Complexos de Cu1 e Ag1 com tiossemicarbazidas derivadas da p-toluenosulfohidrazida: síntese, caracterização , estudos de luminescência e atividade biológica

Abstract

This work consists in the synthesis and characterization of CuI and AgI complexes with thiosemicarbazides derived from p-toluenesulfohydrazide aiming to obtain compounds with luminescent and pharmacological properties. The complexing agents were obtained by reactions of p-toluenesulfohydrazide with a R-isothiocyanate (L1Ch: R = cyclohexyl and L2Ph: R = phenyl) in order to obtain ligands containing two pharmacologically active classes, the sulfonamides and thiosemicarbazides. Reactions of the ligands with the precursor [CuCl(PPh3)3] afforded neutral CuI tetrahedral complexes of the type [CuICl(PPh3)2(L1R)], while the reactions with AgNO3 led to the formation of ionic complexes with linear geometry of the type [AgI(L1R)2]NO3. All the complexes were obtained as colorless crystalline solids with yields around 70%. The free ligands and complexes were properly characterized by the following techniques: elemental analysis (CHNS), melting point, absorption spectroscopies in the infrared region and UV-Vis, NMR 1H and 31P{1H}, mass spectrometry and single crystal X-ray diffraction. In addition to the structural elucidation, the compounds were evaluated for their photophysical properties. The emission was verified and the quantum yield of each compound determined. Beyond this technique, theoretical calculations were performed to understand the nature of the transitions involved in the formation of the excited state of the complexes. By the data obtained, it was observed that the substituent group of the ligands (cyclohexyl or phenyl) affects the transitions involved. Furthermore, the luminescence studies indicate that the emission of the compounds can be tuned by the type of substituents in the peripheral structure of the ligands. Biological tests against Mycobacterium tuberculosis strain showed that the free ligands and complexes do not present activity at the concentration of 25 μg/mL. On the other hand, antitumor activity tests against skin cancer cells showed that the complexation leads to a considerable increase of the activity, being all the complexes more active than cisplatin and free ligands after a period of 48 h of incubation. In addition, two complexes showed excellent activity against T. cruzi intracellular strains, with similar selectivity indexes as the standard drug benznidazole.