Here, we report the antiproliferative/cytotoxic properties of 8-hydroxyquinoline (8-HQ) derivatives on HeLa cells in the presence of transition metal ions (Cu(2+), Fe(3+), Co(2+), Ni(2+)). Two series of ligands were tested, the arylvinylquinolinic L1-L8 and the arylethylenequinolinic L9-L16, which can all interact with metal ions by virtue of the N,O donor set of 8-HQ; however, only L9-L16 are flexible enough to bind the metal in a multidentate fashion, thus exploiting the additional donor functions. L1-L16 were tested for their cytotoxicity on HeLa cancer cells, both in the absence and in the presence of copper. Among them, the symmetric L14 exhibits the highest differential activity between the ligand alone (IC50 = 23.7 μM) and its copper complex (IC50 = 1.8 μM). This latter, besides causing a significant reduction of cell viability, is associated with a considerable accumulation of the metal inside the cells. Metal accumulation is also observed when the cells are incubated with L14 complexed with other late transition metal ions (Fe(3+), Co(2+), Ni(2+)), although the biological response of HeLa cells is different. In fact, while Ni/L14 and Co/L14 exert a cytostatic effect, both Cu/L14 and Fe/L14 trigger a caspase-independent paraptotic process, which results from the induction of a severe oxidative stress and the unfolded protein response.

This work examines the crystal structures of 15 Ag(I) complexes with thioether functionalized bis(pyrazolyl)-methane derivatives to rationalize the influence of the ligand on the formation of (a) coordination polymers (CPs), (b) oligonuclear (hexameric and dinuclear) complexes, and (c) mononuclear complexes. It was previously reported how this ligand class could generate microporous architectures with permanent porosity. Some ligand modifications could induce a cavity size modulation while preserving the same overall architecture. The bis(pyrazolyl)methane scaffold can be easily functionalized with various structural fragments; hence the structural outcomes were studied in this work using various ligand modifications and Ag(I) salts. In particular, six new ligand classes were prepared with the following features: (1) The steric hindrance on the pyrazole rings L 3,3 ′ Me , L 5,5 ′ Me , L 5,3 ′ Me , L CF3 , and L Br was modified.(2) The steric hindrance was reduced on the peripheral thioether group: L SMe . (3) Finally, the presence of fluorine and bromine atoms in L CF3 and L Br offered the possibility to expand the type of interaction with respect to the ligands based on hydrocarbon substituents (CH 3 , phenyl, naphthyl). The effect of the anions was explored using different Ag(I) precursors such as AgPF 6 , AgBF 4 , AgCF 3 SO 3 , or AgNO 3 . A comparison of the crystal structures allowed for the tentative identification of the type of substituents able to induce the formation of CPs having permanent porosity to include a symmetric and moderate steric hindrance on the pyrazolyl moieties (four CH 3 ) and an aromatic and preorganized thioether moiety. An asymmetric steric hindrance on the pyrazole groups led to the formation of more varied structural types. Overall, the most frequently reported structural motifs are the porous hexameric systems and the molecular chains. ■ INTRODUCTIONOver the last three decades, the design of metal-based supramolecular assemblies has become one of the most intense research areas in chemistry and material science 1−7 due to the large number of potential applications of these materials, such as catalysis, 8,9 photochemistry, 10 luminescence, 11 sensing, 12 magnetism, 13,14 gas storage, 15−17 gas purification, 18,19 and medicine. 20 The ligand features and stereoelectronic characteristics of metal ions can control the arrangement of the supramolecular assemblies. The majority of transition metal ions usually exhibit a well-defined geometry (e.g., tetrahedral, square planar, or octahedral). In contrast, the geometry of d 10 metal centers is typically dictated by steric factors, ensuring a greater coordination flexibility. Additional control over the resulting structural arrangement can be achieved by the use of multitopic ligands, which can bridge different metal ions to build flexible network structures. The mutual orientation of the donor atoms defines the ligand geometry as well as the coordinative directionality; the orientation has a profound influence on the overall geometrical s...

The thermodynamic stability of the metallacrown complexes formed by picolinehydroxamic acid (Picha) with Cu(ii), Ni(ii) and Zn(ii) in aqueous solution has been determined by potentiometry, and the speciation models were validated by ESI-MS and UV-visible spectrophotometry. Cu(ii) and Zn(ii) form 12-MC-4 species as the unique metallacrowns present in the solution. While for Cu(ii) the 12-MC-4 is slightly less stable than that obtained with alaninehydroxamic acid (Alaha), the opposite was found for Zn(ii). Moreover, with Cu(ii) unprecedented 15-MC-5 and 18-MC-6 species were identified under ESI-MS conditions. Picha with Ni(ii) forms, in contrast, a 15-MC-5 complex as a unique metallacrown species. Structural studies of the framework of the 12-MC-4 complexes by ab initio methods were also carried out. The results of our investigations allowed us to rationalize not only the different behaviour of Picha in the formation of metallacrowns with the three metal ions, but also the reasons which underpin the strategies for stabilization of these species reported in the literature using ancillary ligands such as pyridine.

A 12-metallacrown-4 (MC) complex was designed and employed as the building block in the synthesis of coordination polymers, one of which is the first permanently porous MC architecture. The connection of the four-fold symmetric MC subunits by Cu(II) nodes led to the formation of 2D layers of metallacrowns. Channels are present in the crystalline architecture, which exhibits permanent porosity manifested in N2 and CO2 uptake capacity.

The paramagnetic one-dimensional H NMR spectra of twelve LnNa(OAc)[12-MC-4] complexes, where Ln is Pr-Yb (except Pm) and Y, are reported. Their solid-state isostructural nature is confirmed in methanol-d solution, as a similar pattern in the H NMR spectra is observed along the series. Notably, a relatively well-resolved spectrum is reported for the Gd complex. The chemical shift data are analyzed using the "all lanthanides" method, and the Fermi contact and pseudo-contact contributions are calculated for the lanthanide-induced shift (LIS). For the Tb-Yb complexes, the pseudo-contact contributions are typically 1 order of magnitude higher than the Fermi contact contributions; however, for the Gd complex, the Fermi contact is the main contribution to the paramagnetic chemical shift. For the methyl protons of the axial acetate (OAc) ligands, the LIS is opposite in sign, with respect to that of the aromatic salicylhydroximate (shi) protons, because of structural rearrangements that occur upon dissociation of the Na cation in solution. The calculated crystal field parameters (B) for the Tb (360 cm), Dy (250 cm), Ho (380 cm), Er (410 cm), Tm (620 cm), and Yb (380 cm) complexes are not constant, likely as a consequence of the inaccuracy of the Bleaney's constants and, to a smaller extent, the small structural changes that occur in solution. Overall, the metallacrown scaffold retains structural integrity and similarity in solution for the entire series; however, small structural features, which do not affect the overall similarity, do likely occur.