Síntese, caracterização e estudos biológicos de complexos de Pt(II) e Pd(II) contendo ácido gálico e derivados

Abstract

The area of medicinal inorganic chemistry is concerned with the development of drugs based on a metal, as well as increasing the effectiveness and safety of metallopharmaceuticals already introduced into clinical practices. Within this context, the rational synthesis of new coordination compounds containing bioactive molecules is an interesting strategy, since the compounds obtained may be more effective and present different mechanisms of action than commercial drugs, making them promising for evaluation against resistant cells in chemotherapy regimens. Therefore, the objective of this work was to carry out the synthesis, characterization and biological studies of nine new complexes, four of Pd(II) and five of Pt(II) of the type [M(L)(PPh3)2] and [M(L)(phen)], where L = gallic acid and derivatives. The coordination compounds obtained were characterized by elemental analysis, conductimetric analysis, thermal analysis, spectroscopy in the ultraviolet-visible (UV-vis) and infrared (IR) region, nuclear magnetic resonance (1H, 13C, 31P) and X-ray diffraction in single crystal (complex 7). Using spectroscopic and X-ray diffraction techniques, it was possible to verify that gallic acid and its derivatives coordinated with the metal through phenolic hydroxyls in meta and para positions, after deprotonation. Additionally, the presence of hydration water molecules was verified for the Pd(II) complexes containing phenanthroline in their coordination sphere. The molar conductivity values for solutions with a concentration equal to 1 x 10-3 mol/L inferred that all complexes are non-electrolytes. Two tumor lines (TG180 and B16-F10) and their respective normal cell lines (C2C12 and NIH3T3) were used to evaluate the cell viability of the new complexes and it was possible to observe the importance of the presence of morpholine in the R group of the gallic acid derivative, where its respective complex presented the best result among the compounds tested with a selectivity index (SI) of 1.54. In the antituberculosis assay, complexes 1 and 7 stand out with activity values closer to those of the positive controls used in relation to the other complexes, both coordinated with two triphenylphosphine molecules, however with different gallic acid derivatives completing their respective coordination spheres.