Metal-organic chains constructed from pre-organized N2S2 donor ligands

Three new N₂S₂ donor ligands 1,1′-((2-(2-(phenylthio)phenylthio)phenyl)methylene)bis(3,5-R-1H-pyrazole), R = H (L^H), R = Me (L^Me), R = i-Pr (L^i-Pr) have been prepared and characterized. These bifunctional ligands incorporate two distinct chelate donor systems, by virtue of the presence of bispyrazole and bisthioether functions. The preferred conformation of these ligands is such that the N₂ and S₂ donor moieties may be oriented in opposite directions, thus favoring the formation of molecular chains when treated with AgBF₄. The X-ray structures of Ag(I) complexes show that, depending on the steric hindrance present on the pyrazole rings, these ligands behave as κ⁴-SSNN-μ bridging tetradentate (when R = H), or κ³-SNN-μ bridging tridentate (when R = Me, i-Pr). Interestingly, [Ag(L^H)]BF₄ crystallizes in the chiral space group P4₁, with the molecular chain that is folded around the 4₁ screw axis.     

An artificial ionophore based on a polyhydroxylated steroid dimer

The Na+ transporting properties of the first member of a new class of artificial ionophores, based on a C2-symmetric polyhydroxylated steroid dimer, are described.     

Effects of allylic and homoallylic substituents on the ring closing metathesis reaction used to synthesise simplified eleuthesides

During the course of our synthetic studies towards simplified eleuthesides, we have found that p-methoxyphenyl (PMP) protected allylic alcohols are compatible with the RCM reaction and can give better yields than the corresponding free allylic alcohols.     

An Efficient RuII–RhIII–RuII Polypyridyl Photocatalyst for Visible‐Light‐Driven Hydrogen Production in Aqueous Solution

The development of multicomponent molecular systems for the photocatalytic reduction of water to hydrogen has experienced considerable growth since the end of the 1970s. Recently, with the aim of improving the efficiency of the catalysis, single‐component photocatalysts have been developed in which the photosensitizer is chemically coupled to the hydrogen‐evolving catalyst in the same molecule through a bridging ligand. Until now, none of these photocatalysts has operated efficiently in pure aqueous solution: a highly desirable medium for energy‐conversion applications. Herein, we introduce a new ruthenium–rhodium polypyridyl complex as the first efficient homogeneous photocatalyst for H₂ production in water with turnover numbers of several hundred. This study also demonstrates unambiguously that the catalytic performance of such systems linked through a nonconjugated bridge is significantly improved as compared to that of a mixture of the separate components.     

Antioxidant activity and chemical composition of three Tunisian Cistus: Cistus monspeliensisCistus villosus and Cistus libanotis☆

The chemical composition of three rockrose Cistus species, Cistus monspeliensis, Cistus libanotis and Cistus villosus, collected in Tunisia, was studied by HPTLC, focusing on the terpenes and phenols constituents. Diterpenes of Cistus are important as the main constituents of the leaf sticky aromatic resin, known as labdanum, which are highly appreciated in perfumery. Polyphenols in the methanolic extracts of each species were identified, quantified as total and as flavonoids and tannins, and tested for antioxidant activity. Diterpenes were evident in C. libanotis and C. monspeliensis, whereas they were practically absent in C. villosus; C. libanotis had higher phenolic amount, whereas antioxidant activities were important, but different according to the following tests: DPPH radical scavenging, conversion of the Fe^3+/ferricyanide complex and inhibition of β-carotene bleaching. The reported data confirm the validity of utilisation of Cistus sp. in marketed herbal products, as well as the relevant presence of diterpenes in species actually not used for labdanum production.     

Synthesis,Characterization, and Biological Evaluation of a Dual-Action Ligand Targeting αvβ3 Integrin and VEGF Receptors

A dual-action ligand targeting both integrin α_Vβ₃ and vascular endothelial growth factor receptors (VEGFRs), was synthesized via conjugation of a cyclic peptidomimetic α_Vβ₃ Arg-Gly-Asp (RGD) ligand with a decapentapeptide. The latter was obtained from a known VEGFR antagonist by acetylation at the Lys13 side chain. Functionalization of the precursor ligands was carried out in solution and in the solid phase, affording two fragments: an alkyne VEGFR ligand and the azide integrin α_Vβ₃ ligand, which were conjugated by click chemistry. Circular dichroism studies confirmed that both the RGD and VEGFR ligand portions of the dual-action compound substantially adopt the biologically active conformation. In vitro binding assays on isolated integrin α_Vβ₃ and VEGFR-1 showed that the dual-action conjugate retains a good level of affinity for both its target receptors, although with one order of magnitude (10/20 times) decrease in potency. The dual-action ligand strongly inhibited the VEGF-induced morphogenesis in Human Umbilical Vein Endothelial Cells (HUVECs). Remarkably, its efficiency in preventing the formation of new blood vessels was similar to that of the original individual ligands, despite the worse affinity towards integrin α_Vβ₃ and VEGFR-1.     

ESR and calculations on electronic structure of phenalenyl and phenalenyl derivative radicals

Calculations on electronic structure of the perinaphthenyl radical and phenalenyl derivative radicals responsible for the composition of the ESR spectrum of marine diesel under heating were performed to obtain support for the experimental ESR results. The parameters calculated were the hyperfine coupling constants (A), which were then used for comparison with the experimental data. The energy‐minimized structures were obtained using the density functional theory method. In all cases, the symmetry system was taken into account in theoretical calculations. The differences between experimental and theoretical values were below 7% for nearest hydrogens in molecules, named hyperfine coupling constant A (first neighbors) and 18% for farthest hydrogens atoms named hyperfine coupling constants A′ (second neighbors), for all structures analyzed. Copyright © 2014 John Wiley & Sons, Ltd.     

Characterization and compatibility study of desloratadine

Desloratadine (DL) is a selective antagonist of the histamine H₁ receptor, which has been widely used to treat allergic symptoms, and stands out from other drugs in this therapeutic class because it does not cause sedative effects. In the present study, the physico-chemical properties of DL were fully characterized using six analytical techniques such as Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TG/DTG), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, Powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The DSC curve shows a sharp endothermic event at 158.4 °C, and the TG/DTG curve presents two decomposition events between 178.4 and 451.9 °C. A compatibility study involving DL and nine pharmaceutical excipients generally used in pharmaceutical formulations was performed. Physical binary mixtures of DL with each excipient were prepared in a 1:1 (w/w) ratio. After preparation, the samples were analyzed immediately and the results reveal solid-state interaction with anhydrous lactose, microcrystalline cellulose, magnesium stearate, and stearic acid.     

Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers

Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the α_vβ₃‐integrin ligand cyclo[DKP–RGD]‐CH₂NH₂ ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified α_Vβ₃‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (α_Vβ₃?) and its subclone CCRF‐CEM α_Vβ₃ (α_Vβ₃+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM α_Vβ₃ versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload.