CuII complexes with N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)benzamides: Synthesis, characterization and biological evaluation

4-Fluoro-N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)benzamide (HL1) and 2,3,4,5,6-pentafluoro-N-(5-(methylthio)-1,3,4-thiadiazol-2-yl)benzamide (HL2) were prepared through reaction with 2-amino-5-(methylthio)-1,3,4-thiadiazole and the corresponding aroyl chlorides. They have a planar cis-orientation concerning the carboxamide oxygen atom and the thiadiazole sulfur atom. The short intramolecular S∙∙∙O contact upon the cis-orientation in HL1 was studied by DFT calculations. The HL molecules are luminescent in the solid-state and solution. The reaction of HL1 with CuCl2∙2H2O in methanol/dichloromethane mixture produces [Cu(CH3OH)2Cl2(HL1)2] (1) and [Cu(L1)2] (2). Compound 2 is formed when NEt3 is used, or the used copper salt is replaced by Cu(Ac)2∙H2O. Given the low solubility of compound 2, a reaction of HL2 with CuCl2∙2H2O was performed in methanol with the addition of NEt3 as supporting base, yielding [Cu(L2)2] (3) and polymorph 3B. The molecular structures of the products were determined by single-crystal XRD. All compounds were characterized by elemental analysis, FT-IR and UV-Vis/DRS spectroscopies, and ESI mass spectrometry. HL1, HL2 and compound 1 were also analyzed by NMR spectroscopy. HL1, HL2, and complexes 1 and 3 were evaluated for their cytotoxicity against MCF-7 cells and non-tumorigenic HaCaT cells. Complexes 1 and 3 exhibited cytotoxic activity against MCF-7, with CC₅₀ values of 5.02 ± 1.97 µM and 7.88 ± 2.16 µM, respectively, while the ligands HL1 and HL2 are non-cytotoxic at the tested concentrations.