The development of solid materials that can be reversibly interconverted by light between forms with different physico-chemical properties is of great interest for separation, catalysis, optoelectronics, holography, mechanical actuation and solar energy conversion. Here, we describe a series of shape-persistent azobenzene tetramers that form porous molecular crystals in their E-configuration, the porosity of which can be tuned by changing the peripheral substituents on the molecule. Efficient E→Z photoisomerization of the azobenzene units takes place in the solid state and converts the crystals into a non-porous amorphous melt phase. Crystallinity and porosity are restored upon Z→E isomerization promoted by visible light irradiation or heating. We demonstrate that the photoisomerization enables reversible on/off switching of optical properties such as birefringence as well as the capture of CO2 from the gas phase. The linear design, structural versatility and synthetic accessibility make this new family of materials potentially interesting for technological applications.

We report a quantitative structure-activity relationship study of a new class of pyrazole-pyridine copper complexes that establishes a clear correlation between the ability to promote copper accumulation and cytotoxicity. Intracellular metal accumulation is maximized when ligand lipophilicity allows the complex to rapidly cross the membrane. Copper and ligand follow different uptake kinetics and reach different intracellular equilibrium concentrations. These results support a model in which the ligand acts as an ionophore for the metal ion, cycling between intra- and extracellular compartments as dissociated or complexed entities. When treating cancer cells with structurally unrelated disulfiram and pyrazole-pyridine copper complexes, as well as with inorganic copper, the same morphological and molecular changes were reproduced, indicating that copper overload is responsible for the cytotoxic effects. Copper-based treatments drive sensitive cancer cells toward paraptotic cell death, a process hallmarked by endoplasmic reticulum stress and massive vacuolization in the absence of apoptotic features. A lack of caspase activation, as observed in copper-treated dying cells, is a consequence of metal-mediated inhibition of caspase-3. Thus, copper acts simultaneously as an endoplasmic reticulum (ER) stress inducer and a caspase-3 inhibitor, forcing the cell into caspase-independent paraptotic death. The establishment of a mechanism of action common to different copper binding agents provides a rationale for the exploitation of copper toxicity as an anticancer tool.

This study reports the structure-activity relationship of a series of 8-hydroxoquinoline derivatives (8-HQs) and focuses on the cytotoxic activity of 5-Cl-7-I-8-HQ (clioquinol, CQ) copper complex (Cu(CQ)). 8-HQs alone cause a dose-dependent loss of viability of the human tumor HeLa and PC3 cells, but the coadministration of copper increases the ligands effects, with extensive cell death occurring in both cell lines. Cytotoxic doses of Cu(CQ) promote intracellular copper accumulation and massive endoplasmic reticulum vacuolization that precede a nonapoptotic (paraptotic) cell death. The cytotoxic effect of Cu(CQ) is reproduced in normal human endothelial cells (HUVEC) at concentrations double those effective in tumor cells, pointing to a potential therapeutic window for Cu(CQ). Finally, the results show that the paraptotic cell death induced by Cu(CQ) does not require nor involve caspases, giving an indication for the current clinical assessment of clioquinol as an antineoplastic agent.

Electrostatic charges patterning along crystalline channels recognize CO2 with high selectivity and promote its fast screwing dynamics through the crystal at one million steps per second, strongly reminiscent of trans-membrane transport in biological channels.

In this study, we show how the combination of metal ions, counter-anions and opportunely functionalized and preorganized ligands gives rise to two distinct supramolecular isomers, coordination polymeric chains and hexameric macrocycles. The hexamers then aggregate to form a cubic structure exhibiting permanent microporosity. The supramolecular assemblies are formed with Ag(+), thioether functionalized bis(pirazolyl)methane ligands and CF3SO3(-)/PF6(-) as the counter-anions. Five different ligands were prepared by modifying the peripheral thioether moiety with naphthyl, methoxy, m-Me, p-Me and F groups (L(SNf), L(SPhOMe), L(SPhm-Me), L(SPhp-Me), and L(SPhF)). Helicoidal coordination polymeric chains are formed with CF3SO3(-) (general formula [Ag(L)]n(CF3SO3)n), whereas macrocyclic hexamers are formed with PF6(-) (general formula [Ag(L)]6(PF6)6). The macrocycles self-assemble into ordered capsules with the shape of a tetrahedron, and the overall framework is sustained by Ag(+)···(PF6(-))···Ag(+) contacts. The capsules generate a highly symmetric structural arrangement, which is characterized by permanent microporosity arising from two distinct types of microporous chambers in the structure. The gas absorption isotherms show that the materials can selectively adsorb CO2 and N2O over CH4 and N2. The modulation of the microporosity of the materials is achieved by the different thioether functionalization of the ligands L(SNf), L(SPhOMe), L(SPhm-Me), and L(SPhF). The diffusion and localization of the gas molecules within the cavities were investigated by 2D (1)H-(13)C solid state NMR on samples loaded with enriched (13)CO2, showing that both types of cavities are accessible to guest molecules from the gas phase.

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.

Channel expansion of flexible molecular architectures endowed with porosity has been proved to be responsive to gas stimuli, such as pressurized CO2, CH4, Xe and hydrocarbons.

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