The influence of thioether-substituted ligands in dicopper(II) complexes: Enhancing oxidation and biological activities.

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = -2.27 cm-1 and -5.01 cm-1, respectively, H = -2JS1S2) and ferromagnetic coupling for 2 (J = 5.72 cm-1). Broken symmetry DFT calculations attribute this behavior to a major contribution from the dz2 orbitals for 1 and 3, and from the dx2-y2 orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with kcat of (90.79 ± 2.90) × 10-3 for 1, (64.21 ± 0.99) × 10-3 for 2 and (14.20 ± 0.32) × 10-3 s-1 for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

Enhancing the biological properties of zinc complexes with bis(indolyl)methane groups: Synthesis, characterization, DNA interaction, and biocide activity.

The unprecedented mononucleated ligand (6,6-di(1H-indol-3-yl)-N,N-bis(pyridin-2-ylmethyl)hexan-1-amine (LC5) with an N3-donor set and its complexes [Zn(LC5)Cl2] • 2CH3OH (1) and [Zn(LC5)2](ClO4)2 (2), were successfully prepared. All compounds were fully characterized by a suite of physicochemical methods. Fluid 1H and 13C NMR spectroscopy, as well as DFT and TD-DFT calculations, were carried out to propose a viable structural arrangement for both complexes. The interaction between these compounds and DNA was monitored in the UV region where binding constants (Kb) were estimated (2 > 1 > LC5). These data were corroborated by DNA cleavage assays using groove binders, circular dichroism, and docking studies. Both complexes confirmed their biocide activity against selected microorganisms: Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria, the filamentous fungi A. fumigatus and S. cerevisiae. Finally, the cytotoxic activities of 1 and 2 were tested against the erythroleukemia K562 cell line. For all biological studies, it was probed that the presence of the indole moieties and the zinc atoms in the chemical composition of the complexes studied could increase the magnitude of the activity following the order: 2 > 1 > LC5, where a linear relationship between the biological activity upon K562 cells (IC50) and DNA binding studies (Kb) was found.