Síntese e caracterização de novos complexos de ouro(I) e prata(I) com ligantes 1-tiocarbamoil-pirazolinas explorando propriedades fotofísicas e biológicas: Busca por novos agentes de bioimageamento celular

Abstract

Pyrazolines have in their main structure a non-aromatic five-membered ring with three carbon atoms and two adjacent nitrogen atoms. These molecules exhibit several biological activities such as antitumor, antibacterial, antiviral, analgesic, and antifungal activities, among others. In coordination chemistry, the complexation of ligands with biological properties is a strategy to enhance their biological properties and expand the range of applications of these compounds. This work describes the synthesis, structural and spectroscopic characterization, and investigation of the biological properties of six new pyrazoline complexes with AuI and AgI ions, which belong to three distinct classes of compounds ([Ph3PAuL]PF6.MeOH, [LAuCl], [L2AgCl]). The structures of the complexes were elucidated by X-ray diffractometry, showing a linear coordination environment for the gold (I) compounds and trigonal planar for the silver (I) complexes. Spectroscopic analyses demonstrated that the complexes were luminescent when excited in the 380 nm region, exhibiting emission in a broad spectrum range with lifetimes on the nanosecond scale. Biological evaluations demonstrate that the complexes are more active than their respective ligands in antibacterial and antitumor assays. In the antimicrobial assay, complexes 1 and 2 showed bactericidal action at a concentration of 1.95 μg/mL against strain 82H (resistant Staphylococcus epidermidis). The results of the antitumor assay showed excellent activity of complexes 1, 2, and 6, the most active against both proven tumor cultures. Against breast cancer cells (4T1), the mean inhibitory concentrations (IC50) were (C1) 2.9 ± 0.1, (C2) 2.5 ± 0.2, and (C6) 2.5 ± 0.1 (μM ± SD). The results for bioimaging showed that the complexes emitted blue fluorescence signals (420-440 nm); in the coordination compounds with ligand 2, the signals dispersed throughout the cytoplasm, without specificity for any particular cellular region. However, for the complexes using ligand 1, they were specific, (C1) staining of the lipid bodies of the cells, (C3) staining of the lysosomes/endosomes of the cells, and (C5) as mitochondria. The complete characterization of the synthesized complexes involved, in addition to X-ray diffractometry, elemental analysis of CHN, vibrational spectroscopy in the infrared region, and molecular absorption spectroscopy in the UV-Vis supported by TD-DFT calculations, high-resolution mass spectrometry, fluorescence spectroscopy, and 1H and 13C nuclear magnetic resonance.