Síntese, caracterização e estudo biológico de compostos de coordenação heterolépticos de cobre(I) com sulfonamidas e trifenilfosfina

Abstract

Tuberculosis (TB) is a global health challenge, caused by Mycobacterium tuberculosis (Mtb), which was identified by Robert Koch in 1882. In 2022, TB affected 10.6 million people, resulting in 1.3 million deaths. In 2024, in Brazil, Roraima was the Brazilian state with the highest TB incidence rate, with 85.7 cases per 100.000 inhabitants. TB’s treatment is based on combination of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol, administered in two phases. However, this approach faces challenges, such as the development of resistance of Mtb to the drugs. Several research groups are working to overcome these limitations, with emphasis on the synthesis pf metal complexes. In this work, three compounds were synthesized using Copper (I) chloride, sulfadiazine (SD), sulfamerazine (SM) and sulfapyridine (SPY) as primary ligands and triphenylphosphine (PPh3) acting as secondary ligand. The complexes [Cu2(µCl)2(Sulfa)2(PPh3)2], where Sulfa = SD or SM or SPY, were obtained, by 1:1:1 stoichiometric ratio. All the compounds were characterized by Elemental and Thermal Analyses (TG/DTA), InfraRed (IR), Raman, Nuclear Magnetic Resonance (NMR, 1H, 13C, 31P, {1H,15N}), UltraViolet-Visible (UV-Vis) electronic absorption spectroscopies, and X-ray diffractometry on single crystals for [Cu2(µ-Cl)2(SM)2(PPh3)2] and [Cu2(µ-Cl)2(SPY)2(PPh3)2] and by polycrystals method for [Cu2(µ-Cl)2(SD)2(PPh3)2]. The studies confirmed the formation of the three Copper (I) compounds with sulfonamides and triphenylphosphine. Stability tests performed by NMR, molar conductivity and UV-Vis’s indicated that the complexes are stable in dimethylsulfoxide and acetonitrile for more than 24 hours. Biological tests were performed to determine the Minimum Inhibitory Concentration for 90% of the microbial population (MIC90) against Mycobacterium tuberculosis. The results indicated that the three copper(I) complexes with PPh3, combined with SD, SM, and SPY, exhibit activity against Mtb.