Salification Controls the In-Vitro Release of Theophylline

Sustained released formulation is the most used strategy to control the efficacy and the adverse reactions of an API (active pharmaceutical ingredient) with a narrow therapeutic index. In this work, we used a different way to tailor the solubility and diffusion of a drug. Salification of Theophylline with Squaric Acid was carried out to better control the absorption of Theophylline after administration. Salification proved to be a winning strategy decreasing the dissolution of the APIs up to 54% with respect to Theophylline. Most importantly, this was accomplished in the first 10 min of the dissolution process, which are the most important for the API administration. Two polymorphs were identified and fully characterized. Theophylline squarate was discovered as trihydrate (SC-XRD) and as a metastable anhydrous form. Indeed, during the Variable Temperature-XRPD experiment, the trihydrate form turned back into the two starting components after losing the three molecules of water. On the other hand, the synthesis of the trihydrate form was observed when a simple mixing of the two starting components were exposed to a high humidity relative percentage (90% RH)

Supramolecular Assemblies in Silver Complexes: Phase Transitions and the Role of the Halogen Bond

Weak interactions (hydrogen bonds, halogen bonds, CH···πand Ï€-πstacking) can play a significant role in the formation of supramolecular assemblies with desired structural features. In this contribution, we report a systematic investigation on how a halogen bond (XB) can modulate the structural arrangement of silver supramolecular complexes. The complexes are composed of X-phenyl(bispyrazolyl)methane (X = Br, I) and I-alkynophenyl(bispyrazolyl)methane ligands functionalized in meta (L3Br, L3I) and para (L4Br, L4I, L4CCI) positions on a phenyl ring with the purpose of providing different directionalities of the X function with respect to the N,N coordination system. The obtained [Ag(L)2]+ moieties show remarkable geometric similarities, and the L4Br, L4I, and L4CCI ligands exhibit the most conserved types of supramolecular arrangement that are sustained by XB. The increased σ-hole in L4CCI with respect to L4I leads to an occurrence of short (and strong) XB interactions with the anions. [Ag(L4I)2]PF6 and [Ag(L4I)2]CF3SO3 are characterized by the presence of three different phases, and the single-crystal evolution from phase-1 (a honeycomb structure with large 1D cavities) to phase-3 (solventless) occurs by a stepwise decrease in the crystallization solvent content, which promotes an increase in XB interactions in the lattice. The present paper aims to provide useful tools for the selection of appropriate components for the use of coordination compounds to build supramolecular systems based on the halogen bond

Projecting the Medium-Term: Outcomes and Errors for GDP Growth

The focus of this paper is the evaluation of a very popular method for potential output estimation and medium-term forecasting - the production function approach - in terms of predictive performance. For this purpose, a forecast evaluation for the three to five years ahead predictions of GDP growth for the individual G7 countries is conducted. To carry out the forecast performance check a particular testing framework is derived that allows the computation of robust test statistics given the specific nature of the generated out-of sample forecasts. In addition, medium-term GDP projections from national and international institutions are examined and it is assessed whether these projections convey a reliable view about future economic developments and whether there is scope for improving their predictive content

Influence of Anions in Silver Supramolecular Frameworks: Structural Characteristics and Sorption Properties

The complexation of a preorganized thioether-functionalized bis(pyrazolyl)methane ligand (L) with silver precursors produces supramolecular structures organized at two hierarchical levels: [AgL]6(X)6 metal–organic cyclic hexamers and their organization in 3D architectures. The cyclic toroidal hexamers of 22–26 Å external diameter are found to be stable already in solution before self-assembly into the crystalline state. In the 3D lattice, the hexameric building block are arranged in different highly symmetric space groups as a function of a variety of anions (cubic Fd3̅ with PF6– or BF4– and rhombohedral R3̅ with CF3SO3– or NO3–) and form cavities with the geometrical shapes of Platonic solids (tetrahedron and octahedron) that can be occupied by a variety of solvent molecules. Upon evacuation, cubic crystals can produce stable frameworks with permanent porosity, which can absorb reversibly several vapors, CO2 and CH4

A real time coincident indicator of the euro area business cycle

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Switchable Dynamics and Flexibility in Gas-absorptive Porous Materials

Our approach is to design porosity in combination with switchable dynamics and flexibility in porous materials for gaining control over gas capture and selectivity. This approach was made possible by fabricating rotor-on-axel molecular struts and tetrahedral building blocks. Ultra-fast molecular rotors as fast as 1011 Hz were engineered in porous crystalline frameworks (molecular crystals, MOFs and mesoporous organosilicas) containing rod-like linkers as amphidynamic elements. The porous frameworks promise access to the control of rotary motion by chemical and physical stimuli. If a gas or a vapor is diffused to the cavities, such as CO 2, iodine and hydrocarbon vapors, rotor dynamics is hampered. In turn, on/off switching produces modulated physical responses. When C-F dipoles were mounted on the rotors, they induced fast oscillating dipoles that interact with an applied electric field. Direct evidence of hostguest interactions at the molecular level were established by 2D solid-state NMR. We achieved the fabrication of swellable porous adamantoid frameworks by the use of highly symmetrical tetrahedral elements and the co-operation of 8 surrounding hydrogen bonds mounted on conformationally flexible groups. The flexibility of the porous crystals manifests itself in response to stimuli of selected gases: CO2, Xe and hexane triggers the enlargement of channel cross-section. The accomodation of CO2 and Xe in the channel chambers was revealed by synchrotron-light XRD, combined with modelling. Xenon dynamics was gathered by 129Xe NMR chemical shift anisotropy profiles, which encode the shape and orientation of each visited cavity. Jump rate and activation energy experienced by exploring Xe atoms were uniquely established. Covalent connection of tetrahedral nodes results in expandable frameworks, especially if 3 instead of all 4 branches are cross-linked: the forth branch can be dedicated to bearing a functional group to catch the gas molecules (CO 2 is retained by –NH2 group by an energy as high as 54 kJ/mol). Moreover, photo-responsive molecular crystals were fabricated by tetrahedral azobenzene tetramers that form porous molecular crystals in their trans configuration. The efficient trans-to-cis photoisomerization converts the crystals into a non-porous phase but crystallinity and porosity are restored upon reverse isomerization promoted by heat. We demonstrated that the photo-isomerization enables reversible on/off switching of optical properties as well as CO2 capture from the gas phase. We thank Cariplo Foundation, Lombardy Region/INSTM Consortium and PRIN 2016. References 1. Acc.Chem.Res.2016,49,1701; 2. Chem.Eur.J. 2017,23,11210; 3. J.Am.Chem.Soc.2014,136,618; 4. Angew.Chem.Int.Ed. 2014,53,1043. 5. Chem.Comm.2017,53,7776; 6. J.Mater.Chem.A2018,6,14231; 7. Chem.Comm. DOI:10.1039/C8CC03951H; 8. NatureChem. 2015,7,634

Oxidative stress induced by copper and iron complexes with 8-hydroxyquinoline derivatives causes paraptotic death of HeLa cancer cells

Here, we report the antiproliferative/cytotoxic properties of 8-hydroxyquinoline (8-HQ) derivatives on HeLa cells in the presence of transition metal ions (Cu2+, Fe3+, Co2+, Ni2+). 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 (Fe3+, Co2+, Ni2+), 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