 20 μM, with percentages of 91.4 ± 1.4 (2d); 74.6 ± 7.7 (2f); 37.3 ± 6.8 (2g) and 95.2 ± 0.7 (2h).